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Sample records for stop codon readthrough

  1. Readthrough of stop codons by use of aminoglycosides in cells from xeroderma pigmentosum group C patients.

    Science.gov (United States)

    Kuschal, Christiane; Khan, Sikandar G; Enk, Benedikt; DiGiovanna, John J; Kraemer, Kenneth H

    2015-04-01

    Readthrough of premature termination (stop) codons (PTC) is a new approach to treatment of genetic diseases. We recently reported that readthrough of PTC in cells from some xeroderma pigmentosum complementation group C (XP-C) patients could be achieved with the aminoglycosides geneticin or gentamicin. We found that the response depended on several factors including the PTC sequence, its location within the gene and the aminoglycoside used. Here, we extended these studies to investigate the effects of other aminoglycosides that are already on the market. We reasoned that topical treatment could deliver much higher concentrations of drug to the skin, the therapeutic target, and thus increase the therapeutic effect while reducing renal or ototoxicity in comparison with systemic treatment. Our prior clinical studies indicated that only a few percent of normal XPC expression was associated with mild clinical disease. We found minimal cell toxicity in the XP-C cells with several aminoglycosides. We found increased XPC mRNA expression in PTC-containing XP-C cells with G418, paromomycin, neomycin and kanamycin and increased XPC protein expression with G418. We conclude that in selected patients with XP, topical PTC therapy can be investigated as a method of personalized medicine to alleviate their cutaneous symptoms. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  2. Running the Stop Sign: Readthrough of a Premature UAG Termination Signal in the Translation of a Zebrafish (Danio rerio) Taurine Biosynthetic Enzyme.

    Science.gov (United States)

    Larkin, Mary E M; Place, Allen R

    2017-06-03

    The UAG termination codon is generally recognized as the least efficient and least frequently used of the three universal stop codons. This is substantiated by numerous studies in an array of organisms. We present here evidence of a translational readthrough of a mutant nonsense UAG codon in the transcript from the cysteine sulfinic acid decarboxylase ( csad ) gene (ENSDARG00000026348) in zebrafish. The csad gene encodes the terminal enzyme in the taurine biosynthetic pathway. Taurine is a critical amino acid for all animals, playing several essential roles throughout the body, including modulation of the immune system. The sa9430 zebrafish strain (ZDB-ALT-130411-5055) has a point mutation leading to a premature stop codon (UAG) 20 amino acids 5' of the normal stop codon, UGA. Data from immunoblotting, enzyme activity assays, and mass spectrometry provide evidence that the mutant is making a CSAD protein identical to that of the wild-type (XP_009295318.1) in terms of size, activity, and amino acid sequence. UAG readthrough has been described in several species, but this is the first presentation of a case in fish. Also presented are the first data substantiating the ability of a fish CSAD to utilize cysteic acid, an alternative to the standard substrate cysteine sulfinic acid, to produce taurine.

  3. Stop Codon Reassignment in the Wild

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Natalia [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Schwientek, Patrick [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Tripp, H. James [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Rinke, Christian [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Pati, Amrita [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Huntemann, Marcel [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Visel, Axel [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Woyke, Tanja [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Kyrpides, Nikos [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.; Rubin, Edward [Lawrence Berkeley National Lab. (LBNL), Walnut Creek, CA (United States). Dept. of Energy Joint Genome Inst.

    2014-03-21

    Since the discovery of the genetic code and protein translation mechanisms (1), a limited number of variations of the standard assignment between unique base triplets (codons) and their encoded amino acids and translational stop signals have been found in bacteria and phages (2-3). Given the apparent ubiquity of the canonical genetic code, the design of genomically recoded organisms with non-canonical codes has been suggested as a means to prevent horizontal gene transfer between laboratory and environmental organisms (4). It is also predicted that genomically recoded organisms are immune to infection by viruses, under the assumption that phages and their hosts must share a common genetic code (5). This paradigm is supported by the observation of increased resistance of genomically recoded bacteria to phages with a canonical code (4). Despite these assumptions and accompanying lines of evidence, it remains unclear whether differential and non-canonical codon usage represents an absolute barrier to phage infection and genetic exchange between organisms. Our knowledge of the diversity of genetic codes and their use by viruses and their hosts is primarily derived from the analysis of cultivated organisms. Advances in single-cell sequencing and metagenome assembly technologies have enabled the reconstruction of genomes of uncultivated bacterial and archaeal lineages (6). These initial findings suggest that large scale systematic studies of uncultivated microorganisms and viruses may reveal the extent and modes of divergence from the canonical genetic code operating in nature. To explore alternative genetic codes, we carried out a systematic analysis of stop codon reassignments from the canonical TAG amber, TGA opal, and TAA ochre codons in assembled metagenomes from environmental and host-associated samples, single-cell genomes of uncultivated bacteria and archaea, and a collection of phage sequences

  4. RESEARCH ARTICLE Codon usage vis-a-vis start and stop codon ...

    Indian Academy of Sciences (India)

    Prosen

    codon usage at start and stop site showed variation in codon selection in ..... pressure is 8.3%, 0.5% and 18.5% while the influence of other factors, for example natural ..... The codon Adaptation Index--a measure of directional synonymous.

  5. The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients.

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    Amos J Simon

    2010-11-01

    Full Text Available Leukocyte adhesion deficiency 1 (LAD1 is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2 gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.g., gentamicin were reported to partially correct the premature protein termination, by induction of readthrough mechanism.Genetic analysis was performed on 2 LAD1 patients. Expression, functional and immunofluorescence assays of CD18 in the patients were used to determine the in-vivo and in-vitro effects of gentamicin-induced readthrough. A theoretical modeling of the corrected CD18 protein was developed to predict the protein function.We found a novel premature termination codon, C562T (R188X, in exon 6 of the CD18 gene that caused a severe LAD1 phenotype in two unrelated Palestinian children. In-vivo studies on these patients' cells after gentamicin treatment showed abnormal adhesion and chemotactic functions, while in-vitro studies showed mislocalization of the corrected protein to the cytoplasm and not to the cell surface. A theoretical modeling of the corrected CD18 protein suggested that the replacement of the wild type arginine by gentamicin induced tryptophan at the position of the nonsense mutation, although enabled the expression of the entire CD18 protein, this was not sufficient to stabilize the CD18/11 heterodimer at the cell surface.A novel nonsense mutation in the CD18 gene causing a complete absence of CD18 protein and severe LAD1 clinical phenotype is reported. Both in vivo and in vitro treatments with gentamicin resulted in the expression of a corrected full-length dysfunctional or mislocalized CD18 protein. However, while the use of gentamicin increased the expression of CD18, it did not improve leukocyte adhesion and chemotaxis. Moreover, the integrity of the CD18/CD11 complex at the cell surface was impaired, due to abnormal CD18 protein and possibly lack of CD11a

  6. Why has nature invented three stop codons of DNA and only one start codon?

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal; Křížek, P.

    2012-01-01

    Roč. 304, Jul 7 (2012), s. 183-187 ISSN 0022-5193 R&D Projects: GA AV ČR(CZ) IAA100190803 Institutional support: RVO:67985840 Keywords : DNA * RNA * stop codon * synchronization shift * drosophila genome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.351, year: 2012 http://www.sciencedirect.com/science/article/pii/S0022519312001580

  7. Selective forces and mutational biases drive stop codon usage in the human genome: a comparison with sense codon usage.

    Science.gov (United States)

    Trotta, Edoardo

    2016-05-17

    The three stop codons UAA, UAG, and UGA signal the termination of mRNA translation. As a result of a mechanism that is not adequately understood, they are normally used with unequal frequencies. In this work, we showed that selective forces and mutational biases drive stop codon usage in the human genome. We found that, in respect to sense codons, stop codon usage was affected by stronger selective forces but was less influenced by neutral mutational biases. UGA is the most frequent termination codon in human genome. However, UAA was the preferred stop codon in genes with high breadth of expression, high level of expression, AT-rich coding sequences, housekeeping functions, and in gene ontology categories with the largest deviation from expected stop codon usage. Selective forces associated with the breadth and the level of expression favoured AT-rich sequences in the mRNA region including the stop site and its proximal 3'-UTR, but acted with scarce effects on sense codons, generating two regions, upstream and downstream of the stop codon, with strongly different base composition. By favouring low levels of GC-content, selection promoted labile local secondary structures at the stop site and its proximal 3'-UTR. The compositional and structural context favoured by selection was surprisingly emphasized in the class of ribosomal proteins and was consistent with sequence elements that increase the efficiency of translational termination. Stop codons were also heterogeneously distributed among chromosomes by a mechanism that was strongly correlated with the GC-content of coding sequences. In human genome, the nucleotide composition and the thermodynamic stability of stop codon site and its proximal 3'-UTR are correlated with the GC-content of coding sequences and with the breadth and the level of gene expression. In highly expressed genes stop codon usage is compositionally and structurally consistent with highly efficient translation termination signals.

  8. Translation initiation factor elF3 promotes programmed stop codon readthrough

    Czech Academy of Sciences Publication Activity Database

    Beznosková, Petra; Wagner, Susan; Jansen, Myrte Esmeralda; von der Haar, T.; Valášek, Leoš

    2015-01-01

    Roč. 43, č. 10 (2015), s. 5099-5111 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-05394S Institutional support: RVO:61388971 Keywords : EUKARYOTIC RELEASE FACTOR-1 * RNA RECOGNITION MOTIF * TICK FEVER VIRUS Subject RIV: CE - Biochemistry Impact factor: 9.202, year: 2015

  9. Codon usage vis-a-vis start and stop codon context analysis of three ...

    Indian Academy of Sciences (India)

    Prosenjit Paul

    2018-02-20

    Feb 20, 2018 ... Keywords. codon; dinucleotide; selection; mutation; genome. Introduction ..... influence of other factors, for example natural selection, is 91.7%, 99.5% ..... measure of directional synonymous codon usage bias, and its potential ...

  10. Codon usage vis-a-vis start and stop codon context analysis of three ...

    Indian Academy of Sciences (India)

    To understand the variation in genomic composition and its effect on codon usage, we performed the comparative analysis of codon usage and nucleotide usage in the genes of three dicots, Glycine max, Arabidopsis thaliana and Medicago truncatula. The dicot genes were found to be A/T rich and have predominantly ...

  11. Reassigning stop codons via translation termination: How a few eukaryotes broke the dogma.

    Science.gov (United States)

    Alkalaeva, Elena; Mikhailova, Tatiana

    2017-03-01

    The genetic code determines how amino acids are encoded within mRNA. It is universal among the vast majority of organisms, although several exceptions are known. Variant genetic codes are found in ciliates, mitochondria, and numerous other organisms. All revealed genetic codes (standard and variant) have at least one codon encoding a translation stop signal. However, recently two new genetic codes with a reassignment of all three stop codons were revealed in studies examining the protozoa transcriptomes. Here, we discuss this finding and the recent studies of variant genetic codes in eukaryotes. We consider the possible molecular mechanisms allowing the use of certain codons as sense and stop signals simultaneously. The results obtained by studying these amazing organisms represent a new and exciting insight into the mechanism of stop codon decoding in eukaryotes. Also see the video abstract here. © 2017 WILEY Periodicals, Inc.

  12. UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation.

    Science.gov (United States)

    Salvatori, Francesca; Pappadà, Mariangela; Breveglieri, Giulia; D'Aversa, Elisabetta; Finotti, Alessia; Lampronti, Ilaria; Gambari, Roberto; Borgatti, Monica

    2018-05-15

    Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β 0 39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β 0 39 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. We developed a human cellular model of the β 0 39 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts.

  13. Rules of UGA-N decoding by near-cognate tRNAs and analysis of readthrough on short uORFs in yeast

    Czech Academy of Sciences Publication Activity Database

    Beznosková, Petra; Gunišová, Stanislava; Valášek, Leoš Shivaya

    2016-01-01

    Roč. 22, č. 3 (2016), s. 456-466 ISSN 1355-8382 R&D Projects: GA ČR GAP305/12/0480 Institutional support: RVO:61388971 Keywords : programmed stop codon readthrough * termination * eRF1 Subject RIV: CE - Biochemistry Impact factor: 4.605, year: 2016

  14. Analysis of Low Frequency Protein Truncating Stop-Codon Variants and Fasting Concentration of Growth Hormone.

    Directory of Open Access Journals (Sweden)

    Erik Hallengren

    Full Text Available The genetic background of Growth Hormone (GH secretion is not well understood. Mutations giving rise to a stop codon have a high likelihood of affecting protein function.To analyze likely functional stop codon mutations that are associated with fasting plasma concentration of Growth Hormone.We analyzed stop codon mutations in 5451 individuals in the Malmö Diet and Cancer study by genotyping the Illumina Exome Chip. To enrich for stop codon mutations with likely functional effects on protein function, we focused on those disrupting >80% of the predicted amino acid sequence, which were carried by ≥ 10 individuals. Such mutations were related to GH concentration, measured with a high sensitivity assay (hs-GH and, if nominally significant, to GH related phenotypes, using linear regression analysis.Two stop codon mutations were associated with the fasting concentration of hs-GH. rs121909305 (NP_005370.1:p.R93* [Minor Allele Frequency (MAF = 0.8%] in the Myosin 1A gene (MYO1A was associated with a 0.36 (95%CI, 0.04 to 0.54; p=0.02 increment of the standardized value of the natural logarithm of hs-GH per 1 minor allele and rs35699176 (NP_067040.1:p.Q100* in the Zink Finger protein 77 gene (ZNF77 (MAF = 4.8% was associated with a 0.12 (95%CI, 0.02 to 0.22; p = 0.02 increase of hs-GH. The mutated high hs-GH associated allele of MYO1A was related to lower BMI (β-coefficient, -0.22; p = 0.05, waist (β-coefficient, -0.22; p = 0.04, body fat percentage (β-coefficient, -0.23; p = 0.03 and with higher HDL (β-coefficient, 0.23; p = 0.04. The ZNF77 stop codon was associated with height (β-coefficient, 0.11; p = 0.02 but not with cardiometabolic risk factors.We here suggest that a stop codon of MYO1A, disrupting 91% of the predicted amino acid sequence, is associated with higher hs-GH and GH-related traits suggesting that MYO1A is involved in GH metabolism and possibly body fat distribution. However, our results are preliminary and need replication in

  15. Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology.

    Science.gov (United States)

    Jones, Jennifer E; Long, Kristin M; Whitmore, Alan C; Sanders, Wes; Thurlow, Lance R; Brown, Julia A; Morrison, Clayton R; Vincent, Heather; Peck, Kayla M; Browning, Christian; Moorman, Nathaniel; Lim, Jean K; Heise, Mark T

    2017-11-14

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence

  16. Stop codons in the hepatitis B surface proteins are enriched during antiviral therapy and are associated with host cell apoptosis

    International Nuclear Information System (INIS)

    Colledge, Danielle; Soppe, Sally; Yuen, Lilly; Selleck, Lucy; Walsh, Renae; Locarnini, Stephen; Warner, Nadia

    2017-01-01

    Premature stop codons in the hepatitis B virus (HBV) surface protein can be associated with nucleos(t)ide analogue resistance due to overlap of the HBV surface and polymerase genes. The aim of this study was to determine the effect of the replication of three common surface stop codon variants on the hepatocyte. Cell lines were transfected with infectious HBV clones encoding surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of substitutions in the surface proteins. HBsAg was measured by Western blotting. Proliferation and apoptosis were measured using flow cytometry. All three surface stop codon variants were defective in HBsAg secretion. Cells transfected with these variants were less proliferative and had higher levels of apoptosis than those transfected with variants that did not encode surface stop codons. The most cytopathic variant was rtM204I/sW196*. Replication of HBV encoding surface stop codons was toxic to the cell and promoted apoptosis, exacerbating disease progression. - Highlights: •Under normal circumstances, HBV replication is not cytopathic. •Premature stop codons in the HBV surface protein can be selected and enriched during nucleos(t)ide analogue therapy. •Replication of these variants can be cytopathic to the cell and promote apoptosis. •Inadequate antiviral therapy may actually promote disease progression.

  17. Stop codons in the hepatitis B surface proteins are enriched during antiviral therapy and are associated with host cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Colledge, Danielle; Soppe, Sally; Yuen, Lilly; Selleck, Lucy; Walsh, Renae; Locarnini, Stephen, E-mail: stephen.locarnini@mh.org.au; Warner, Nadia

    2017-01-15

    Premature stop codons in the hepatitis B virus (HBV) surface protein can be associated with nucleos(t)ide analogue resistance due to overlap of the HBV surface and polymerase genes. The aim of this study was to determine the effect of the replication of three common surface stop codon variants on the hepatocyte. Cell lines were transfected with infectious HBV clones encoding surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of substitutions in the surface proteins. HBsAg was measured by Western blotting. Proliferation and apoptosis were measured using flow cytometry. All three surface stop codon variants were defective in HBsAg secretion. Cells transfected with these variants were less proliferative and had higher levels of apoptosis than those transfected with variants that did not encode surface stop codons. The most cytopathic variant was rtM204I/sW196*. Replication of HBV encoding surface stop codons was toxic to the cell and promoted apoptosis, exacerbating disease progression. - Highlights: •Under normal circumstances, HBV replication is not cytopathic. •Premature stop codons in the HBV surface protein can be selected and enriched during nucleos(t)ide analogue therapy. •Replication of these variants can be cytopathic to the cell and promote apoptosis. •Inadequate antiviral therapy may actually promote disease progression.

  18. Single nucleotide polymorphisms of Helicobacter pylori dupA that lead to premature stop codons.

    Science.gov (United States)

    Moura, Sílvia B; Costa, Rafaella F A; Anacleto, Charles; Rocha, Gifone A; Rocha, Andreia M C; Queiroz, Dulciene M M

    2012-06-01

     The detection of the putative disease-specific Helicobacter pylori marker duodenal ulcer promoting gene A (dupA) is currently based on PCR detection of jhp0917 and jhp0918 that form the gene. However, mutations that lead to premature stop codons that split off the dupA leading to truncated products cannot be evaluated by PCR. We directly sequence the complete dupA of 75 dupA-positive strains of H. pylori isolated from patients with gastritis (n = 26), duodenal ulcer (n = 29), and gastric carcinoma (n = 20), to search for frame-shifting mutations that lead to stop codon. Thirty-four strains had single nucleotide mutations in dupA that lead to premature stop codon creating smaller products than the predicted 1839 bp product and, for this reason, were considered as dupA-negative. Intact dupA was more frequently observed in strains isolated from duodenal ulcer patients (65.5%) than in patients with gastritis only (46.2%) or with gastric carcinoma (50%). In logistic analysis, the presence of the intact dupA independently associated with duodenal ulcer (OR = 5.06; 95% CI = 1.22-20.96, p = .02).  We propose the primer walking methodology as a simple technique to sequence the gene. When we considered as dupA-positive only those strains that carry dupA gene without premature stop codons, the gene was associated with duodenal ulcer and, therefore, can be used as a marker for this disease in our population. © 2012 Blackwell Publishing Ltd.

  19. Multifaceted regulation of translational readthrough by RNA replication elements in a tombusvirus.

    Directory of Open Access Journals (Sweden)

    Peter A Cimino

    2011-12-01

    Full Text Available Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii mediating cis-preferential replication of viral genomes, and (iii coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.

  20. Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency.

    Science.gov (United States)

    Branchini, A; Ferrarese, M; Lombardi, S; Mari, R; Bernardi, F; Pinotti, M

    2016-10-01

    Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild

  1. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

    Science.gov (United States)

    Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon…

  2. Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma.

    Science.gov (United States)

    Prevost, Luanna B; Smith, Michelle K; Knight, Jennifer K

    2016-01-01

    Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students' ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. © 2016 L. B. Prevost et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Efficient Reassignment of a Frequent Serine Codon in Wild-Type Escherichia coli.

    Science.gov (United States)

    Ho, Joanne M; Reynolds, Noah M; Rivera, Keith; Connolly, Morgan; Guo, Li-Tao; Ling, Jiqiang; Pappin, Darryl J; Church, George M; Söll, Dieter

    2016-02-19

    Expansion of the genetic code through engineering the translation machinery has greatly increased the chemical repertoire of the proteome. This has been accomplished mainly by read-through of UAG or UGA stop codons by the noncanonical aminoacyl-tRNA of choice. While stop codon read-through involves competition with the translation release factors, sense codon reassignment entails competition with a large pool of endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at a number of different serine and leucine codons in wild-type Escherichia coli. Quantitative LC-MS/MS measurements of amino acid incorporation yields carried out in a selected reaction monitoring experiment revealed that the 3-I-Phe abundance at the Ser208AGU codon in superfolder GFP was 65 ± 17%. This method also allowed quantification of other amino acids (serine, 33 ± 17%; phenylalanine, 1 ± 1%; threonine, 1 ± 1%) that compete with 3-I-Phe at both the aminoacylation and decoding steps of translation for incorporation at the same codon position. Reassignments of different serine (AGU, AGC, UCG) and leucine (CUG) codons with the matching tRNA(Pyl) anticodon variants were met with varying success, and our findings provide a guideline for the choice of sense codons to be reassigned. Our results indicate that the 3-iodo-l-phenylalanyl-tRNA synthetase (IFRS)/tRNA(Pyl) pair can efficiently outcompete the cellular machinery to reassign select sense codons in wild-type E. coli.

  4. A novel mutation in the FGB: c.1105C>T turns the codon for amino acid Bβ Q339 into a stop codon causing hypofibrinogenemia.

    Science.gov (United States)

    Marchi, Rita; Brennan, Stephen; Meyer, Michael; Rojas, Héctor; Kanzler, Daniela; De Agrela, Marisela; Ruiz-Saez, Arlette

    2013-03-01

    Routine coagulation tests on a 14year-old male with frequent epistaxis showed a prolonged thrombin time together with diminished functional (162mg/dl) and gravimetric (122mg/dl) fibrinogen concentrations. His father showed similar aberrant results and sequencing of the three fibrinogen genes revealed a novel heterozygous nonsense mutation in the FGB gene c.1105C>T, which converts the codon for residue Bβ 339Q to stop, causing deletion of Bβ chain residues 339-461. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and RP-HPLC (reverse-phase high-pressure liquid chromatography) of purified fibrinogen showed only normal Aα, Bβ, and γ chains, indicating that molecules with the truncated 37,990Da β chain were not secreted into plasma. Functional analysis showed impaired fibrin polymerization, fibrin porosity, and elasticity compared to controls. By laser scanning confocal microscopy the patient's fibers were slightly thinner than normal. Electrospray ionization mass spectrometry (ESI MS) presented normal sialylation of the oligosaccharide chains, and liver function tests showed no evidence of liver dysfunction that might explain the functional abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

    Science.gov (United States)

    Brunelle, Marie-Noëlle; Brakier-Gingras, Léa; Lemay, Guy

    2003-01-01

    Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. PMID:12584361

  6. Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

    Czech Academy of Sciences Publication Activity Database

    Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

    2013-01-01

    Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013

  7. Translation Initiation Factors eIF3 and HCR1 Control Translation Termination and Stop Codon Read-Through in Yeast Cells

    Czech Academy of Sciences Publication Activity Database

    Beznosková, Petra; Cuchalová, Lucie; Wagner, Susan; Shoemaker, Ch. J.; Gunišová, Stanislava; von der Haar, T.; Valášek, Leoš Shivaya

    2013-01-01

    Roč. 9, č. 11 (2013) ISSN 1553-7404 R&D Projects: GA ČR(CZ) GBP305/12/G034 Institutional support: RVO:61388971 Keywords : RNA RECOGNITION MOTIF * MESSENGER-RNA * IN-VIVO Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.167, year: 2013

  8. Introducing COCOS: codon consequence scanner for annotating reading frame changes induced by stop-lost and frame shift variants.

    Science.gov (United States)

    Butkiewicz, Mariusz; Haines, Jonathan L; Bush, William S

    2017-05-15

    Reading frame altering genomic variants can impact gene expression levels and the structure of protein products, thus potentially inducing disease phenotypes. Current annotation approaches report the impact of such variants in the context of altered DNA sequence only; attributes of the resulting transcript, reading frame and translated protein product are not reported. To remedy this shortcoming, we present a new genetic annotation approach termed Codon Consequence Scanner (COCOS). Implemented as an Ensembl variant effect predictor (VEP) plugin, COCOS captures amino acid sequence alterations stemming from variants that produce an altered reading frame, such as stop-lost variants and small insertions and deletions (InDels). To highlight its significance, COCOS was applied to data from the 1000 Genomes Project. Transcripts affected by stop-lost variants introduce a median of 15 amino acids, while InDels have a more extensive impact with a median of 66 amino acids being incorporated. Captured sequence alterations are written out in FASTA format and can be further analyzed for impact on the underlying protein structure. COCOS is available to all users on github: https://github.com/butkiem/COCOS. mariusz.butkiewicz@case.edu. © The Author 2017. Published by Oxford University Press.

  9. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

    DEFF Research Database (Denmark)

    Colagrossi, Luna; Hermans, Lucas E; Salpini, Romina

    2018-01-01

    structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients...

  10. A novel homozygous stop-codon mutation in human HFE responsible for nonsense-mediated mRNA decay.

    Science.gov (United States)

    Padula, Maria Carmela; Martelli, Giuseppe; Larocca, Marilena; Rossano, Rocco; Olivieri, Attilio

    2014-09-01

    HFE-hemochromatosis (HH) is an autosomal disease characterized by excessive iron absorption. Homozygotes for H63D variant, and still less H63D heterozygotes, generally do not express HH phenotype. The data collected in our previous study in the province of Matera (Basilicata, Italy) underlined that some H63D carriers showed altered iron metabolism, without additional factors. In this study, we selected a cohort of 10/22 H63D carriers with severe biochemical iron overload (BIO). Additional analysis was performed for studying HFE exons, exon-intron boundaries, and untranslated regions (UTRs) by performing DNA extraction, PCR amplification and sequencing. The results showed a novel substitution (NM_000410.3:c.847C>T) in a patient exon 4 (GenBankJQ478433); it introduces a premature stop-codon (PTC). RNA extraction and reverse-transcription were also performed. Quantitative real-time PCR was carried out for verifying if our aberrant mRNA is targeted for nonsense-mediated mRNA decay (NMD); we observed that patient HFE mRNA was expressed much less than calibrator, suggesting that the mutated HFE protein cannot play its role in iron metabolism regulation, resulting in proband BIO. Our finding is the first evidence of a variation responsible for a PTC in iron cycle genes. The genotype-phenotype correlation observed in our cases could be related to the additional mutation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. RNA editing makes mistakes in plant mitochondria: editing loses sense in transcripts of a rps19 pseudogene and in creating stop codons in coxI and rps3 mRNAs of Oenothera.

    Science.gov (United States)

    Schuster, W; Brennicke, A

    1991-01-01

    An intact gene for the ribosomal protein S19 (rps19) is absent from Oenothera mitochondria. The conserved rps19 reading frame found in the mitochondrial genome is interrupted by a termination codon. This rps19 pseudogene is cotranscribed with the downstream rps3 gene and is edited on both sides of the translational stop. Editing, however, changes the amino acid sequence at positions that were well conserved before editing. Other strange editings create translational stops in open reading frames coding for functional proteins. In coxI and rps3 mRNAs CGA codons are edited to UGA stop codons only five and three codons, respectively, downstream to the initiation codon. These aberrant editings in essential open reading frames and in the rps19 pseudogene appear to have been shifted to these positions from other editing sites. These observations suggest a requirement for a continuous evolutionary constraint on the editing specificities in plant mitochondria. Images PMID:1762921

  12. Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations.

    Science.gov (United States)

    Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Wolfrum, Uwe

    2014-09-01

    The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30-50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the

  13. Development of a Premature Stop Codon-detection method based on a bacterial two-hybrid system

    Directory of Open Access Journals (Sweden)

    Mayorga Luis S

    2006-09-01

    Full Text Available Abstract Background The detection of Premature Stop Codons (PSCs in human genes is very useful for the genetic diagnosis of different hereditary cancers, e.g. Familial Breast Cancer and Hereditary Non-Polyposis Colorectal Cancer (HNPCC. The products of these PSCs are truncated proteins, detectable in vitro by the Protein Truncation Test and in vivo by using the living translation machinery of yeast or bacteria. These living strategies are based on the construction of recombinant plasmids where the human sequence of interest is inserted upstream of a reporter gene. Although simple, these assays have their limitations. The yeast system requires extensive work to enhance its specificity, and the bacterial systems yield many false results due to translation re-initiation events occurring post PSCs. Our aim was to design a recombinant plasmid useful for detecting PSCs in human genes and resistant to bacterial translation re-initiation interferences. Results A functional recombinant plasmid (pREAL was designed based on a bacterial two-hybrid system. In our design, the in vivo translation of fused fragments of the Bordetella pertussis adenylate cyclase triggers the production of cAMP giving rise to a selectable bacterial phenotype. When a gene of interest is inserted between the two fragments, any PSC inhibits the enzymatic activity of the product, and translation re-initiation events post-PSC yield separated inactive fragments. We demonstrated that the system can accurately detect PSCs in human genes by inserting mutated fragments of the brca1 and msh2 gene. Western Blot assays revealed translation re-initiation events in all the tested colonies, implying that a simpler plasmid would not be resistant to this source of false negative results. The application of the system to a HNPCC family with a nonsense mutation in the msh2 gene correctly diagnosed wild type homozygous and heterozygous patients. Conclusion The developed pREAL is applicable to the

  14. Analysis of four families with the Stickler syndrome by linkage studies. Identification of a new premature stop codon in the COL2A1 gene in a family

    Energy Technology Data Exchange (ETDEWEB)

    Bonaventure, J.; Lasselin, C. [Hopital Necker, Paris (France); Toutain, A. [CHU Bretonneau, Tours (France)] [and others

    1994-09-01

    The Stickler syndrome is an arthro-ophthalmopathy which associates progressive myopia with vitreal degeneration and retinal detachment. Cleft palate, cranio-facial abnormalities, deafness and osteoarthritis are often associated symptoms. Genetic heterogeneity of this autosomal dominant disease was consistent with its large clinical variability. Linkage studies have provided evidence for cosegregation of the disease with COL2A1, the gene coding for type II collagen, in about 50% of the families. Four additional families are reported here. Linkage analyses by using a VNTR located in the 3{prime} region of the gene were achieved. In three families, positive lod scores were obtained with a cumulative maximal value of 3.5 at a recombination fraction of 0. In one of these families, single strand conformation analysis of 25 exons disclosed a new mutation in exon 42. Codon for glutamic acid at position a1-803 was converted into a stop codon. The mutation was detected in DNA samples from all the affected members of the family but not in the unaffected. This result confirms that most of the Stickler syndromes linked to COL2A1 are due to premature stop codons. In a second family, an abnormal SSCP pattern of exon 34 was detected in all the affected individuals. The mutation is likely to correspond to a splicing defect in the acceptor site of intron 33. In one family the disease did not segregate with the COL2A1 locus. Further linkage studies with intragenic dimorphic sites in the COL10A1 gene and highly polymorphic markers close to the COL9A1 locus indicated that this disorder did not result from defects in these two genes.

  15. Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

    DEFF Research Database (Denmark)

    Holch, Anne; Ingmer, Hanne; Licht, Tine Rask

    2013-01-01

    potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10...... % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlAm* (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal...... case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas...

  16. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII

    Science.gov (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C

    2016-01-01

    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  17. A Single Base Pair Mutation Encoding a Premature Stop Codon in the MIS type II receptor is Responsible for Canine Persistent Müllerian Duct Syndrome

    Science.gov (United States)

    Wu, Xiufeng; Wan, Shengqin; Pujar, Shashikant; Haskins, Mark E.; Schlafer, Donald H.; Lee, Mary M.; Meyers-Wallen, Vicki N.

    2008-01-01

    Müllerian Inhibiting Substance (MIS), a secreted glycoprotein in the Transforming Growth Factor-beta (TGF-beta) family of growth factors, mediates regression of the Müllerian ducts during embryonic sex differentiation in males. In Persistent Müllerian Duct Syndrome (PMDS), rather than undergoing involution, the Müllerian ducts persist in males, giving rise to the uterus, Fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited autosomal recessive trait. Previous studies indicated that a defect in the MIS receptor or its downstream signaling pathway was likely to be causative of the canine syndrome. In this study the canine PMDS phenotype and clinical sequelae are described in detail. Affected and unaffected members of this pedigree are genotyped, identifying a single base pair substitution in MISRII that introduces a stop codon in exon 3. The homozygous mutation terminates translation at 80 amino acids, eliminating much of the extracellular domain and the entire transmembrane and intracellular signaling domains. Findings in this model may enable insights to be garnered from correlation of detailed clinical descriptions with molecular defects, which are not otherwise possible in the human syndrome. PMID:18723470

  18. Persistent and transient Listeria monocytogenes strains from retail deli environments vary in their ability to adhere and form biofilms and rarely have inlA premature stop codons.

    Science.gov (United States)

    Wang, Jingjin; Ray, Andrea J; Hammons, Susan R; Oliver, Haley F

    2015-02-01

    Based on recent risk assessments, up to 83% of listeriosis cases from deli meat in the United States are predicted to be from ready-to-eat deli meats contaminated during processing at retail grocery stores. Listeria monocytogenes is known to use sanitizer tolerance and biofilm formation to survive, but interplay of these mechanisms along with virulence potential and persistence mechanisms specific to deli environments had yet to be elucidated. In this study, 442 isolates from food and nonfood contact surfaces in 30 retail delis over 9 months were tested for inlA premature stop codons (PMSCs); inlA encodes InlA, which is necessary to cause listeriosis. A total of 96 isolates, composed of 23 persistent and 73 transient strains, were tested for adhesion and biofilm-forming ability and sanitizer tolerance. Only 10/442 isolates had inlA PMSCs (pdelis with other persistent strains. Most (7/10) PMSC-containing isolates were collected from food contact surfaces (pdelis (p<0.05). Persistent strains had enhanced adhesion on day 1 of a 5-day adhesion-biofilm formation assay. However, there was no significant difference in sanitizer tolerance between persistent and transient strains. Results suggest that foods contaminated with persistent L. monocytogenes strains from the retail environment are (1) likely to have wild-type virulence potential and (2) may persist due to increased adhesion and biofilm formation capacity rather than sanitizer tolerance, thus posing a significant public health risk.

  19. Human apolipoprotein B (apoB) mRNA: Identification of two distinct apoB mRNAs, an mRNA with the apoB-100 sequence and an apoB mRNA containing a premature in-frame translational stop codon, in both liver and intestine

    International Nuclear Information System (INIS)

    Higuchi, K.; Hospattankar, A.V.; Law, S.W.; Meglin, N.; Cortright, J.; Brewer, H.B. Jr.

    1988-01-01

    Human apolipoprotein B (apoB) is present in plasma as two separate isoproteins, designated apoB-100 (512 kDa) and apoB-48 (250 kDa). ApoB is encoded by a single gene on chromosome 2, and a single nuclear mRNA is edited and processed into two separate apoB mRNAs. A 14.1-kilobase apoB mRNA codes for apoB-100, and the second mRNA, which codes for apoB-48, contains a premature stop codon generated by a single base substitution of cytosine to uracil at nucleotide 6,538, which converts the translated CAA codon coding for the amino acid glutamine at residue 2,153 in apoB-100 to a premature in-frame stop codon (UAA). Two 30-base synthetic oligonucleotides, designated apoB-Stop and apoB-Gln, were synthesized containing the complementary sequence to the stop codon (UAA) and glutamine codon (CAA), respectively. The combined results from these studies establish that both human intestine and liver contain the two distinct apoB mRNAs, an mRNA that codes for apoB-100 and an apoB mRNA that contains the premature stop codon, which codes for apoB-48. The premature in-frame stop codon is not tissue specific and is present in both human liver and intestine

  20. Comparative analysis of codon usage bias and codon context patterns between dipteran and hymenopteran sequenced genomes.

    Directory of Open Access Journals (Sweden)

    Susanta K Behura

    Full Text Available BACKGROUND: Codon bias is a phenomenon of non-uniform usage of codons whereas codon context generally refers to sequential pair of codons in a gene. Although genome sequencing of multiple species of dipteran and hymenopteran insects have been completed only a few of these species have been analyzed for codon usage bias. METHODS AND PRINCIPAL FINDINGS: Here, we use bioinformatics approaches to analyze codon usage bias and codon context patterns in a genome-wide manner among 15 dipteran and 7 hymenopteran insect species. Results show that GAA is the most frequent codon in the dipteran species whereas GAG is the most frequent codon in the hymenopteran species. Data reveals that codons ending with C or G are frequently used in the dipteran genomes whereas codons ending with A or T are frequently used in the hymenopteran genomes. Synonymous codon usage orders (SCUO vary within genomes in a pattern that seems to be distinct for each species. Based on comparison of 30 one-to-one orthologous genes among 17 species, the fruit fly Drosophila willistoni shows the least codon usage bias whereas the honey bee (Apis mellifera shows the highest bias. Analysis of codon context patterns of these insects shows that specific codons are frequently used as the 3'- and 5'-context of start and stop codons, respectively. CONCLUSIONS: Codon bias pattern is distinct between dipteran and hymenopteran insects. While codon bias is favored by high GC content of dipteran genomes, high AT content of genes favors biased usage of synonymous codons in the hymenopteran insects. Also, codon context patterns vary among these species largely according to their phylogeny.

  1. Readthrough of long-QT syndrome type 1 nonsense mutations rescues function but alters the biophysical properties of the channel.

    Science.gov (United States)

    Harmer, Stephen C; Mohal, Jagdeep S; Kemp, Duncan; Tinker, Andrew

    2012-05-01

    The nonsense mutations R518X-KCNQ1 and Q530X-KCNQ1 cause LQT1 (long-QT syndrome type 1) and result in a complete loss of I(Ks) channel function. In the present study we attempted to rescue the function of these mutants, in HEK (human embryonic kidney)-293 cells, by promoting readthrough of their PTCs (premature termination codons) using the pharmacological agents G-418, gentamicin and PTC124. Gentamicin and G-418 acted to promote full-length channel protein expression from R518X at 100 μM and from Q530X at 1 mM. In contrast, PTC124 did not, at any dose tested, induce readthrough of either mutant. G-418 (1 mM) treatment also acted to significantly (Pbiophysical properties of the currents produced from R518X, while similar, were not identical with wild-type as the voltage-dependence of activation was significantly (P<0.05) shifted by +25 mV. Overall, these findings indicate that although functional rescue of LQT1 nonsense mutations is possible, it is dependent on the degree of readthrough achieved and the effect on channel function of the amino acid substituted for the PTC. Such considerations will determine the success of future therapies.

  2. A common periodic table of codons and amino acids.

    Science.gov (United States)

    Biro, J C; Benyó, B; Sansom, C; Szlávecz, A; Fördös, G; Micsik, T; Benyó, Z

    2003-06-27

    A periodic table of codons has been designed where the codons are in regular locations. The table has four fields (16 places in each) one with each of the four nucleotides (A, U, G, C) in the central codon position. Thus, AAA (lysine), UUU (phenylalanine), GGG (glycine), and CCC (proline) were placed into the corners of the fields as the main codons (and amino acids) of the fields. They were connected to each other by six axes. The resulting nucleic acid periodic table showed perfect axial symmetry for codons. The corresponding amino acid table also displaced periodicity regarding the biochemical properties (charge and hydropathy) of the 20 amino acids and the position of the stop signals. The table emphasizes the importance of the central nucleotide in the codons and predicts that purines control the charge while pyrimidines determine the polarity of the amino acids. This prediction was experimentally tested.

  3. Immunopurification of the suppressor tRNA dependent rabbit β-globin readthrough protein

    International Nuclear Information System (INIS)

    Hatfield, D.; Thorgeirsson, S.S.; Copeland, T.D.; Oroszlan, S.; Bustin, M.

    1988-01-01

    In mammalian cells, the rabbit β-globin readthrough protein is the only known example of a naturally occurring readthrough protein which does not involve a viral system. To provide an efficient means for its isolation, detection, and study, the authors elicited specific antibodies against this unique protein. The 22 amino acid peptide corresponding to the readthrough portion of this protein was synthesized, coupled to keyhole limpet hemocyanin, and injected into sheep. Specific antibodies to the peptide were produced as demonstrated by the enzyme-linked immunosorbent assay technique and by immunoblotting. The antibodies did not react with globin. The rabbit β-globin readthrough protein was separated from globin and other reticulocyte proteins by polyacrylamide gel electrophoresis and visualized by silver staining or by labeling with [ 35 S] methionine. Incorporation of [ 35 S] methionine into the readthrough protein was significantly enhanced upon addition of an opal suppressor tRNA to reticulocyte lysates. Immunoblotting revealed that the readthrough protein also occurs in lysates without added suppressor tRNA. The antibodies were purified on an affi-gel column which had been coupled with the peptide antigen. The readthrough protein was then purified from reticulocytes by immunoaffinity chromatography and by high-performance liquid chromatography. The results provide conclusive evidence that the β-globin readthrough protein is naturally occurring in rabbit reticulocytes

  4. Atypical RNA Elements Modulate Translational Readthrough in Tobacco Necrosis Virus D.

    Science.gov (United States)

    Newburn, Laura R; White, K Andrew

    2017-04-15

    Tobacco necrosis virus, strain D (TNV-D), is a positive-strand RNA virus in the genus Betanecrovirus and family Tombusviridae The production of its RNA-dependent RNA polymerase, p82, is achieved by translational readthrough. This process is stimulated by an RNA structure that is positioned immediately downstream of the recoding site, termed the readthrough stem-loop (RTSL), and a sequence in the 3' untranslated region of the TNV-D genome, called the distal readthrough element (DRTE). Notably, a base pairing interaction between the RTSL and the DRTE, spanning ∼3,000 nucleotides, is required for enhancement of readthrough. Here, some of the structural features of the RTSL, as well as RNA sequences and structures that flank either the RTSL or DRTE, were investigated for their involvement in translational readthrough and virus infectivity. The results revealed that (i) the RTSL-DRTE interaction cannot be functionally replaced by stabilizing the RTSL structure, (ii) a novel tertiary RNA structure positioned just 3' to the RTSL is required for optimal translational readthrough and virus infectivity, and (iii) these same activities also rely on an RNA stem-loop located immediately upstream of the DRTE. Functional counterparts for the RTSL-proximal structure may also be present in other tombusvirids. The identification of additional distinct RNA structures that modulate readthrough suggests that regulation of this process by genomic features may be more complex than previously appreciated. Possible roles for these novel RNA elements are discussed. IMPORTANCE The analysis of factors that affect recoding events in viruses is leading to an ever more complex picture of this important process. In this study, two new atypical RNA elements were shown to contribute to efficient translational readthrough of the TNV-D polymerase and to mediate robust viral genome accumulation in infections. One of the structures, located close to the recoding site, could have functional

  5. Probable relationship between partitions of the set of codons and the origin of the genetic code.

    Science.gov (United States)

    Salinas, Dino G; Gallardo, Mauricio O; Osorio, Manuel I

    2014-03-01

    Here we study the distribution of randomly generated partitions of the set of amino acid-coding codons. Some results are an application from a previous work, about the Stirling numbers of the second kind and triplet codes, both to the cases of triplet codes having four stop codons, as in mammalian mitochondrial genetic code, and hypothetical doublet codes. Extending previous results, in this work it is found that the most probable number of blocks of synonymous codons, in a genetic code, is similar to the number of amino acids when there are four stop codons, as well as it could be for a primigenious doublet code. Also it is studied the integer partitions associated to patterns of synonymous codons and it is shown, for the canonical code, that the standard deviation inside an integer partition is one of the most probable. We think that, in some early epoch, the genetic code might have had a maximum of the disorder or entropy, independent of the assignment between codons and amino acids, reaching a state similar to "code freeze" proposed by Francis Crick. In later stages, maybe deterministic rules have reassigned codons to amino acids, forming the natural codes, such as the canonical code, but keeping the numerical features describing the set partitions and the integer partitions, like a "fossil numbers"; both kinds of partitions about the set of amino acid-coding codons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma

    Science.gov (United States)

    Grosso, Ana R; Leite, Ana P; Carvalho, Sílvia; Matos, Mafalda R; Martins, Filipa B; Vítor, Alexandra C; Desterro, Joana MP; Carmo-Fonseca, Maria; de Almeida, Sérgio F

    2015-01-01

    Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. DOI: http://dx.doi.org/10.7554/eLife.09214.001 PMID:26575290

  7. Mutations in the codon for a conserved arginine-1563 in the COL4A5 collagen gene in Alport syndrome

    DEFF Research Database (Denmark)

    Zhou, J; Gregory, M C; Hertz, Jens Michael

    1993-01-01

    for arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members....

  8. Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina.

    Science.gov (United States)

    Goldmann, Tobias; Rebibo-Sabbah, Annie; Overlack, Nora; Nudelman, Igor; Belakhov, Valery; Baasov, Timor; Ben-Yosef, Tamar; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin

    2010-12-01

    The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. USH is clinically and genetically heterogeneous, assigned to three clinical types. The most severe type is USH1, characterized by profound inner ear defects and retinitis pigmentosa. Thus far, no effective treatment for the ophthalmic component of USH exists. The p.R31X nonsense mutation in USH1C leads to a disease causing premature termination of gene translation. Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option. Read-through of p.R31X by three commercial, clinically applied aminoglycosides and the synthetic derivative NB30 was validated in vitro, in cell culture, and in retinal explants. Restoration of harmonin functions was monitored in GST pull-downs (scaffold function) and by F-actin bundling analysis in HEK293T cells. Biocompatibility of aminoglycosides was determined in retinal explants by TUNEL assays. In vitro translation and analyses of transfected HEK293T cells revealed a dose-dependent read-through by all aminoglycosides. In addition, gentamicin, paromomycin, and NB30 induced read-through of p.R31X in mouse retinal explants. The read-through of p.R31X restored harmonin protein function. In contrast to all commercial aminoglycosides NB30 showed good biocompatibility. Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation. However, the observed read-through efficiency, along with its significantly reduced toxicity and good biocompatibility, indicate that the novel derivate NB30 represents a better choice than commercial aminoglycosides in a read-through therapy of USH1C and other ocular diseases.

  9. Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons

    DEFF Research Database (Denmark)

    Macvanin, Mirjana; Gonzalez de Valdivia, Ernesto I; Ardell, David H

    2007-01-01

    -peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon......, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin...... resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated...

  10. Codes in the codons: construction of a codon/amino acid periodic table and a study of the nature of specific nucleic acid-protein interactions.

    Science.gov (United States)

    Benyo, B; Biro, J C; Benyo, Z

    2004-01-01

    The theory of "codon-amino acid coevolution" was first proposed by Woese in 1967. It suggests that there is a stereochemical matching - that is, affinity - between amino acids and certain of the base triplet sequences that code for those amino acids. We have constructed a common periodic table of codons and amino acids, where the nucleic acid table showed perfect axial symmetry for codons and the corresponding amino acid table also displayed periodicity regarding the biochemical properties (charge and hydrophobicity) of the 20 amino acids and the position of the stop signals. The table indicates that the middle (2/sup nd/) amino acid in the codon has a prominent role in determining some of the structural features of the amino acids. The possibility that physical contact between codons and amino acids might exist was tested on restriction enzymes. Many recognition site-like sequences were found in the coding sequences of these enzymes and as many as 73 examples of codon-amino acid co-location were observed in the 7 known 3D structures (December 2003) of endonuclease-nucleic acid complexes. These results indicate that the smallest possible units of specific nucleic acid-protein interaction are indeed the stereochemically compatible codons and amino acids.

  11. Translational read-through of a nonsense mutation causing Bartter syndrome.

    Science.gov (United States)

    Cho, Hee Yeon; Lee, Beom Hee; Cheong, Hae Il

    2013-06-01

    Bartter syndrome (BS) is classified into 5 genotypes according to underlying mutant genes and BS III is caused by loss-of-function mutations in the CLCNKB gene encoding for basolateral ClC-Kb. BS III is the most common genotype in Korean patients with BS and W610X is the most common CLCNKB mutation in Korean BS III. In this study, we tested the hypothesis that the CLCNKB W610X mutation can be rescued in vitro using aminoglycoside antibiotics, which are known to induce translational read-through of a nonsense mutation. The CLCNKB cDNA was cloned into a eukaryotic expression vector and the W610X nonsense mutation was generated by site-directed mutagenesis. Cultured polarized MDCK cells were transfected with the vectors, and the read-through was induced using an aminoglycoside derivative, G418. Cellular expression of the target protein was monitored via immunohistochemistry. While cells transfected with the mutant CLCNKB failed to express ClC-Kb, G418 treatment of the cells induced the full-length protein expression, which was localized to the basolateral plasma membranes. It is demonstrated that the W610X mutation in CLCNKB can be a good candidate for trial of translational read-through induction as a therapeutic modality.

  12. Phylogenetic inference with weighted codon evolutionary distances.

    Science.gov (United States)

    Criscuolo, Alexis; Michel, Christian J

    2009-04-01

    We develop a new approach to estimate a matrix of pairwise evolutionary distances from a codon-based alignment based on a codon evolutionary model. The method first computes a standard distance matrix for each of the three codon positions. Then these three distance matrices are weighted according to an estimate of the global evolutionary rate of each codon position and averaged into a unique distance matrix. Using a large set of both real and simulated codon-based alignments of nucleotide sequences, we show that this approach leads to distance matrices that have a significantly better treelikeness compared to those obtained by standard nucleotide evolutionary distances. We also propose an alternative weighting to eliminate the part of the noise often associated with some codon positions, particularly the third position, which is known to induce a fast evolutionary rate. Simulation results show that fast distance-based tree reconstruction algorithms on distance matrices based on this codon position weighting can lead to phylogenetic trees that are at least as accurate as, if not better, than those inferred by maximum likelihood. Finally, a well-known multigene dataset composed of eight yeast species and 106 codon-based alignments is reanalyzed and shows that our codon evolutionary distances allow building a phylogenetic tree which is similar to those obtained by non-distance-based methods (e.g., maximum parsimony and maximum likelihood) and also significantly improved compared to standard nucleotide evolutionary distance estimates.

  13. SHIFT: server for hidden stops analysis in frame-shifted translation.

    Science.gov (United States)

    Gupta, Arun; Singh, Tiratha Raj

    2013-02-23

    Frameshift is one of the three classes of recoding. Frame-shifts lead to waste of energy, resources and activity of the biosynthetic machinery. In addition, some peptides synthesized after frame-shifts are probably cytotoxic which serve as plausible cause for innumerable number of diseases and disorders such as muscular dystrophies, lysosomal storage disorders, and cancer. Hidden stop codons occur naturally in coding sequences among all organisms. These codons are associated with the early termination of translation for incorrect reading frame selection and help to reduce the metabolic cost related to the frameshift events. Researchers have identified several consequences of hidden stop codons and their association with myriad disorders. However the wealth of information available is speckled and not effortlessly acquiescent to data-mining. To reduce this gap, this work describes an algorithmic web based tool to study hidden stops in frameshifted translation for all the lineages through respective genetic code systems. This paper describes SHIFT, an algorithmic web application tool that provides a user-friendly interface for identifying and analyzing hidden stops in frameshifted translation of genomic sequences for all available genetic code systems. We have calculated the correlation between codon usage frequencies and the plausible contribution of codons towards hidden stops in an off-frame context. Markovian chains of various order have been used to model hidden stops in frameshifted peptides and their evolutionary association with naturally occurring hidden stops. In order to obtain reliable and persuasive estimates for the naturally occurring and predicted hidden stops statistical measures have been implemented. This paper presented SHIFT, an algorithmic tool that allows user-friendly exploration, analysis, and visualization of hidden stop codons in frameshifted translations. It is expected that this web based tool would serve as a useful complement for

  14. Genome-wide comparative analysis of codon usage bias and codon context patterns among cyanobacterial genomes.

    Science.gov (United States)

    Prabha, Ratna; Singh, Dhananjaya P; Sinha, Swati; Ahmad, Khurshid; Rai, Anil

    2017-04-01

    With the increasing accumulation of genomic sequence information of prokaryotes, the study of codon usage bias has gained renewed attention. The purpose of this study was to examine codon selection pattern within and across cyanobacterial species belonging to diverse taxonomic orders and habitats. We performed detailed comparative analysis of cyanobacterial genomes with respect to codon bias. Our analysis reflects that in cyanobacterial genomes, A- and/or T-ending codons were used predominantly in the genes whereas G- and/or C-ending codons were largely avoided. Variation in the codon context usage of cyanobacterial genes corresponded to the clustering of cyanobacteria as per their GC content. Analysis of codon adaptation index (CAI) and synonymous codon usage order (SCUO) revealed that majority of genes are associated with low codon bias. Codon selection pattern in cyanobacterial genomes reflected compositional constraints as major influencing factor. It is also identified that although, mutational constraint may play some role in affecting codon usage bias in cyanobacteria, compositional constraint in terms of genomic GC composition coupled with environmental factors affected codon selection pattern in cyanobacterial genomes. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Codon usage bias analysis for the coding sequences of Camellia ...

    African Journals Online (AJOL)

    sunny t

    2016-02-24

    Feb 24, 2016 ... suggested that codon usage bias is driven by selection, particularly for .... For example, as mentioned above, highly expressed genes tend to use fewer ... directional codon bias measure effective number of codons (ENc) was ...

  16. Correlation matrix for quartet codon usage

    CERN Document Server

    Frappat, L; Sorba, Paul

    2005-01-01

    It has been argued that the sum of usage probabilities for codons, belonging to quartets, that have as third nucleotide C or A, is independent of the biological species for vertebrates. The comparison between the theoretical correlation matrix derived from these sum rules and the experimentally computed matrix for 26 species shows a satisfactory agreement. The Shannon entropy, weakly depending on the biological species, gives further support. Suppression of codons containing the dinucleotides CG or AU is put in evidence.

  17. CodonLogo: a sequence logo-based viewer for codon patterns.

    Science.gov (United States)

    Sharma, Virag; Murphy, David P; Provan, Gregory; Baranov, Pavel V

    2012-07-15

    Conserved patterns across a multiple sequence alignment can be visualized by generating sequence logos. Sequence logos show each column in the alignment as stacks of symbol(s) where the height of a stack is proportional to its informational content, whereas the height of each symbol within the stack is proportional to its frequency in the column. Sequence logos use symbols of either nucleotide or amino acid alphabets. However, certain regulatory signals in messenger RNA (mRNA) act as combinations of codons. Yet no tool is available for visualization of conserved codon patterns. We present the first application which allows visualization of conserved regions in a multiple sequence alignment in the context of codons. CodonLogo is based on WebLogo3 and uses the same heuristics but treats codons as inseparable units of a 64-letter alphabet. CodonLogo can discriminate patterns of codon conservation from patterns of nucleotide conservation that appear indistinguishable in standard sequence logos. The CodonLogo source code and its implementation (in a local version of the Galaxy Browser) are available at http://recode.ucc.ie/CodonLogo and through the Galaxy Tool Shed at http://toolshed.g2.bx.psu.edu/.

  18. The C terminus of the polerovirus p5 readthrough domain limits virus infection to the phloem.

    Science.gov (United States)

    Peter, Kari A; Gildow, Frederick; Palukaitis, Peter; Gray, Stewart M

    2009-06-01

    Poleroviruses are restricted to vascular phloem tissues from which they are transmitted by their aphid vectors and are not transmissible mechanically. Phloem limitation has been attributed to the absence of virus proteins either facilitating movement or counteracting plant defense. The polerovirus capsid is composed of two forms of coat protein, the major P3 protein and the minor P3/P5 protein, a translational readthrough of P3. P3/P5 is required for insect transmission and acts in trans to facilitate long-distance virus movement in phloem tissue. Specific potato leafroll virus mutants lacking part or all of the P5 domain moved into and infected nonvascular mesophyll tissue when the source-sink relationship of the plant (Solanum sarrachoides) was altered by pruning, with the progeny virus now being transmissible mechanically. However, in a period of months, a phloem-specific distribution of the virus was reestablished in the absence of aphid transmission. Virus from the new phloem-limited infection showed compensatory mutations that would be expected to restore the production of full-length P3/P5 as well as the loss of mechanical transmissibility. The data support our hypothesis that phloem limitation in poleroviruses presumably does not result from a deficiency in the repertoire of virus genes but rather results from P3/P5 accumulation under selection in the infected plant, with the colateral effect of facilitating transmission by phloem-feeding aphid vectors.

  19. The C Terminus of the Polerovirus P5 Readthrough Domain Limits Virus Infection to the Phloem▿

    Science.gov (United States)

    Peter, Kari A.; Gildow, Frederick; Palukaitis, Peter; Gray, Stewart M.

    2009-01-01

    Poleroviruses are restricted to vascular phloem tissues from which they are transmitted by their aphid vectors and are not transmissible mechanically. Phloem limitation has been attributed to the absence of virus proteins either facilitating movement or counteracting plant defense. The polerovirus capsid is composed of two forms of coat protein, the major P3 protein and the minor P3/P5 protein, a translational readthrough of P3. P3/P5 is required for insect transmission and acts in trans to facilitate long-distance virus movement in phloem tissue. Specific potato leafroll virus mutants lacking part or all of the P5 domain moved into and infected nonvascular mesophyll tissue when the source-sink relationship of the plant (Solanum sarrachoides) was altered by pruning, with the progeny virus now being transmissible mechanically. However, in a period of months, a phloem-specific distribution of the virus was reestablished in the absence of aphid transmission. Virus from the new phloem-limited infection showed compensatory mutations that would be expected to restore the production of full-length P3/P5 as well as the loss of mechanical transmissibility. The data support our hypothesis that phloem limitation in poleroviruses presumably does not result from a deficiency in the repertoire of virus genes but rather results from P3/P5 accumulation under selection in the infected plant, with the colateral effect of facilitating transmission by phloem-feeding aphid vectors. PMID:19297484

  20. Automated design of degenerate codon libraries.

    Science.gov (United States)

    Mena, Marco A; Daugherty, Patrick S

    2005-12-01

    Degenerate codon libraries are frequently used in protein engineering and evolution studies but are often limited to targeting a small number of positions to adequately limit the search space. To mitigate this, codon degeneracy can be limited using heuristics or previous knowledge of the targeted positions. To automate design of libraries given a set of amino acid sequences, an algorithm (LibDesign) was developed that generates a set of possible degenerate codon libraries, their resulting size, and their score relative to a user-defined scoring function. A gene library of a specified size can then be constructed that is representative of the given amino acid distribution or that includes specific sequences or combinations thereof. LibDesign provides a new tool for automated design of high-quality protein libraries that more effectively harness existing sequence-structure information derived from multiple sequence alignment or computational protein design data.

  1. Universality and Shannon entropy of codon usage

    CERN Document Server

    Frappat, L; Sciarrino, A; Sorba, Paul

    2003-01-01

    The distribution functions of the codon usage probabilities, computed over all the available GenBank data, for 40 eukaryotic biological species and 5 chloroplasts, do not follow a Zipf law, but are best fitted by the sum of a constant, an exponential and a linear function in the rank of usage. For mitochondriae the analysis is not conclusive. A quantum-mechanics-inspired model is proposed to describe the observed behaviour. These functions are characterized by parameters that strongly depend on the total GC content of the coding regions of biological species. It is predicted that the codon usage is the same in all exonic genes with the same GC content. The Shannon entropy for codons, also strongly depending on the exonic GC content, is computed.

  2. Hand gesture recognition by analysis of codons

    Science.gov (United States)

    Ramachandra, Poornima; Shrikhande, Neelima

    2007-09-01

    The problem of recognizing gestures from images using computers can be approached by closely understanding how the human brain tackles it. A full fledged gesture recognition system will substitute mouse and keyboards completely. Humans can recognize most gestures by looking at the characteristic external shape or the silhouette of the fingers. Many previous techniques to recognize gestures dealt with motion and geometric features of hands. In this thesis gestures are recognized by the Codon-list pattern extracted from the object contour. All edges of an image are described in terms of sequence of Codons. The Codons are defined in terms of the relationship between maxima, minima and zeros of curvature encountered as one traverses the boundary of the object. We have concentrated on a catalog of 24 gesture images from the American Sign Language alphabet (Letter J and Z are ignored as they are represented using motion) [2]. The query image given as an input to the system is analyzed and tested against the Codon-lists, which are shape descriptors for external parts of a hand gesture. We have used the Weighted Frequency Indexing Transform (WFIT) approach which is used in DNA sequence matching for matching the Codon-lists. The matching algorithm consists of two steps: 1) the query sequences are converted to short sequences and are assigned weights and, 2) all the sequences of query gestures are pruned into match and mismatch subsequences by the frequency indexing tree based on the weights of the subsequences. The Codon sequences with the most weight are used to determine the most precise match. Once a match is found, the identified gesture and corresponding interpretation are shown as output.

  3. Analysis of synonymous codon usage patterns in the genus Rhizobium.

    Science.gov (United States)

    Wang, Xinxin; Wu, Liang; Zhou, Ping; Zhu, Shengfeng; An, Wei; Chen, Yu; Zhao, Lin

    2013-11-01

    The codon usage patterns of rhizobia have received increasing attention. However, little information is available regarding the conserved features of the codon usage patterns in a typical rhizobial genus. The codon usage patterns of six completely sequenced strains belonging to the genus Rhizobium were analysed as model rhizobia in the present study. The relative neutrality plot showed that selection pressure played a role in codon usage in the genus Rhizobium. Spearman's rank correlation analysis combined with correspondence analysis (COA) showed that the codon adaptation index and the effective number of codons (ENC) had strong correlation with the first axis of the COA, which indicated the important role of gene expression level and the ENC in the codon usage patterns in this genus. The relative synonymous codon usage of Cys codons had the strongest correlation with the second axis of the COA. Accordingly, the usage of Cys codons was another important factor that shaped the codon usage patterns in Rhizobium genomes and was a conserved feature of the genus. Moreover, the comparison of codon usage between highly and lowly expressed genes showed that 20 unique preferred codons were shared among Rhizobium genomes, revealing another conserved feature of the genus. This is the first report of the codon usage patterns in the genus Rhizobium.

  4. Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

    Science.gov (United States)

    Münk, Carsten; Beck, Thomas; Zielonka, Jörg; Hotz-Wagenblatt, Agnes; Chareza, Sarah; Battenberg, Marion; Thielebein, Jens; Cichutek, Klaus; Bravo, Ignacio G; O'Brien, Stephen J; Lochelt, Martin; Yuhki, Naoya

    2008-01-01

    Background Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene. Results Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection. Conclusion Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher. PMID:18315870

  5. Codon-optimized antibiotic resistance gene improves efficiency of ...

    Indian Academy of Sciences (India)

    2013-10-01

    Oct 1, 2013 ... transient transformation and cell growth in selective culture were significantly increased by use of fgmR ... Our result shows that similarity in codon usage pattern is an important factor ... Codon adaptation index (CAI) (Sharp.

  6. eCodonOpt: a systematic computational framework for optimizing codon usage in directed evolution experiments

    OpenAIRE

    Moore, Gregory L.; Maranas, Costas D.

    2002-01-01

    We present a systematic computational framework, eCodonOpt, for designing parental DNA sequences for directed evolution experiments through codon usage optimization. Given a set of homologous parental proteins to be recombined at the DNA level, the optimal DNA sequences encoding these proteins are sought for a given diversity objective. We find that the free energy of annealing between the recombining DNA sequences is a much better descriptor of the extent of crossover formation than sequence...

  7. Emergent Rules for Codon Choice Elucidated by Editing Rare Arginine Codons in Escherichia coli

    Science.gov (United States)

    2016-09-20

    the successful 110 CGU con- versions with the 13 optimized codon substitutions to produce strain C123, in which all 123 AGR codons have been removed...culture medium consisted of LBL autoclaved with 1.5% (wt/vol) Bacto Agar (Fisher), containing the same concentrations of antibiotics as necessary. ColE1...controlling the ef- ficiency of protein translation. Cell 141(2):344–354. 15. Li GW (2015) How do bacteria tune translation efficiency? Curr Opin Microbiol

  8. Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

    Directory of Open Access Journals (Sweden)

    Wong Emily HM

    2010-08-01

    Full Text Available Abstract Background The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. Results Relative Synonymous Codon Usage (RSCU values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA. The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus. Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes. Conclusions Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.

  9. Relative codon adaptation: a generic codon bias index for prediction of gene expression.

    Science.gov (United States)

    Fox, Jesse M; Erill, Ivan

    2010-06-01

    The development of codon bias indices (CBIs) remains an active field of research due to their myriad applications in computational biology. Recently, the relative codon usage bias (RCBS) was introduced as a novel CBI able to estimate codon bias without using a reference set. The results of this new index when applied to Escherichia coli and Saccharomyces cerevisiae led the authors of the original publications to conclude that natural selection favours higher expression and enhanced codon usage optimization in short genes. Here, we show that this conclusion was flawed and based on the systematic oversight of an intrinsic bias for short sequences in the RCBS index and of biases in the small data sets used for validation in E. coli. Furthermore, we reveal that how the RCBS can be corrected to produce useful results and how its underlying principle, which we here term relative codon adaptation (RCA), can be made into a powerful reference-set-based index that directly takes into account the genomic base composition. Finally, we show that RCA outperforms the codon adaptation index (CAI) as a predictor of gene expression when operating on the CAI reference set and that this improvement is significantly larger when analysing genomes with high mutational bias.

  10. Preferred and avoided codon pairs in three domains of life

    Directory of Open Access Journals (Sweden)

    Tenson Tanel

    2008-10-01

    Full Text Available Abstract Background Alternative synonymous codons are not used with equal frequencies. In addition, the contexts of codons – neighboring nucleotides and neighboring codons – can have certain patterns. The codon context can influence both translational accuracy and elongation rates. However, it is not known how strong or conserved the codon context preferences in different organisms are. We analyzed 138 organisms (bacteria, archaea and eukaryotes to find conserved patterns of codon pairs. Results After removing the effects of single codon usage and dipeptide biases we discovered a set of neighboring codons for which avoidances or preferences were conserved in all three domains of life. Such biased codon pairs could be divided into subtypes on the basis of the nucleotide patterns that influence the bias. The most frequently avoided type of codon pair was nnUAnn. We discovered that 95.7% of avoided nnUAnn type patterns contain out-frame UAA or UAG triplets on the sense and/or antisense strand. On average, nnUAnn codon pairs are more frequently avoided in ORFeomes than in genomes. Thus we assume that translational selection plays a major role in the avoidance of these codon pairs. Among the preferred codon pairs, nnGCnn was the major type. Conclusion Translational selection shapes codon pair usage in protein coding sequences by rules that are common to all three domains of life. The most frequently avoided codon pairs contain the patterns nnUAnn, nnGGnn, nnGnnC, nnCGCn, GUCCnn, CUCCnn, nnCnnA or UUCGnn. The most frequently preferred codon pairs contain the patterns nnGCnn, nnCAnn or nnUnCn.

  11. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    OpenAIRE

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-01-01

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequen...

  12. The Selective Advantage of Synonymous Codon Usage Bias in Salmonella.

    Directory of Open Access Journals (Sweden)

    Gerrit Brandis

    2016-03-01

    Full Text Available The genetic code in mRNA is redundant, with 61 sense codons translated into 20 different amino acids. Individual amino acids are encoded by up to six different codons but within codon families some are used more frequently than others. This phenomenon is referred to as synonymous codon usage bias. The genomes of free-living unicellular organisms such as bacteria have an extreme codon usage bias and the degree of bias differs between genes within the same genome. The strong positive correlation between codon usage bias and gene expression levels in many microorganisms is attributed to selection for translational efficiency. However, this putative selective advantage has never been measured in bacteria and theoretical estimates vary widely. By systematically exchanging optimal codons for synonymous codons in the tuf genes we quantified the selective advantage of biased codon usage in highly expressed genes to be in the range 0.2-4.2 x 10-4 per codon per generation. These data quantify for the first time the potential for selection on synonymous codon choice to drive genome-wide sequence evolution in bacteria, and in particular to optimize the sequences of highly expressed genes. This quantification may have predictive applications in the design of synthetic genes and for heterologous gene expression in biotechnology.

  13. Stop smoking support programs

    Science.gov (United States)

    Smokeless tobacco - stop smoking programs; Stop smoking techniques; Smoking cessation programs; Smoking cessation techniques ... You can find out about smoking cessation programs from: Your ... Your employer Your local health department The National Cancer ...

  14. Genome-wide analysis of codon usage bias in Ebolavirus.

    Science.gov (United States)

    Cristina, Juan; Moreno, Pilar; Moratorio, Gonzalo; Musto, Héctor

    2015-01-22

    Ebola virus (EBOV) is a member of the family Filoviridae and its genome consists of a 19-kb, single-stranded, negative sense RNA. EBOV is subdivided into five distinct species with different pathogenicities, being Zaire ebolavirus (ZEBOV) the most lethal species. The interplay of codon usage among viruses and their hosts is expected to affect overall viral survival, fitness, evasion from host's immune system and evolution. In the present study, we performed comprehensive analyses of codon usage and composition of ZEBOV. Effective number of codons (ENC) indicates that the overall codon usage among ZEBOV strains is slightly biased. Different codon preferences in ZEBOV genes in relation to codon usage of human genes were found. Highly preferred codons are all A-ending triplets, which strongly suggests that mutational bias is a main force shaping codon usage in ZEBOV. Dinucleotide composition also plays a role in the overall pattern of ZEBOV codon usage. ZEBOV does not seem to use the most abundant tRNAs present in the human cells for most of their preferred codons. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. A codon window in mRNA downstream of the initiation codon where NGG codons give strongly reduced gene expression in Escherichia coli

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2004-01-01

    and GGG, but not GGN or GNG (where N is non-G), are unique since they are associated with a very low gene expression also if located at positions +2, +3 and +5. All codons, including NGG, give a normal gene expression if placed at positions +7. The negative effect by the NGG codons is true for both...

  16. Codon usage and amino acid usage influence genes expression level.

    Science.gov (United States)

    Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

    2018-02-01

    Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

  17. Codon Deviation Coefficient: A novel measure for estimating codon usage bias and its statistical significance

    KAUST Repository

    Zhang, Zhang

    2012-03-22

    Background: Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.Results: Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.Conclusions: As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions. 2012 Zhang et al; licensee BioMed Central Ltd.

  18. Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance

    Directory of Open Access Journals (Sweden)

    Zhang Zhang

    2012-03-01

    Full Text Available Abstract Background Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB. Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis. Results Here we propose a novel measure--Codon Deviation Coefficient (CDC--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance. Conclusions As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.

  19. Synonymous Codon Usage Analysis of Thirty Two Mycobacteriophage Genomes

    Directory of Open Access Journals (Sweden)

    Sameer Hassan

    2009-01-01

    Full Text Available Synonymous codon usage of protein coding genes of thirty two completely sequenced mycobacteriophage genomes was studied using multivariate statistical analysis. One of the major factors influencing codon usage is identified to be compositional bias. Codons ending with either C or G are preferred in highly expressed genes among which C ending codons are highly preferred over G ending codons. A strong negative correlation between effective number of codons (Nc and GC3s content was also observed, showing that the codon usage was effected by gene nucleotide composition. Translational selection is also identified to play a role in shaping the codon usage operative at the level of translational accuracy. High level of heterogeneity is seen among and between the genomes. Length of genes is also identified to influence the codon usage in 11 out of 32 phage genomes. Mycobacteriophage Cooper is identified to be the highly biased genome with better translation efficiency comparing well with the host specific tRNA genes.

  20. Codon adaptation and synonymous substitution rate in diatom plastid genes.

    Science.gov (United States)

    Morton, Brian R; Sorhannus, Ulf; Fox, Martin

    2002-07-01

    Diatom plastid genes are examined with respect to codon adaptation and rates of silent substitution (Ks). It is shown that diatom genes follow the same pattern of codon usage as other plastid genes studied previously. Highly expressed diatom genes display codon adaptation, or a bias toward specific major codons, and these major codons are the same as those in red algae, green algae, and land plants. It is also found that there is a strong correlation between Ks and variation in codon adaptation across diatom genes, providing the first evidence for such a relationship in the algae. It is argued that this finding supports the notion that the correlation arises from selective constraints, not from variation in mutation rate among genes. Finally, the diatom genes are examined with respect to variation in Ks among different synonymous groups. Diatom genes with strong codon adaptation do not show the same variation in synonymous substitution rate among codon groups as the flowering plant psbA gene which, previous studies have shown, has strong codon adaptation but unusually high rates of silent change in certain synonymous groups. The lack of a similar finding in diatoms supports the suggestion that the feature is unique to the flowering plant psbA due to recent relaxations in selective pressure in that lineage.

  1. Complex Codon Usage Pattern and Compositional Features of Retroviruses

    Directory of Open Access Journals (Sweden)

    Sourav RoyChoudhury

    2013-01-01

    Full Text Available Retroviruses infect a wide range of organisms including humans. Among them, HIV-1, which causes AIDS, has now become a major threat for world health. Some of these viruses are also potential gene transfer vectors. In this study, the patterns of synonymous codon usage in retroviruses have been studied through multivariate statistical methods on ORFs sequences from the available 56 retroviruses. The principal determinant for evolution of the codon usage pattern in retroviruses seemed to be the compositional constraints, while selection for translation of the viral genes plays a secondary role. This was further supported by multivariate analysis on relative synonymous codon usage. Thus, it seems that mutational bias might have dominated role over translational selection in shaping the codon usage of retroviruses. Codon adaptation index was used to identify translationally optimal codons among genes from retroviruses. The comparative analysis of the preferred and optimal codons among different retroviral groups revealed that four codons GAA, AAA, AGA, and GGA were significantly more frequent in most of the retroviral genes inspite of some differences. Cluster analysis also revealed that phylogenetically related groups of retroviruses have probably evolved their codon usage in a concerted manner under the influence of their nucleotide composition.

  2. Agutaynen Glottal Stop.

    Science.gov (United States)

    Quakenbush, J. Stephen

    A study investigated the phonemic and morphophonemic patterning of the glottal stop in Agutaynen, a Meso-Philippine language, and some comparison with two northern Philippine languages. Agutaynen glottal stop has as its sole origin a neutralization of contrast rule, the operation of which can be noted in three different linguistic environments.…

  3. The relationship between codon usage bias and cold resistant genes

    International Nuclear Information System (INIS)

    Barozai, M.Y.; Din, M.

    2014-01-01

    This research is based on synonymous codon usage which has been well-known as a feature that affects typical expression level of protein in an organism. Different organisms prefer different codons for same amino acid and this is called Codon Usage Bias (CUB). The codon usage directly affects the level or even direction of changes in protein expression in responses to environmental stimuli. Cold stress is a major abiotic factor that limits the agricultural productivity of plants. In the recent study CUB has been studied in Arabidopsis thaliana cold resistant and housekeeping genes and their homologs in rice (Oryza sativa) to understand the cold stress and housekeeping genes relation with CUB. Six cold resistant and three housekeeping genes in Arabidopsis thaliana and their homologs in rice, were subjected to CUB analysis. The three cold resistant genes (DREB1B, RCI and MYB15) showed more than 50% (52%, 61% and 66% respectively) similar codon usage bias for Arabidopsis thaliana and rice. On the other hand three cold resistant genes (MPK3, ICE1 and ZAT12) showed less than 50% (38%, 38% and 47% respectively) similar codon usage bias for Arabidopsis thaliana and rice. The three housekeeping genes (Actin, Tubulin and Ubiquitin) showed 76% similar codon usage bias for Arabidopsis thaliana and rice. This study will help to manage the plant gene expression through codon optimization under the cold stress. (author)

  4. Nucleotide composition bias and codon usage trends of gene ...

    Indian Academy of Sciences (India)

    2015-06-10

    Jun 10, 2015 ... In a wide variety of organisms, synonymous codons are selected with different ... In addition, a series of GC skew and AT skew data was calculated for codon positions 1, ..... bias from different perspectives. Interestingly .... This study was supported by programme for Changjiang Scholars and Innovative ...

  5. Codon Bias Patterns of E. coli's Interacting Proteins.

    Directory of Open Access Journals (Sweden)

    Maddalena Dilucca

    Full Text Available Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino acid, are used differently across the variety of living organisms. The biological meaning of this phenomenon, known as codon usage bias, is still controversial. In order to shed light on this point, we propose a new codon bias index, CompAI, that is based on the competition between cognate and near-cognate tRNAs during translation, without being tuned to the usage bias of highly expressed genes. We perform a genome-wide evaluation of codon bias for E.coli, comparing CompAI with other widely used indices: tAI, CAI, and Nc. We show that CompAI and tAI capture similar information by being positively correlated with gene conservation, measured by the Evolutionary Retention Index (ERI, and essentiality, whereas, CAI and Nc appear to be less sensitive to evolutionary-functional parameters. Notably, the rate of variation of tAI and CompAI with ERI allows to obtain sets of genes that consistently belong to specific clusters of orthologous genes (COGs. We also investigate the correlation of codon bias at the genomic level with the network features of protein-protein interactions in E.coli. We find that the most densely connected communities of the network share a similar level of codon bias (as measured by CompAI and tAI. Conversely, a small difference in codon bias between two genes is, statistically, a prerequisite for the corresponding proteins to interact. Importantly, among all codon bias indices, CompAI turns out to have the most coherent distribution over the communities of the interactome, pointing to the significance of competition among cognate and near-cognate tRNAs for explaining codon usage adaptation. Notably, CompAI may potentially correlate with translation speed measurements, by accounting for the specific delay induced by wobble-pairing between codons and anticodons.

  6. Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias

    Directory of Open Access Journals (Sweden)

    Sailen Barik

    2017-12-01

    Full Text Available A significant number of proteins in all living species contains amino acid repeats (AARs of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(An] and double [(ABn] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1 One class of amino acid repeats (Class I uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2 The second class (Class II disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons; and finally, (3 In all AARs (including Class I, Class II, and the in-betweens, the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

  7. Amino acid repeats avert mRNA folding through conservative substitutions and synonymous codons, regardless of codon bias.

    Science.gov (United States)

    Barik, Sailen

    2017-12-01

    A significant number of proteins in all living species contains amino acid repeats (AARs) of various lengths and compositions, many of which play important roles in protein structure and function. Here, I have surveyed select homopolymeric single [(A)n] and double [(AB)n] AARs in the human proteome. A close examination of their codon pattern and analysis of RNA structure propensity led to the following set of empirical rules: (1) One class of amino acid repeats (Class I) uses a mixture of synonymous codons, some of which approximate the codon bias ratio in the overall human proteome; (2) The second class (Class II) disregards the codon bias ratio, and appears to have originated by simple repetition of the same codon (or just a few codons); and finally, (3) In all AARs (including Class I, Class II, and the in-betweens), the codons are chosen in a manner that precludes the formation of RNA secondary structure. It appears that the AAR genes have evolved by orchestrating a balance between codon usage and mRNA secondary structure. The insights gained here should provide a better understanding of AAR evolution and may assist in designing synthetic genes.

  8. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

    DEFF Research Database (Denmark)

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

    Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we impl...... codon usage in mammals. Estimates of selection coefficients nevertheless suggest that selection on codon usage is weak and most mutations are nearly neutral. The sensitivity of the analysis on the assumed mutation model is discussed.......Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we...... implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies...

  9. Codon-Precise, Synthetic, Antibody Fragment Libraries Built Using Automated Hexamer Codon Additions and Validated through Next Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Laura Frigotto

    2015-05-01

    Full Text Available We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR in antibody fragment libraries and next generation sequencing (NGS analysis of their quality and diversity.

  10. Luminescent beam stop

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Diane; Morton, Simon A.

    2017-10-25

    This disclosure provides systems, methods, and apparatus related to beam stops. In one aspect, a device comprises a luminescent material, a beam stop plate, and an optical fiber. The luminescent material is a parallelepiped having a first side and a second side that are squares and having a third side that is a rectangle or a square. The first side and the second side are perpendicular to the third side. The beam stop plate is attached to the first side of the luminescent material. The optical fiber has a first end and a second end, with the first end of the optical fiber attached to the third side of the luminescent material.

  11. "Stop Diabetes Now!"

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Diabetes "Stop Diabetes Now!" Past Issues / Fall 2009 Table of Contents ... Tips for Seniors at Risk for Type 2 Diabetes Lifestyle changes that lead to weight loss—such ...

  12. Depression - stopping your medicines

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000570.htm Depression - stopping your medicines To use the sharing features ... prescription medicines you may take to help with depression, anxiety, or pain. Like any medicine, there are ...

  13. Codon based co-occurrence network motifs in human mitochondria

    Directory of Open Access Journals (Sweden)

    Pramod Shinde

    2017-10-01

    Full Text Available The nucleotide polymorphism in human mitochondrial genome (mtDNA tolled by codon position bias plays an indispensable role in human population dispersion and expansion. Herein, we constructed genome-wide nucleotide co-occurrence networks using a massive data consisting of five different geographical regions and around 3000 samples for each region. We developed a powerful network model to describe complex mitochondrial evolutionary patterns between codon and non-codon positions. It was interesting to report a different evolution of Asian genomes than those of the rest which is divulged by network motifs. We found evidence that mtDNA undergoes substantial amounts of adaptive evolution, a finding which was supported by a number of previous studies. The dominance of higher order motifs indicated the importance of long-range nucleotide co-occurrence in genomic diversity. Most notably, codon motifs apparently underpinned the preferences among codon positions for co-evolution which is probably highly biased during the origin of the genetic code. Our analyses manifested that codon position co-evolution is very well conserved across human sub-populations and independently maintained within human sub-populations implying the selective role of evolutionary processes on codon position co-evolution. Ergo, this study provided a framework to investigate cooperative genomic interactions which are critical in underlying complex mitochondrial evolution.

  14. AUG is the only initiation codon in eukaryotes

    Energy Technology Data Exchange (ETDEWEB)

    Sherman, F; McKnight, G; Stewart, J W

    1980-01-01

    An analysis of mutants of the yeast Saccharomyces cerevisiae indicates that AUG is the sole codon capable of initiating translation of iso-1-cytochrome c. This result with yeast and the sequence results of numerous eukaryotic genes indicate that AUG is the only initiation codon in eukaryotes; in contrast, results with Escherichia colia and bacteriophages indicate that both AUG and GUG are initiation codons in prokaryotes. The difference can be explained by the lack of the t/sup 6/ A hypermodified nucleoside (N-(9-(..beta..-D-ribofuranosyl)purin-6-ylcarbamoyl)threonine) in prokaryotic initiator tRNA and its presence in eukaryotic initiator tRNA.

  15. Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

    Science.gov (United States)

    Kegler-Ebo, D M; Docktor, C M; DiMaio, D

    1994-05-11

    We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis.

  16. Comparative analysis of codon usage bias in Crenarchaea and ...

    Indian Academy of Sciences (India)

    ending codons even within the WWY (nucleotide ambiguity code) families in Crenarchaea ...... this work. Acknowledgements. Authors thank Mr Ajit Kumar Sahoo and Ms ... November J. A. 2002 Accounting for background nucleotide com-.

  17. Improved secretory production of calf prochymosin by codon ...

    African Journals Online (AJOL)

    Administrator

    2011-09-12

    Sep 12, 2011 ... results show that codon optimization and disruption of the PMR1 gene synergistically stimulate the secretion of ... With developments in recombinant DNA technology, .... regulated, it is of importance to optimize the variables.

  18. Polymorphism at codon 36 of the p53 gene.

    Science.gov (United States)

    Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

    1994-01-01

    A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

  19. Positive selection for unpreferred codon usage in eukaryotic genomes

    Directory of Open Access Journals (Sweden)

    Galagan James E

    2007-07-01

    Full Text Available Abstract Background Natural selection has traditionally been understood as a force responsible for pushing genes to states of higher translational efficiency, whereas lower translational efficiency has been explained by neutral mutation and genetic drift. We looked for evidence of directional selection resulting in increased unpreferred codon usage (and presumably reduced translational efficiency in three divergent clusters of eukaryotic genomes using a simple optimal-codon-based metric (Kp/Ku. Results Here we show that for some genes natural selection is indeed responsible for causing accelerated unpreferred codon substitution, and document the scope of this selection. In Cryptococcus and to a lesser extent Drosophila, we find many genes showing a statistically significant signal of selection for unpreferred codon usage in one or more lineages. We did not find evidence for this type of selection in Saccharomyces. The signal of positive selection observed from unpreferred synonymous codon substitutions is coincident in Cryptococcus and Drosophila with the distribution of upstream open reading frames (uORFs, another genic feature known to reduce translational efficiency. Functional enrichment analysis of genes exhibiting low Kp/Ku ratios reveals that genes in regulatory roles are particularly subject to this type of selection. Conclusion Through genome-wide scans, we find recent selection for unpreferred codon usage at approximately 1% of genetic loci in a Cryptococcus and several genes in Drosophila. Unpreferred codons can impede translation efficiency, and we find that genes with translation-impeding uORFs are enriched for this selection signal. We find that regulatory genes are particularly likely to be subject to selection for unpreferred codon usage. Given that expression noise can propagate through regulatory cascades, and that low translational efficiency can reduce expression noise, this finding supports the hypothesis that translational

  20. Correcting the bias of empirical frequency parameter estimators in codon models.

    Directory of Open Access Journals (Sweden)

    Sergei Kosakovsky Pond

    2010-07-01

    Full Text Available Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated using nucleotide frequencies observed in a sequence alignment, primarily as a matter of historical convention. In this note, we demonstrate that a popular class of such estimators are biased, and that this bias has an adverse effect on goodness of fit and estimates of substitution rates. We propose a "corrected" empirical estimator that begins with observed nucleotide counts, but accounts for the nucleotide composition of stop codons. We show via simulation that the corrected estimates outperform the de facto standard estimates not just by providing better estimates of the frequencies themselves, but also by leading to improved estimation of other parameters in the evolutionary models. On a curated collection of sequence alignments, our estimators show a significant improvement in goodness of fit compared to the approach. Maximum likelihood estimation of the frequency parameters appears to be warranted in many cases, albeit at a greater computational cost. Our results demonstrate that there is little justification, either statistical or computational, for continued use of the -style estimators.

  1. Codon Usage Bias and Determining Forces in Taenia solium Genome.

    Science.gov (United States)

    Yang, Xing; Ma, Xusheng; Luo, Xuenong; Ling, Houjun; Zhang, Xichen; Cai, Xuepeng

    2015-12-01

    The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome.

  2. Codon Usage Patterns of Tyrosinase Genes in Clonorchis sinensis.

    Science.gov (United States)

    Bae, Young-An

    2017-04-01

    Codon usage bias (CUB) is a unique property of genomes and has contributed to the better understanding of the molecular features and the evolution processes of particular gene. In this study, genetic indices associated with CUB, including relative synonymous codon usage and effective numbers of codons, as well as the nucleotide composition, were investigated in the Clonorchis sinensis tyrosinase genes and their platyhelminth orthologs, which play an important role in the eggshell formation. The relative synonymous codon usage patterns substantially differed among tyrosinase genes examined. In a neutrality analysis, the correlation between GC 12 and GC 3 was statistically significant, and the regression line had a relatively gradual slope (0.218). NC-plot, i.e., GC 3 vs effective number of codons (ENC), showed that most of the tyrosinase genes were below the expected curve. The codon adaptation index (CAI) values of the platyhelminth tyrosinases had a narrow distribution between 0.685/0.714 and 0.797/0.837, and were negatively correlated with their ENC. Taken together, these results suggested that CUB in the tyrosinase genes seemed to be basically governed by selection pressures rather than mutational bias, although the latter factor provided an additional force in shaping CUB of the C. sinensis and Opisthorchis viverrini genes. It was also apparent that the equilibrium point between selection pressure and mutational bias is much more inclined to selection pressure in highly expressed C. sinensis genes, than in poorly expressed genes.

  3. The Effect of Codon Mismatch on the Protein Translation System.

    Directory of Open Access Journals (Sweden)

    Dinglin Zhang

    Full Text Available Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

  4. The Effect of Codon Mismatch on the Protein Translation System.

    Science.gov (United States)

    Zhang, Dinglin; Chen, Danfeng; Cao, Liaoran; Li, Guohui; Cheng, Hong

    2016-01-01

    Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

  5. Distribution of ADAT-Dependent Codons in the Human Transcriptome

    Directory of Open Access Journals (Sweden)

    Àlbert Rafels-Ybern

    2015-07-01

    Full Text Available Nucleotide modifications in the anticodons of transfer RNAs (tRNA play a central role in translation efficiency, fidelity, and regulation of translation, but, for most of these modifications, the details of their function remain unknown. The heterodimeric adenosine deaminases acting on tRNAs (ADAT2-ADAT3, or ADAT are enzymes present in eukaryotes that convert adenine (A to inosine (I in the first anticodon base (position 34 by hydrolytic deamination. To explore the influence of ADAT activity on mammalian translation, we have characterized the human transcriptome and proteome in terms of frequency and distribution of ADAT-related codons. Eight different tRNAs can be modified by ADAT and, once modified, these tRNAs will recognize NNC, NNU and NNA codons, but not NNG codons. We find that transcripts coding for proteins highly enriched in these eight amino acids (ADAT-aa are specifically enriched in NNC, NNU and NNA codons. We also show that the proteins most enriched in ADAT-aa are composed preferentially of threonine, alanine, proline, and serine (TAPS. We propose that the enrichment in ADAT-codons in these proteins is due to the similarities in the codons that correspond to TAPS.

  6. Stopping the unstoppable

    CERN Multimedia

    2002-01-01

    How do you stop two very high energy proton beams circulating in opposite directions around a 27-kilometre ring? The answer is the beam dumps. Two tunnels, pointing in opposite directions, are being constructed at point 6 of the LHC. These will allow the beams to be directed into two large beam dumps housed at the ends of the tunnels.

  7. Ready to stop

    DEFF Research Database (Denmark)

    Molitoris, Joseph; Dribe, Martin

    2016-01-01

    the Roteman Database for Stockholm, Sweden between 1878 and 1926 to examine the association of socioeconomic status and fertility and the adoption of stopping behaviour during the city's transition. Using piecewise constant hazard models and logistic regression, we find that a clear class pattern arises...

  8. The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift site.

    Directory of Open Access Journals (Sweden)

    Suneeth F Mathew

    Full Text Available HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon' contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.

  9. Investigation of RADTRAN Stop Model input parameters for truck stops

    International Nuclear Information System (INIS)

    Griego, N.R.; Smith, J.D.; Neuhauser, K.S.

    1996-01-01

    RADTRAN is a computer code for estimating the risks and consequences as transport of radioactive materials (RAM). RADTRAN was developed and is maintained by Sandia National Laboratories for the US Department of Energy (DOE). For incident-free transportation, the dose to persons exposed while the shipment is stopped is frequently a major percentage of the overall dose. This dose is referred to as Stop Dose and is calculated by the Stop Model. Because stop dose is a significant portion of the overall dose associated with RAM transport, the values used as input for the Stop Model are important. Therefore, an investigation of typical values for RADTRAN Stop Parameters for truck stops was performed. The resulting data from these investigations were analyzed to provide mean values, standard deviations, and histograms. Hence, the mean values can be used when an analyst does not have a basis for selecting other input values for the Stop Model. In addition, the histograms and their characteristics can be used to guide statistical sampling techniques to measure sensitivity of the RADTRAN calculated Stop Dose to the uncertainties in the stop model input parameters. This paper discusses the details and presents the results of the investigation of stop model input parameters at truck stops

  10. Optimally Stopped Optimization

    Science.gov (United States)

    Vinci, Walter; Lidar, Daniel

    We combine the fields of heuristic optimization and optimal stopping. We propose a strategy for benchmarking randomized optimization algorithms that minimizes the expected total cost for obtaining a good solution with an optimal number of calls to the solver. To do so, rather than letting the objective function alone define a cost to be minimized, we introduce a further cost-per-call of the algorithm. We show that this problem can be formulated using optimal stopping theory. The expected cost is a flexible figure of merit for benchmarking probabilistic solvers that can be computed when the optimal solution is not known, and that avoids the biases and arbitrariness that affect other measures. The optimal stopping formulation of benchmarking directly leads to a real-time, optimal-utilization strategy for probabilistic optimizers with practical impact. We apply our formulation to benchmark the performance of a D-Wave 2X quantum annealer and the HFS solver, a specialized classical heuristic algorithm designed for low tree-width graphs. On a set of frustrated-loop instances with planted solutions defined on up to N = 1098 variables, the D-Wave device is between one to two orders of magnitude faster than the HFS solver.

  11. A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

    Science.gov (United States)

    Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

    2017-03-17

    Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

  12. Analysis of amino acid and codon usage in Paramecium bursaria.

    Science.gov (United States)

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-07

    The ciliate Paramecium bursaria harbors the green-alga Chlorella symbionts. We reassembled the P. bursaria transcriptome to minimize falsely fused transcripts, and investigated amino acid and codon usage using the transcriptome data. Surface proteins preferentially use smaller amino acid residues like cysteine. Unusual synonymous codon and amino acid usage in highly expressed genes can reflect a balance between translational selection and other factors. A correlation of gene expression level with synonymous codon or amino acid usage is emphasized in genes down-regulated in symbiont-bearing cells compared to symbiont-free cells. Our results imply that the selection is associated with P. bursaria-Chlorella symbiosis. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. P-value based visualization of codon usage data

    Directory of Open Access Journals (Sweden)

    Fricke Wolfgang

    2006-06-01

    Full Text Available Abstract Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose a multidimensional scaling approach using a novel similarity measure for codon usage tables. Our probabilistic similarity measure is based on P-values derived from the well-known chi-square test for comparison of two distributions. Experimental results on four microbial genomes indicate that the new method is well-suited for the analysis of horizontal gene transfer and translational selection. As compared with the widely-used correspondence analysis, our method did not suffer from outlier sensitivity and showed a better clustering of putative alien genes in most cases.

  14. How Can I Stop Cutting?

    Science.gov (United States)

    ... Educators Search English Español How Can I Stop Cutting? KidsHealth / For Teens / How Can I Stop Cutting? ... in a soft, cozy blanket Substitutes for the Cutting Sensation You'll notice that all the tips ...

  15. A detailed analysis of codon usage patterns and influencing factors in Zika virus.

    Science.gov (United States)

    Singh, Niraj K; Tyagi, Anuj

    2017-07-01

    Recent outbreaks of Zika virus (ZIKV) in Africa, Latin America, Europe, and Southeast Asia have resulted in serious health concerns. To understand more about evolution and transmission of ZIKV, detailed codon usage analysis was performed for all available strains. A high effective number of codons (ENC) value indicated the presence of low codon usage bias in ZIKV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations between nucleotide compositions at third codon positions and ENCs. Correlation analysis between Gravy values, Aroma values and nucleotide compositions at third codon positions also indicated some influence of natural selection. However, the low codon adaptation index (CAI) value of ZIKV with reference to human and mosquito indicated poor adaptation of ZIKV codon usage towards its hosts, signifying that natural selection has a weaker influence than mutational pressure. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent.

  16. Gene expression, nucleotide composition and codon usage bias of genes associated with human Y chromosome.

    Science.gov (United States)

    Choudhury, Monisha Nath; Uddin, Arif; Chakraborty, Supriyo

    2017-06-01

    Analysis of codon usage pattern is important to understand the genetic and evolutionary characteristics of genomes. We have used bioinformatic approaches to analyze the codon usage bias (CUB) of the genes located in human Y chromosome. Codon bias index (CBI) indicated that the overall extent of codon usage bias was low. The relative synonymous codon usage (RSCU) analysis suggested that approximately half of the codons out of 59 synonymous codons were most frequently used, and possessed a T or G at the third codon position. The codon usage pattern was different in different genes as revealed from correspondence analysis (COA). A significant correlation between effective number of codons (ENC) and various GC contents suggests that both mutation pressure and natural selection affect the codon usage pattern of genes located in human Y chromosome. In addition, Y-linked genes have significant difference in GC contents at the second and third codon positions, expression level, and codon usage pattern of some codons like the SPANX genes in X chromosome.

  17. Retroactive Stop Loss Special Pay

    Science.gov (United States)

    Pay (RSLSP), providing $500 for each month/partial month served in stop loss status. Service members served under stop loss must submit a claim for the special pay. Throughout the year, the services have or extension of service, became ineligible to receive retroactive stop loss special pay. There may be

  18. GMSB with light stops

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Antonio [Department of Physics, University of Notre Dame,225 Nieuwland Science Hall, IN 46556, Notre Dame (United States); Theory Division, Physics Department CERN,CH-1211 Geneva 23 (Switzerland); Garcia-Pepin, Mateo [Institut de Física d’Altes Energies, Universitat Autònoma de Barcelona,08193 Bellaterra, Barcelona (Spain); Quiros, Mariano [ICREA at Institut de Física d’Altes Energies, Universitat Autònoma de Barcelona,08193 Bellaterra, Barcelona (Spain)

    2015-08-31

    Gauge mediated supersymmetry breaking (GMSB) is an elegant mechanism to transmit supersymmetry breaking from the hidden to the MSSM observable sector, which solves the supersymmetric flavor problem. However, the smallness of the generated stop mixing requires superheavy stops to reproduce the experimental value of the Higgs mass. A possible way out is to extend the MSSM Higgs sector with singlets and/or triplets providing extra tree-level corrections to the Higgs mass. Singlets will not get any soft mass from GMSB and triplets will contribute to the ρ parameter which could be an issue. In this paper we explore the second possibility by introducing extra supersymmetric triplets with hypercharges Y=(0,±1), with a tree-level custodial SU(2){sub L}⊗SU(2){sub R} global symmetry in the Higgs sector protecting the ρ parameter: a supersymmetric generalization of the Georgi-Machacek model, dubbed as supersymmetric custodial triplet model (SCTM). The renormalization group running from the messenger to the electroweak scale mildly breaks the custodial symmetry. We will present realistic low-scale scenarios (with the NLSP being a Bino-like neutralino or the right-handed stau) based on general (non-minimal) gauge mediation and consistent with all present experimental data. Their main features are: i) Light (∼1 TeV) stops; ii) Exotic couplings (H{sup ±}W{sup ∓}Z and H{sup ±±}W{sup ∓}W{sup ∓}) absent in the MSSM and proportional to the triplets VEV, v{sub Δ}; and, iii) A possible (measurable) universality breaking of the Higgs couplings λ{sub WZ}=r{sub WW}/r{sub ZZ}≠1.

  19. Establishment and comparison of three different codon optimization ...

    African Journals Online (AJOL)

    Yomi

    2012-02-16

    C. elegan). It can raise the n-3/n-6 .... value) could help to judge the numbers of codon types. High level ..... function and health in mammal, especially in .... Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat.

  20. Translational selection on codon usage in the genus Aspergillus.

    Science.gov (United States)

    Iriarte, Andrés; Sanguinetti, Manuel; Fernández-Calero, Tamara; Naya, Hugo; Ramón, Ana; Musto, Héctor

    2012-09-10

    Aspergillus is a genus of mold fungi that includes more than 200 described species. Many members of the group are relevant pathogens and other species are economically important. Only one species has been analyzed for codon usage, and this was performed with a small number of genes. In this paper, we report the codon usage patterns of eight completely sequenced genomes which belong to this genus. The results suggest that selection for translational efficiency and accuracy are the major factors shaping codon usage in all of the species studied so far, and therefore they were active in the last common ancestor of the group. Composition and molecular distances analyses show that highly expressed genes evolve slower at synonymous sites. We identified a conserved core of translationally optimal codons and study the tRNA gene pool in each genome. We found that the great majority of preferred triplets match the respective cognate tRNA with more copies in the respective genome. We discuss the possible scenarios that can explain the observed differences among the species analyzed. Finally we highlight the biotechnological application of this research regarding heterologous protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Genomic composition factors affect codon usage in porcine genome

    African Journals Online (AJOL)

    j.khobondo

    2015-01-28

    Jan 28, 2015 ... The mutational bias hypothesis predicted that genes in the GC-rich regions of the genome ... observed codon divided by its expected frequency at equilibrium. An RSCU value close to 1 indicates lack of bias, ..... study our results points to preferred usage of both C or G and A or T at the synonyms sites as ...

  2. Evaluating codon bias perspective in barbiturase gene using ...

    African Journals Online (AJOL)

    Abdullah

    2014-01-08

    Jan 8, 2014 ... along with codon usage was done to reveal dynamics of gene evolution and expression ... analysis is a potent approach for detecting mutations, selection methods and finding rationale of biased and unbiased gene changes and hence, evolutionary ... in the perception of the molecular basics plus potential.

  3. Establishment and comparison of three different codon optimization ...

    African Journals Online (AJOL)

    C. elegan). It can raise the n-3/n-6 polyunsaturated fatty acids (PUFAs) ratio in mammalian cells. To reveal the impact of different codon optimizations of fat1 gene in influencing the catalysis efficiency of n-6 PUFAs into n-3 PUFAs in mammalian ...

  4. TP53 codon 72 polymorphism in pigmentary phenotypes

    Indian Academy of Sciences (India)

    2012-01-20

    Jan 20, 2012 ... pigmentation by acting as a transcription factor for other genes that are ... skin phototype I-II, burns after exposure to UVR and the development of .... morphisms of TP53 codon 72 with breast carcinoma risk: evidence from ...

  5. Codon usage determines translation rate in Escherichia coli

    DEFF Research Database (Denmark)

    Sørensen, Michael Askvad; Kurland, C G; Pedersen, Steen

    1989-01-01

    We wish to determine whether differences in translation rate are correlated with differences in codon usage or with differences in mRNA secondary structure. We therefore inserted a small DNA fragment in the lacZ gene either directly or flanked by a few frame-shifting bases, leaving the reading fr...

  6. Comparative studies on codon usage pattern of chloroplasts and ...

    Indian Academy of Sciences (India)

    Unknown

    different genomic organization and mutation pressures in nuclear and chloroplast genes. The results of Nc-plots and neutrality plots ... As an important organelle of plants, the chloroplast has its own genomic environment and ... leading to the suggestion that the translation mechanism and patterns of codon usage in ...

  7. Book Review: Stop, Write!

    Directory of Open Access Journals (Sweden)

    Hans Thulesius

    2013-06-01

    Full Text Available This book on writing grounded theory is intended for the empirical GT researcher who wants to pursue his/her research until publication. It is the first book devoted entirely to such a crucial issue as writing grounded theory. Thus, Stop, Write: Writing Grounded Theory, is a practical book that fills a gap in GT methodology. In the first chapter of the book, Dr. Glaser says, “Stop unending conceptualization, unending data coverage, and unending listening to others who would egg you on with additional data, ideas and/or requirements or simply wait too long”. The book teaches the reader how to actually write a grounded theory by “simply” writing up the sorted memos. This requires efficient sorting that is dealt with in chapter two on Sorting Memos, which includes precious repetition from Theoretical Sensitivity (1978. How writing can be done effectively is outlined in chapter three The Working Paper. Then follows chapter four on how to rework the first draft with the different tasks of editing for language and professionalism. Thereafter Dr. Glaser discusses Writing Problems in chapter five where he gives useful guidance on how to overcome writing blocks and problems with supervisors and dissertation committees. The book also deals with publishing and with collaboration as experienced between Barney Glaser and the cofounder of grounded theory, Anselm Strauss.

  8. GMSB with Light Stops

    CERN Document Server

    Delgado, Antonio; Quiros, Mariano

    2015-01-01

    Gauge mediated supersymmetry breaking (GMSB) is an elegant mechanism to transmit supersymmetry breaking from the hidden to the MSSM observable sector, which solves the supersymmetric flavor problem. However the smallness of the generated stop mixing requires superheavy stops to reproduce the experimental value of the Higgs mass. Two possible ways out are: i) To extend GMSB by direct superpotential messenger-MSSM Yukawa couplings to generate sizeable mixing, thus reintroducing the flavor problem; ii) To extend the MSSM Higgs sector with singlets and/or triplets providing extra tree-level corrections to the Higgs mass. Singlets will not get any soft mass from GMSB and triplets will contribute to the $\\rho$ parameter which could be an issue. In this paper we explore the second way by introducing extra supersymmetric triplets with hypercharges $Y=(0,\\pm 1)$, with a tree-level custodial $SU(2)_L\\otimes SU(2)_R$ global symmetry in the Higgs sector protecting the $\\rho$ parameter: a supersymmetric generalization of ...

  9. Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

    Directory of Open Access Journals (Sweden)

    Ivaylo P. Ivanov

    2017-06-01

    Full Text Available Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs in its >700-nucleotide (nt 5′ leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5′ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5′ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression.

  10. One-Stop Dispensing

    DEFF Research Database (Denmark)

    Houlind, Morten Baltzer; McNulty, Helle Bach Ølgaard; Treldal, Charlotte

    2018-01-01

    (1) Objective: To assess hospital medication costs and staff time between One-Stop Dispensing (OSD) and the Traditional Medication System (TMS), and to evaluate patient perspectives on OSD. (2) Methods: The study was conducted at Hvidovre Hospital, University of Copenhagen, Denmark in an elective...... gastric surgery and acute orthopedic surgery department. This study consists of three sub-studies including adult patients able to self-manage medication. In Sub-study 1, staff time used to dispense and administer medication in TMS was assessed. Medication cost and OSD staff time were collected in Sub......-study 2, while patient perspectives were assessed in Sub-study 3. Medication costs with two days of discharge medication were compared between measured OSD cost and simulated TMS cost for the same patients. Measured staff time in OSD was compared to simulated staff time in TMS for the same patients...

  11. Current stopping power analyses

    International Nuclear Information System (INIS)

    Porter, L.E.

    1983-01-01

    Modified Bethe-Bloch stopping power theory permits fairly accurate calculation of energy losses over a broad interval of projectile velocity v = νc insofar as several parameters appearing in the revised Bethe-Bloch formula have been corectly evaluated. Since the parameters cannot in general be ascertained by calculation from first principles, fits of theory to measurement remain the best method of evaluation. The parameters alluded to are: the target mean excitation energy; the shell correction scaling parameters; the composite single free parameter of the Barkas (projectile-z 3 ) effect correction formalism, and the strength of the correction term; the high velocity density effect correction parameter; and the low velocity charge state parameter. These parameters are discussed

  12. Codon-triplet context unveils unique features of the Candida albicans protein coding genome

    Directory of Open Access Journals (Sweden)

    Oliveira José L

    2007-11-01

    Full Text Available Abstract Background The evolutionary forces that determine the arrangement of synonymous codons within open reading frames and fine tune mRNA translation efficiency are not yet understood. In order to tackle this question we have carried out a large scale study of codon-triplet contexts in 11 fungal species to unravel associations or relationships between codons present at the ribosome A-, P- and E-sites during each decoding cycle. Results Our analysis unveiled high bias within the context of codon-triplets, in particular strong preference for triplets of identical codons. We have also identified a surprisingly large number of codon-triplet combinations that vanished from fungal ORFeomes. Candida albicans exacerbated these features, showed an unbalanced tRNA population for decoding its pool of codons and used near-cognate decoding for a large set of codons, suggesting that unique evolutionary forces shaped the evolution of its ORFeome. Conclusion We have developed bioinformatics tools for large-scale analysis of codon-triplet contexts. These algorithms identified codon-triplets context biases, allowed for large scale comparative codon-triplet analysis, and identified rules governing codon-triplet context. They could also detect alterations to the standard genetic code.

  13. Association of sequences in the coat protein/readthrough domain of potato mop-top virus with transmission by Spongospora subterranea.

    Science.gov (United States)

    Reavy, B; Arif, M; Cowan, G H; Torrance, L

    1998-10-01

    A monofungal culture of Spongospora subterranea was unable to acquire and transmit the T isolate of potato mop-top pomovirus (PMTV-T), which has been maintained by manual transmission in the laboratory for 30 years. A recently obtained field isolate (PMTV-S) was efficiently acquired and transmitted by the same fungus culture. Sequence analysis of the readthrough (RT) protein-coding region of PMTV-S showed the presence of an additional 543 nt in the 3' half of the coding region relative to that of PMTV-T. These additional nucleotides preserved the reading frame of the RT protein and inserted 181 amino acids into the RT protein. This was confirmed by a comparison by immunoblotting of the sizes of the RT protein of PMTV-T and other recent isolates of PMTV.

  14. Multiple Evolutionary Selections Involved in Synonymous Codon Usages in the Streptococcus agalactiae Genome.

    Science.gov (United States)

    Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Liu, Zhen-Xing; Hao, Le; Ma, Jiang-Yao; Li, Yu-Gu

    2016-02-24

    Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.

  15. Codon Distribution in Error-Detecting Circular Codes

    Directory of Open Access Journals (Sweden)

    Elena Fimmel

    2016-03-01

    Full Text Available In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick’s hypothesis proved to be wrong, in 1996, Arquès and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self-complementary C3 and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising result, it is shown that the codons can be separated into very few classes (three, or five, or six with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C3 codes to maximal self-complementary circular codes.

  16. Codon Distribution in Error-Detecting Circular Codes.

    Science.gov (United States)

    Fimmel, Elena; Strüngmann, Lutz

    2016-03-15

    In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick's hypothesis proved to be wrong, in 1996, Arquès and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self-complementary C³ and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising) result, it is shown that the codons can be separated into very few classes (three, or five, or six) with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C(3) codes to maximal self-complementary circular codes.

  17. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  18. UDI STOP Femminicidio

    Directory of Open Access Journals (Sweden)

    Giovanna Crivelli

    2014-04-01

    Full Text Available L'UDI, Unione Donne in Italia, ha collaborato con l'Osservatorio dei Processi Comunicativi a un numero monografico della rivista scientifica M@gm@ dal titolo "Violenza maschile e femminicidio". Il numero monografico vuole mettere a disposizione le analisi, l’esperienza e la storia nostra e delle nostre interlocutrici, come contributo al nostro comune lavoro di sensibilizzazione, contrasto alla violenza maschile sulle donne – femminicidio. “UDI STOP femminicidio” è da anni la nostra campagna contro la violenza di genere, la collaborazione con l’Osservatorio dei Processi Comunicativi è parte integrante di questo sforzo. Il primo e dichiarato dei nostri progetti politici è il contrasto alla cultura e al potere ideologico che consente il femminicidio, la subordinazione culturale e sociale, la percezione della donna come oggetto di dominio, la riduzione in schiavitù di tante donne, comprese molte donne prostitute... Sappiamo di non voler tradire una “responsabilità di genere” che deve necessariamente concretizzarsi in tanti “gesti responsabili”, nella lunga pazienza quotidiana che consente la sedimentazione di un cambiamento radicale nelle coscienze. Vogliamo continuare ad essere l’associazione che coniuga insieme la soggettività personale e l'assunzione diretta di responsabilità, della progettualità a lungo termine che non trova “contraddittorio” misurarsi con la solidarietà concreta e quotidiana con le altre donne, nel tentativo di far nascere le nuove maniere di pensare.

  19. The distribution of synonymous codon choice in the translation initiation region of dengue virus.

    Directory of Open Access Journals (Sweden)

    Jian-hua Zhou

    Full Text Available Dengue is the most common arthropod-borne viral (Arboviral illness in humans. The genetic features concerning the codon usage of dengue virus (DENV were analyzed by the relative synonymous codon usage, the effective number of codons and the codon adaptation index. The evolutionary distance between DENV and the natural hosts (Homo sapiens, Pan troglodytes, Aedes albopictus and Aedes aegypti was estimated by a novel formula. Finally, the synonymous codon usage preference for the translation initiation region of this virus was also analyzed. The result indicates that the general trend of the 59 synonymous codon usage of the four genotypes of DENV are similar to each other, and this pattern has no link with the geographic distribution of the virus. The effect of codon usage pattern of Aedes albopictus and Aedes aegypti on the formation of codon usage of DENV is stronger than that of the two primates. Turning to the codon usage preference of the translation initiation region of this virus, some codons pairing to low tRNA copy numbers in the two primates have a stronger tendency to exist in the translation initiation region than those in the open reading frame of DENV. Although DENV, like other RNA viruses, has a high mutation to adapt its hosts, the regulatory features about the synonymous codon usage have been 'branded' on the translation initiation region of this virus in order to hijack the translational mechanisms of the hosts.

  20. Revelation of Influencing Factors in Overall Codon Usage Bias of Equine Influenza Viruses

    Science.gov (United States)

    Bhatia, Sandeep; Sood, Richa; Selvaraj, Pavulraj

    2016-01-01

    Equine influenza viruses (EIVs) of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc) analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse) in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts. PMID:27119730

  1. Codon usage bias in phylum Actinobacteria: relevance to environmental adaptation and host pathogenicity.

    Science.gov (United States)

    Lal, Devi; Verma, Mansi; Behura, Susanta K; Lal, Rup

    2016-10-01

    Actinobacteria are Gram-positive bacteria commonly found in soil, freshwater and marine ecosystems. In this investigation, bias in codon usages of ninety actinobacterial genomes was analyzed by estimating different indices of codon bias such as Nc (effective number of codons), SCUO (synonymous codon usage order), RSCU (relative synonymous codon usage), as well as sequence patterns of codon contexts. The results revealed several characteristic features of codon usage in Actinobacteria, as follows: 1) C- or G-ending codons are used frequently in comparison with A- and U ending codons; 2) there is a direct relationship of GC content with use of specific amino acids such as alanine, proline and glycine; 3) there is an inverse relationship between GC content and Nc estimates, 4) there is low SCUO value (Actinobacteria, extreme GC content and codon bias are driven by mutation rather than natural selection; (2) traits like aerobicity are associated with effective natural selection and therefore low GC content and low codon bias, demonstrating the role of both mutational bias and translational selection in shaping the habitat and phenotype of actinobacterial species. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  2. Analysis of codon usage patterns in Morus notabilis based on genome and transcriptome data.

    Science.gov (United States)

    Wen, Yan; Zou, Ziliang; Li, Hongshun; Xiang, Zhonghuai; He, Ningjia

    2017-06-01

    Codons play important roles in regulating gene expression levels and mRNA half-lives. However, codon usage and related studies in multicellular organisms still lag far behind those in unicellular organisms. In this study, we describe for the first time genome-wide patterns of codon bias in Morus notabilis (mulberry tree), and analyze genome-wide codon usage in 12 other species within the order Rosales. The codon usage of M. notabilis was affected by nucleotide composition, mutation pressure, nature selection, and gene expression level. Translational selection optimal codons were identified and highly expressed genes of M. notabilis tended to use the optimal codons. Genes with higher expression levels have shorter coding region and lower amino acid complexity. Housekeeping genes showed stronger translational selection, which, notably, was not caused by the large differences between the expression level of housekeeping genes and other genes.

  3. Control of ribosome traffic by position-dependent choice of synonymous codons

    DEFF Research Database (Denmark)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

    Messenger RNA (mRNA) encodes a sequence of amino acids by using codons. For most amino acids, there are multiple synonymous codons that can encode the amino acid. The translation speed can vary from one codon to another, thus there is room for changing the ribosome speed while keeping the amino...... acid sequence and hence the resulting protein. Recently, it has been noticed that the choice of the synonymous codon, via the resulting distribution of slow- and fast-translated codons, affects not only on the average speed of one ribosome translating the mRNA but also might have an effect on nearby...... ribosomes by affecting the appearance of 'traffic jams' where multiple ribosomes collide and form queues. To test this 'context effect' further, we here investigate the effect of the sequence of synonymous codons on the ribosome traffic by using a ribosome traffic model with codon-dependent rates, estimated...

  4. Analysis of transcriptome data reveals multifactor constraint on codon usage in Taenia multiceps.

    Science.gov (United States)

    Huang, Xing; Xu, Jing; Chen, Lin; Wang, Yu; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2017-04-20

    Codon usage bias (CUB) is an important evolutionary feature in genomes that has been widely observed in many organisms. However, the synonymous codon usage pattern in the genome of T. multiceps remains to be clarified. In this study, we analyzed the codon usage of T. multiceps based on the transcriptome data to reveal the constraint factors and to gain an improved understanding of the mechanisms that shape synonymous CUB. Analysis of a total of 8,620 annotated mRNA sequences from T. multiceps indicated only a weak codon bias, with mean GC and GC3 content values of 49.29% and 51.43%, respectively. Our analysis indicated that nucleotide composition, mutational pressure, natural selection, gene expression level, amino acids with grand average of hydropathicity (GRAVY) and aromaticity (Aromo) and the effective selection of amino-acids all contributed to the codon usage in T. multiceps. Among these factors, natural selection was implicated as the major factor affecting the codon usage variation in T. multiceps. The codon usage of ribosome genes was affected mainly by mutations, while the essential genes were affected mainly by selection. In addition, 21codons were identified as "optimal codons". Overall, the optimal codons were GC-rich (GC:AU, 41:22), and ended with G or C (except CGU). Furthermore, different degrees of variation in codon usage were found between T. multiceps and Escherichia coli, yeast, Homo sapiens. However, little difference was found between T. multiceps and Taenia pisiformis. In this study, the codon usage pattern of T. multiceps was analyzed systematically and factors affected CUB were also identified. This is the first study of codon biology in T. multiceps. Understanding the codon usage pattern in T. multiceps can be helpful for the discovery of new genes, molecular genetic engineering and evolutionary studies.

  5. Synonymous codon ordering: a subtle but prevalent strategy of bacteria to improve translational efficiency.

    Directory of Open Access Journals (Sweden)

    Zhu-Qing Shao

    Full Text Available BACKGROUND: In yeast coding sequences, once a particular codon has been used, subsequent occurrence of the same amino acid tends to use codons sharing the same tRNA. Such a phenomenon of co-tRNA codons pairing bias (CTCPB is also found in some other eukaryotes but it is not known whether it occurs in prokaryotes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we focused on a total of 773 bacterial genomes to investigate their synonymous codon pairing preferences. After calculating the actual frequencies of synonymous codon pairs and comparing them with their expected values, we detected an obvious pairing bias towards identical codon pairs. This seems consistent with the previously reported CTCPB phenomenon, since identical codons are certainly read by the same tRNA. However, among co-tRNA but non-identical codon pairs, only 22 were often found overrepresented, suggesting that many co-tRNA codons actually do not preferentially pair together in prokaryotes. Therefore, the previously reported co-tRNA codons pairing rule needs to be more rigorously defined. The affinity differences between a tRNA anticodon and its readable codons should be taken into account. Moreover, both within-gene-shuffling tests and phylogenetic analyses support the idea that translational selection played an important role in shaping the observed synonymous codon pairing pattern in prokaryotes. CONCLUSIONS: Overall, a high level of synonymous codon pairing bias was detected in 73% investigated bacterial species, suggesting the synonymous codon ordering strategy has been prevalently adopted by prokaryotes to improve their translational efficiencies. The findings in this study also provide important clues to better understand the complex dynamics of translational process.

  6. Nitrogen Research Programme STOP

    International Nuclear Information System (INIS)

    Erisman, J.W.; Van der Eerden, L.

    2000-01-01

    Nitrogen pollution is one of the main threats to the environment now in the Netherlands as well as other parts of Europe. In order to address the main gaps on the issues of nitrogen pollution related to the local scale, the Ministries of Housing, Physical Planning and Environment (VROM) and of Agriculture, Nature Management and Fisheries (LNV) have initiated a research programme, the Dutch Nitrogen Research Programme (STOP), which aims to provide a scientific basis to develop and implement policy on a local scale for the realisation and conservation of the EHS ('Dutch Mainframe of Natural Landscapes'). The results of the programme show that the description of emissions from manure in the field is difficult to describe and show large uncertainties. On the contrary, emissions from housings could be modelled well, if local actual data were available. The OPS model to describe the dispersion and deposition was evaluated with the measurements and the limitations were quantified. It appears that the model works well on the long term, whereas on the short term (hours) and short distance (tenths of meters) there is large uncertainty, especially in complex terrain. Critical loads for nitrogen for ecosystems were evaluated. Furthermore, the effect of management options was quantified. A method to determine critical loads as a function of soil conditions, such as acidification and water availability was derived. This resulted in a combination of the soil model SMART and the so-called 'nature planner' (Natuurplanner). It was concluded that the combination of SMART, the nature planner and OPS provide a good tool to develop and support policy on the local scale. 4 refs

  7. BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

    DEFF Research Database (Denmark)

    Meeks, Huong D; Song, Honglin; Michailidou, Kyriaki

    2016-01-01

    3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1...... and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.......43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. CONCLUSIONS: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2...

  8. BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

    NARCIS (Netherlands)

    H.D. Meeks (Huong D.); H. Song (Honglin); K. Michailidou (Kyriaki); M.K. Bolla (Manjeet); J. Dennis (Joe); Q. Wang (Qing); D. Barrowdale (Daniel); D. Frost (Debra); L. McGuffog (Lesley); S.D. Ellis (Steve); B. Feng (Bingjian); S.S. Buys (Saundra); J.L. Hopper (John); M.C. Southey (Melissa); A. Tesoriero (Andrea); M. James (Margaret); F. Bruinsma (Fiona); I. Campbell (Ian); A. Broeks (Annegien); M.K. Schmidt (Marjanka); F.B.L. Hogervorst (Frans); M.W. Beckmann (Matthias); P.A. Fasching (Peter); O. Fletcher (Olivia); N. Johnson (Nichola); E.J. Sawyer (Elinor); E. Riboli (Elio); S. Banerjee (Susana); U. Menon (Usha); I. Tomlinson (Ian); B. Burwinkel (Barbara); U. Hamann (Ute); F. Marme (Federick); A. Rudolph (Anja); R. Janavicius (Ramunas); L. Tihomirova (Laima); N. Tung (Nadine); J. Garber (Judy); D. Cramer (Daniel); K.L. Terry (Kathryn); E.M. Poole (Elizabeth); S. Tworoger (Shelley); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); A.K. Godwin (Andrew K.); P. Guénel (Pascal); T. Truong (Thérèse); D. Stoppa-Lyonnet (Dominique); F. Damiola (Francesca); S. Mazoyer (Sylvie); O. Sinilnikova (Olga); C. Isaacs (Claudine); C. Maugard; S.E. Bojesen (Stig); H. Flyger (Henrik); A-M. Gerdes (Anne-Marie); T.V.O. Hansen (Thomas); A. Jensen (Allen); M. Kjaer (Michael); C.K. Høgdall (Claus); E. Høgdall (Estrid); I.S. Pedersen (Inge Sokilde); M. Thomassen (Mads); J. Benítez (Javier); A. González-Neira (Anna); A. Osorio (Ana); M.D.L. Hoya (Miguel De La); P.P. Segura (Pedro Perez); O. Díez (Orland); C. Lazaro (Conxi); J. Brunet (Joan); H. Anton-Culver (Hoda); L. Eunjung (Lee); E.M. John (Esther); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); D. Castillo (Danielle); J.N. Weitzel (Jeffrey); P.A. Ganz (Patricia A.); R. Nussbaum (Robert); S. Chan (Salina); B.Y. Karlan (Beth Y.); K.J. Lester (Kathryn); A. Wu (Anna); S.A. Gayther (Simon); S.J. Ramus (Susan); W. Sieh (Weiva); A.S. Whittermore (Alice S.); A.N.A. Monteiro (Alvaro N.A.); C. Phelan (Catherine); M.B. Terry (Mary Beth); M. Piedmonte (Marion); K. Offit (Kenneth); M. Robson (Mark); D.A. Levine (Douglas); K.B. Moysich (Kirsten B.); R. Cannioto (Rikki); S.H. Olson (Sara); M.B. Daly (Mary B.); K.L. Nathanson (Katherine); S.M. Domchek (Susan); K.H. Lu (Karen); D. Liang (Dong); M.A.T. Hildebrant (Michelle A.T.); R.B. Ness (Roberta); F. Modugno (Francesmary); L. Pearce (Leigh); M.T. Goodman (Marc T.); P.J. Thompson (Pamela J.); H. Brenner (Hermann); K. Butterbach (Katja); A. Meindl (Alfons); E. Hahnen (Eric); B. Wapenschmidt (Barbara); H. Brauch (Hiltrud); T. Brüning (Thomas); C. Blomqvist (Carl); S. Khan (Sofia); H. Nevanlinna (Heli); L.M. Pelttari (Liisa); K. Aittomäki (Kristiina); R. Butzow (Ralf); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); J. Rantala (Johanna); V-M. Kosma (Veli-Matti); A. Mannermaa (Arto); D. Lambrechts (Diether); P. Neven (Patrick); K.B.M. Claes (Kathleen B.M.); T. Van Maerken (Tom); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); P.U. Heitz; R. Varon-Mateeva (Raymonda); P. Peterlongo (Paolo); P. Radice (Paolo); A. Viel (Alessandra); M. Barile (Monica); B. Peissel (Bernard); S. Manoukian (Siranoush); M. Montagna (Marco); C. Oliani (Cristina); A. Peixoto (Ana); P.J. Teixeira; A. Collavoli (Anita); B. Hallberg (Boubou); J.E. Olson (Janet); E.L. Goode (Ellen L.); S.N. Hart (Steven N.); H. Shimelis (Hermela); J.M. Cunningham (Julie); G.G. Giles (Graham); R.L. Milne (Roger); S. Healey (Sue); K. Tucker (Kathy); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); M.S. Goldberg (Mark); M. Tischkowitz (Marc); J. Simard (Jacques); P. Soucy (Penny); D. Eccles (Diana); N. Le (Nhu); A.-L. Borresen-Dale (Anne-Lise); V. Kristensen (Vessela); H.B. Salvesen (Helga); L. Bjorge (Line); E.V. Bandera (Elisa); H. Risch (Harvey); W. Zheng (Wei); A. Beeghly-Fadiel (Alicia); H. Cai (Hui); K. Pykäs (Katri); R.A.E.M. Tollenaar (Rob); A.M.W. van den Ouweland (Ans); I.L. Andrulis (Irene); J.A. Knight (Julia A.); S. Narod (Steven); P. Devilee (Peter); R. Winqvist (Robert); J.D. Figueroa (Jonine); M.H. Greene (Mark H.); P.L. Mai (Phuong); J.T. Loud (Jennifer); M. García-Closas (Montserrat); M. Schoemaker (Minouk); K. Czene (Kamila); H. Darabi (Hatef); I. McNeish (Iain); N. Siddiquil (Nadeem); R. Glasspool (Rosalind); A. Kwong (Ava); S.K. Park (Sue K.); S.-H. Teo (Soo-Hwang); S.-Y. Yoon (Sook-Yee); K. Matsuo (Keitaro); N. Hosono (Naoya); Y.L. Woo (Yin Ling); Y. Gao; L. Foretova (Lenka); C.F. Singer (Christian); C. Rappaport-Feurhauser (Christine); E. Friedman (Eitan); Y. Laitman (Yael); G. Rennert (Gad); E.N. Imyanitov (Evgeny); P.J. Hulick (Peter); O.I. Olopade (Olufunmilayo I.); L. Senter (Leigha); E. Olah (Edith); J.A. Doherty (Jennifer A.); J.M. Schildkraut (Joellen); L.B. Koppert (Lisa); L.A.L.M. Kiemeney (Bart); L.F. Massuger (Leon); L.S. Cook (Linda S.); T. Pejovic (Tanja); J. Li (Jingmei); Å. Borg (Åke); A. Öfverholm (Anna); M.A. Rossing (Mary Anne); N. Wentzensen (N.); K. Henriksson (Karin); A. Cox (Angela); S.S. Cross (Simon); B. Pasini (Barbara); M. Shah (Mitul); M. Kabisch (Maria); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); J. Gronwald (Jacek); B.A. Agnarsson (Bjarni); J. Kupryjanczyk (Jolanta); J. Moes-Sosnowska (Joanna); F. Fostira (Florentia); I. Konstantopoulou (I.); S. Slager (Susan); M. Jones (Michael); A.C. Antoniou (Antonis C.); A. Berchuck (Andrew); A.J. Swerdlow (Anthony ); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); P. Hall (Per); D.F. Easton (Douglas F.); F.J. Couch (Fergus); A.B. Spurdle (Amanda); D. Goldgar (David)

    2016-01-01

    textabstractBackground: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association.

  9. LHC Availability 2017: Technical Stop 1 to Technical Stop 2

    CERN Document Server

    Todd, Benjamin; Apollonio, Andrea; Walsh, David John; CERN. Geneva. ATS Department

    2017-01-01

    This document summarises the LHC machine availability for the period of Technical Stop 1 (TS1) to Technical Stop 2 (TS2) in 2017. This period was dedicated to proton physics with a bunch spacing of 25ns. This note has been produced and ratified by the Availability Working Group which has complied fault information for the period in question using the Accelerator Fault Tracker.

  10. Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

    Science.gov (United States)

    Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

    2018-01-25

    The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Development of a codon optimization strategy using the efor RED reporter gene as a test case

    Science.gov (United States)

    Yip, Chee-Hoo; Yarkoni, Orr; Ajioka, James; Wan, Kiew-Lian; Nathan, Sheila

    2018-04-01

    Synthetic biology is a platform that enables high-level synthesis of useful products such as pharmaceutically related drugs, bioplastics and green fuels from synthetic DNA constructs. Large-scale expression of these products can be achieved in an industrial compliant host such as Escherichia coli. To maximise the production of recombinant proteins in a heterologous host, the genes of interest are usually codon optimized based on the codon usage of the host. However, the bioinformatics freeware available for standard codon optimization might not be ideal in determining the best sequence for the synthesis of synthetic DNA. Synthesis of incorrect sequences can prove to be a costly error and to avoid this, a codon optimization strategy was developed based on the E. coli codon usage using the efor RED reporter gene as a test case. This strategy replaces codons encoding for serine, leucine, proline and threonine with the most frequently used codons in E. coli. Furthermore, codons encoding for valine and glycine are substituted with the second highly used codons in E. coli. Both the optimized and original efor RED genes were ligated to the pJS209 plasmid backbone using Gibson Assembly and the recombinant DNAs were transformed into E. coli E. cloni 10G strain. The fluorescence intensity per cell density of the optimized sequence was improved by 20% compared to the original sequence. Hence, the developed codon optimization strategy is proposed when designing an optimal sequence for heterologous protein production in E. coli.

  12. Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites

    Science.gov (United States)

    Sun, Yu; Tamarit, Daniel

    2017-01-01

    Abstract The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites. PMID:27540085

  13. Genome-wide analysis of codon usage bias in four sequenced cotton species.

    Science.gov (United States)

    Wang, Liyuan; Xing, Huixian; Yuan, Yanchao; Wang, Xianlin; Saeed, Muhammad; Tao, Jincai; Feng, Wei; Zhang, Guihua; Song, Xianliang; Sun, Xuezhen

    2018-01-01

    Codon usage bias (CUB) is an important evolutionary feature in a genome which provides important information for studying organism evolution, gene function and exogenous gene expression. The CUB and its shaping factors in the nuclear genomes of four sequenced cotton species, G. arboreum (A2), G. raimondii (D5), G. hirsutum (AD1) and G. barbadense (AD2) were analyzed in the present study. The effective number of codons (ENC) analysis showed the CUB was weak in these four species and the four subgenomes of the two tetraploids. Codon composition analysis revealed these four species preferred to use pyrimidine-rich codons more frequently than purine-rich codons. Correlation analysis indicated that the base content at the third position of codons affect the degree of codon preference. PR2-bias plot and ENC-plot analyses revealed that the CUB patterns in these genomes and subgenomes were influenced by combined effects of translational selection, directional mutation and other factors. The translational selection (P2) analysis results, together with the non-significant correlation between GC12 and GC3, further revealed that translational selection played the dominant role over mutation pressure in the codon usage bias. Through relative synonymous codon usage (RSCU) analysis, we detected 25 high frequency codons preferred to end with T or A, and 31 low frequency codons inclined to end with C or G in these four species and four subgenomes. Finally, 19 to 26 optimal codons with 19 common ones were determined for each species and subgenomes, which preferred to end with A or T. We concluded that the codon usage bias was weak and the translation selection was the main shaping factor in nuclear genes of these four cotton genomes and four subgenomes.

  14. Chloroplast DNA codon use: evidence for selection at the psb A locus based on tRNA availability.

    Science.gov (United States)

    Morton, B R

    1993-09-01

    Codon use in the three sequenced chloroplast genomes (Marchantia, Oryza, and Nicotiana) is examined. The chloroplast has a bias in that codons NNA and NNT are favored over synonymous NNC and NNG codons. This appears to be a consequence of an overall high A + T content of the genome. This pattern of codon use is not followed by the psb A gene of all three genomes and other psb A sequences examined. In this gene, the codon use favors NNC over NNT for twofold degenerate amino acids. In each case the only tRNA coded by the genome is complementary to the NNC codon. This codon use is similar to the codon use by chloroplast genes examined from Chlamydomonas reinhardtii. Since psb A is the major translation product of the chloroplast, this suggests that selection is acting on the codon use of this gene to adapt codons to tRNA availability, as previously suggested for unicellular organisms.

  15. Codon bias and gene ontology in holometabolous and hemimetabolous insects.

    Science.gov (United States)

    Carlini, David B; Makowski, Matthew

    2015-12-01

    The relationship between preferred codon use (PCU), developmental mode, and gene ontology (GO) was investigated in a sample of nine insect species with sequenced genomes. These species were selected to represent two distinct modes of insect development, holometabolism and hemimetabolism, with an aim toward determining whether the differences in developmental timing concomitant with developmental mode would be mirrored by differences in PCU in their developmental genes. We hypothesized that the developmental genes of holometabolous insects should be under greater selective pressure for efficient translation, manifest as increased PCU, than those of hemimetabolous insects because holometabolism requires abundant protein expression over shorter time intervals than hemimetabolism, where proteins are required more uniformly in time. Preferred codon sets were defined for each species, from which the frequency of PCU for each gene was obtained. Although there were substantial differences in the genomic base composition of holometabolous and hemimetabolous insects, both groups exhibited a general preference for GC-ending codons, with the former group having higher PCU averaged across all genes. For each species, the biological process GO term for each gene was assigned that of its Drosophila homolog(s), and PCU was calculated for each GO term category. The top two GO term categories for PCU enrichment in the holometabolous insects were anatomical structure development and cell differentiation. The increased PCU in the developmental genes of holometabolous insects may reflect a general strategy to maximize the protein production of genes expressed in bursts over short time periods, e.g., heat shock proteins. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 686-698, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  16. Essentiality, conservation, evolutionary pressure and codon bias in bacterial genomes.

    Science.gov (United States)

    Dilucca, Maddalena; Cimini, Giulio; Giansanti, Andrea

    2018-07-15

    Essential genes constitute the core of genes which cannot be mutated too much nor lost along the evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bacterial species, each one characterised by its own codon usage bias. Confirming previous results on E. coli, we show the existence of a universal exponential relation between gene essentiality and conservation in bacteria. Moreover, we show that, within each bacterial genome, there are at least two groups of functionally distinct genes, characterised by different levels of conservation and codon bias: i) a core of essential genes, mainly related to cellular information processing; ii) a set of less conserved nonessential genes with prevalent functions related to metabolism. In particular, the genes in the first group are more retained among species, are subject to a stronger purifying conservative selection and display a more limited repertoire of synonymous codons. The core of essential genes is close to the minimal bacterial genome, which is in the focus of recent studies in synthetic biology, though we confirm that orthologs of genes that are essential in one species are not necessarily essential in other species. We also list a set of highly shared genes which, reasonably, could constitute a reservoir of targets for new anti-microbial drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. IMPACTS OF BUS STOP IMPROVEMENTS

    Science.gov (United States)

    2018-03-23

    Improving bus stops by providing shelters, seating, signage, and sidewalks is relatively inexpensive and popular among riders and local officials. Making such improvements, however, is not often a priority for U.S. transit providers because of compet...

  18. A whistle-stop tour of statistics

    National Research Council Canada - National Science Library

    Everitt, Brian

    2012-01-01

    "Preface according to my Penguin English dictionary, whistle-stop, used before a noun means 'consisting of brief stops in several places' and this whistle-stop tour of statistics does just that, with...

  19. Sweet Spots and Door Stops

    Science.gov (United States)

    Thompson, Michael; Tsui, Stella; Leung, Chi Fan

    2011-01-01

    A sweet spot is referred to in sport as the perfect place to strike a ball with a racquet or bat. It is the point of contact between bat and ball where maximum results can be produced with minimal effort from the hand of the player. Similar physics can be applied to the less inspiring examples of door stops; the perfect position of a door stop is…

  20. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

    Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

  1. Probing Light Stops with Stoponium

    CERN Document Server

    Batell, Brian

    2015-01-01

    We derive new limits on light stops from diboson resonance searches in the $\\gamma\\gamma$, $Z \\gamma$, $ZZ$, $WW$ and $hh$ channels from the first run of the LHC. If the two-body decays of the light stop are mildly suppressed or kinematically forbidden, stoponium bound states will form in $pp$ collisions and subsequently decay via the pair annihilation of the constituent stops to diboson final states, yielding striking resonance signatures. Remarkably, we find that stoponium searches are highly complementary to direct collider searches and indirect probes of light stops such as Higgs coupling measurements. Using an empirical quarkonia potential model and including the first two $S$-wave stoponium states, we find that in the decoupling limit $m_{\\widetilde t_1} \\lesssim 130$ GeV is excluded for any value of the stop mixing angle and heavy stop mass by the combination of the latest resonance searches and the indirect constraints. The $\\gamma \\gamma$ searches are the most complementary to the indirect constraint...

  2. Second stop and sbottom searches with a stealth stop

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Hsin-Chia; Li, Lingfeng; Qin, Qin [Department of Physics, University of California,Davis, California 95616 (United States)

    2016-11-29

    The top squarks (stops) may be the most wanted particles after the Higgs boson discovery. The searches for the lightest stop have put strong constraints on its mass. However, there is still a search gap in the low mass region if the spectrum of the stop and the lightest neutralino is compressed. In that case, it may be easier to look for the second stop since naturalness requires both stops to be close to the weak scale. The current experimental searches for the second stop are based on the simplified model approach with the decay modes t̃{sub 2}→t̃{sub 1}Z and t̃{sub 2}→t̃{sub 1}h. However, in a realistic supersymmetric spectrum there is always a sbottom lighter than the second stop, hence the decay patterns are usually more complicated than the simplified model assumptions. In particular, there are often large branching ratios of the decays t̃{sub 2}→b̃{sub 1}W and b̃{sub 1}→t̃{sub 1}W as long as they are open. The decay chains can be even more complex if there are intermediate states of additional charginos and neutralinos in the decays. By studying several MSSM benchmark models at the 14 TeV LHC, we point out the importance of the multi-W final states in the second stop and the sbottom searches, such as the same-sign dilepton and multilepton signals, aside from the traditional search modes. The observed same-sign dilepton excesses at LHC Run 1 and Run 2 may be explained by some of our benchmark models. We also suggest that the vector boson tagging and a new kinematic variable may help to suppress the backgrounds and increase the signal significance for some search channels. Due to the complex decay patterns and lack of the dominant decay channels, the best reaches likely require a combination of various search channels at the LHC for the second stop and the lightest sbottom.

  3. Eukaryotic evolutionary transitions are associated with extreme codon bias in functionally-related proteins.

    Directory of Open Access Journals (Sweden)

    Nicholas J Hudson

    Full Text Available Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins--perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair--a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function--which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins--perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor--which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation.

  4. Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions.

    Science.gov (United States)

    Belinky, Frida; Rogozin, Igor B; Koonin, Eugene V

    2017-09-29

    Reconstruction of the evolution of start codons in 36 groups of closely related bacterial and archaeal genomes reveals purifying selection affecting AUG codons. The AUG starts are replaced by GUG and especially UUG significantly less frequently than expected under the neutral expectation derived from the frequencies of the respective nucleotide triplet substitutions in non-coding regions and in 4-fold degenerate sites. Thus, AUG is the optimal start codon that is actively maintained by purifying selection. However, purifying selection on start codons is significantly weaker than the selection on the same codons in coding sequences, although the switches between the codons result in conservative amino acid substitutions. The only exception is the AUG to UUG switch that is strongly selected against among start codons. Selection on start codons is most pronounced in evolutionarily conserved, highly expressed genes. Mutation of the start codon to a sub-optimal form (GUG or UUG) tends to be compensated by mutations in the Shine-Dalgarno sequence towards a stronger translation initiation signal. Together, all these findings indicate that in prokaryotes, translation start signals are subject to weak but significant selection for maximization of initiation rate and, consequently, protein production.

  5. Control of ribosome traffic by position-dependent choice of synonymous codons

    International Nuclear Information System (INIS)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

    Messenger RNA (mRNA) encodes a sequence of amino acids by using codons. For most amino acids, there are multiple synonymous codons that can encode the amino acid. The translation speed can vary from one codon to another, thus there is room for changing the ribosome speed while keeping the amino acid sequence and hence the resulting protein. Recently, it has been noticed that the choice of the synonymous codon, via the resulting distribution of slow- and fast-translated codons, affects not only on the average speed of one ribosome translating the mRNA but also might have an effect on nearby ribosomes by affecting the appearance of ‘traffic jams’ where multiple ribosomes collide and form queues. To test this ‘context effect’ further, we here investigate the effect of the sequence of synonymous codons on the ribosome traffic by using a ribosome traffic model with codon-dependent rates, estimated from experiments. We compare the ribosome traffic on wild-type (WT) sequences and sequences where the synonymous codons were swapped randomly. By simulating translation of 87 genes, we demonstrate that the WT sequences, especially those with a high bias in codon usage, tend to have the ability to reduce ribosome collisions, hence optimizing the cellular investment in the translation apparatus. The magnitude of such reduction of the translation time might have a significant impact on the cellular growth rate and thereby have importance for the survival of the species. (paper)

  6. Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2017-08-01

    Full Text Available Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5′- and 3′-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix.

  7. Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

    Science.gov (United States)

    Liu, Wei; Shin, Dongwon; Ng, Martin; Sanbonmatsu, Karissa Y; Tor, Yitzhak; Cooperman, Barry S

    2017-08-29

    Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix.

  8. Codon 219 polymorphism of PRNP in healthy caucasians and Creutzfeldt-Jakob disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Petraroli, R.; Pocchiari, M. [Instituto Superiore di Sanita, Rome (Italy)

    1996-04-01

    A number of point and insert mutations of the PrP gene (PRNP) have been linked to familial Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSS). Moreover, the methionine/valine homozygosity at the polymorphic codon 129 of PRNP may cause a predisposition to sporadic and iatrogenic CJD or may control the age at onset of familial cases carrying either the 144-bp insertion or codon 178, codon 198, and codon 210 pathogenic mutations in PRNP. In addition, the association of methionine or valine at codon 129 and the point mutation at codon 178 on the same allele seem to play an important role in determining either fatal familial insomnia or CJD. However, it is noteworthy that a relationship between codon 129 polymorphism and accelerated pathogenesis (early age at onset or shorter duration of the disease) has not been seen in familial CJD patients with codon 200 mutation or in GSS patients with codon 102 mutation, arguing that other, as yet unidentified, gene products or environmental factors, or both, may influence the clinical expression of these diseases. 17 refs.

  9. Features of Recent Codon Evolution: A Comparative Polymorphism-Fixation Study

    Directory of Open Access Journals (Sweden)

    Zhongming Zhao

    2010-01-01

    Full Text Available Features of amino-acid and codon changes can provide us important insights on protein evolution. So far, investigators have often examined mutation patterns at either interspecies fixed substitution or intraspecies nucleotide polymorphism level, but not both. Here, we performed a unique analysis of a combined set of intra-species polymorphisms and inter-species substitutions in human codons. Strong difference in mutational pattern was found at codon positions 1, 2, and 3 between the polymorphism and fixation data. Fixation had strong bias towards increasing the rarest codons but decreasing the most frequently used codons, suggesting that codon equilibrium has not been reached yet. We detected strong CpG effect on CG-containing codons and subsequent suppression by fixation. Finally, we detected the signature of purifying selection against A∣U dinucleotides at synonymous dicodon boundaries. Overall, fixation process could effectively and quickly correct the volatile changes introduced by polymorphisms so that codon changes could be gradual and directional and that codon composition could be kept relatively stable during evolution.

  10. Both structural and non-structural forms of the readthrough protein of cucurbit aphid-borne yellows virus are essential for efficient systemic infection of plants.

    Directory of Open Access Journals (Sweden)

    Sylvaine Boissinot

    Full Text Available Cucurbit aphid-borne yellows virus (CABYV is a polerovirus (Luteoviridae family with a capsid composed of the major coat protein and a minor component referred to as the readthrough protein (RT. Two forms of the RT were reported: a full-length protein of 74 kDa detected in infected plants and a truncated form of 55 kDa (RT* incorporated into virions. Both forms were detected in CABYV-infected plants. To clarify the specific roles of each protein in the viral cycle, we generated by deletion a polerovirus mutant able to synthesize only the RT* which is incorporated into the particle. This mutant was unable to move systemically from inoculated leaves inferring that the C-terminal half of the RT is required for efficient long-distance transport of CABYV. Among a collection of CABYV mutants bearing point mutations in the central domain of the RT, we obtained a mutant impaired in the correct processing of the RT which does not produce the RT*. This mutant accumulated very poorly in upper non-inoculated leaves, suggesting that the RT* has a functional role in long-distance movement of CABYV. Taken together, these results infer that both RT proteins are required for an efficient CABYV movement.

  11. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation.

    Science.gov (United States)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-12-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RTCter) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RTCter. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Both structural and non-structural forms of the readthrough protein of cucurbit aphid-borne yellows virus are essential for efficient systemic infection of plants.

    Science.gov (United States)

    Boissinot, Sylvaine; Erdinger, Monique; Monsion, Baptiste; Ziegler-Graff, Véronique; Brault, Véronique

    2014-01-01

    Cucurbit aphid-borne yellows virus (CABYV) is a polerovirus (Luteoviridae family) with a capsid composed of the major coat protein and a minor component referred to as the readthrough protein (RT). Two forms of the RT were reported: a full-length protein of 74 kDa detected in infected plants and a truncated form of 55 kDa (RT*) incorporated into virions. Both forms were detected in CABYV-infected plants. To clarify the specific roles of each protein in the viral cycle, we generated by deletion a polerovirus mutant able to synthesize only the RT* which is incorporated into the particle. This mutant was unable to move systemically from inoculated leaves inferring that the C-terminal half of the RT is required for efficient long-distance transport of CABYV. Among a collection of CABYV mutants bearing point mutations in the central domain of the RT, we obtained a mutant impaired in the correct processing of the RT which does not produce the RT*. This mutant accumulated very poorly in upper non-inoculated leaves, suggesting that the RT* has a functional role in long-distance movement of CABYV. Taken together, these results infer that both RT proteins are required for an efficient CABYV movement.

  13. Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Medori, R.; Tritschler, H.J. (Universita di Bologna (Italy))

    1993-10-01

    Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologic findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.

  14. Revelation of Influencing Factors in Overall Codon Usage Bias of Equine Influenza Viruses.

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

    Full Text Available Equine influenza viruses (EIVs of H3N8 subtype are culprits of severe acute respiratory infections in horses, and are still responsible for significant outbreaks worldwide. Adaptability of influenza viruses to a particular host is significantly influenced by their codon usage preference, due to an absolute dependence on the host cellular machinery for their replication. In the present study, we analyzed genome-wide codon usage patterns in 92 EIV strains, including both H3N8 and H7N7 subtypes by computing several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU analysis disclosed bias of preferred synonymous codons towards A/U-ended codons. The overall codon usage bias in EIVs was slightly lower, and mainly affected by the nucleotide compositional constraints as inferred from the RSCU and effective number of codon (ENc analysis. Our data suggested that codon usage pattern in EIVs is governed by the interplay of mutation pressure, natural selection from its hosts and undefined factors. The H7N7 subtype was found less fit to its host (horse in comparison to H3N8, by possessing higher codon bias, lower mutation pressure and much less adaptation to tRNA pool of equine cells. To the best of our knowledge, this is the first report describing the codon usage analysis of the complete genomes of EIVs. The outcome of our study is likely to enhance our understanding of factors involved in viral adaptation, evolution, and fitness towards their hosts.

  15. Stop. Write! Writing Grounded Theory

    Directory of Open Access Journals (Sweden)

    Barney G. Glaser, PhD, Hon. PhD

    2012-06-01

    Full Text Available The message in this book, the dictum in this book, is to stop and write when the Grounded Theory (GT methodology puts you in that ready position. Stop unending conceptualization, unending data coverage, and unending listening to others who would egg you on with additional data, ideas and/or requirements or simply wait too long. I will discuss these ideas in detail. My experience with PhD candidates is that for the few who write when ready, many do not and SHOULD. Simply put, many write-up, but many more should.

  16. Could stops lighten the top?

    International Nuclear Information System (INIS)

    Bilal, A.; Ellis, J.; Fogli, G.L.

    1990-01-01

    The analysis of the presently available electroweak data including radiative corrections in the standard model suggests that the top quark weighs more than the Z 0 . We examine whether squark loops in the minimal supersymmetric model, particularly those involving stops (partners of the top quark), could reduce substantially the preferred range of top quark masses. Given the present lower bounds on squark masses, we find that stop effects can reduce the central value of m t by at most a few GeV, although they do make a very heavy top quark increasingly unlikely. (orig.)

  17. Codon and amino-acid distribution in DNA

    International Nuclear Information System (INIS)

    Kim, J.K.; Yang, S.I.; Kwon, Y.H.; Lee, E.I.

    2005-01-01

    According to the Zipf's law, the distribution of rank-ordered frequency of words in the natural language can be modelled on the power law. In this paper, we examine the frequency distribution of 64 codons over the coding and non-coding regions of 88 DNA from EMBL and GenBank database, using exponential fitting. Also, we regard 20 amino-acids as vocabulary, perform the same frequency analysis to the same database and show that amino-acids can be used as biological meaningful words for Zipf's approach. Our analysis suggests that a natural language structure may exist not only in the coding region of DNA but in the non-coding one of DNA

  18. Protein evolution via amino acid and codon elimination

    DEFF Research Database (Denmark)

    Goltermann, Lise; Larsen, Marie Sofie Yoo; Banerjee, Rajat

    2010-01-01

    BACKGROUND: Global residue-specific amino acid mutagenesis can provide important biological insight and generate proteins with altered properties, but at the risk of protein misfolding. Further, targeted libraries are usually restricted to a handful of amino acids because there is an exponential...... correlation between the number of residues randomized and the size of the resulting ensemble. Using GFP as the model protein, we present a strategy, termed protein evolution via amino acid and codon elimination, through which simplified, native-like polypeptides encoded by a reduced genetic code were obtained...... simultaneously), while retaining varying levels of activity. Combination of these substitutions to generate a Phe-free variant of GFP abolished fluorescence. Combinatorial re-introduction of five Phe residues, based on the activities of the respective single amino acid replacements, was sufficient to restore GFP...

  19. Analysis of the synonymous codon usage bias in recently emerged enterovirus D68 strains.

    Science.gov (United States)

    Karniychuk, Uladzimir U

    2016-09-02

    Understanding the codon usage pattern of a pathogen and relationship between pathogen and host's codon usage patterns has fundamental and applied interests. Enterovirus D68 (EV-D68) is an emerging pathogen with a potentially high public health significance. In the present study, the synonymous codon usage bias of 27 recently emerged, and historical EV-D68 strains was analyzed. In contrast to previously studied enteroviruses (enterovirus 71 and poliovirus), EV-D68 and human host have a high discrepancy between favored codons. Analysis of viral synonymous codon usage bias metrics, viral nucleotide/dinucleotide compositional parameters, and viral protein properties showed that mutational pressure is more involved in shaping the synonymous codon usage bias of EV-D68 than translation selection. Computation of codon adaptation indices allowed to estimate expression potential of the EV-D68 genome in several commonly used laboratory animals. This approach requires experimental validation and may provide an auxiliary tool for the rational selection of laboratory animals to model emerging viral diseases. Enterovirus D68 genome compositional and codon usage data can be useful for further pathogenesis, animal model, and vaccine design studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

    NARCIS (Netherlands)

    Kampman, E.; Voskuil, D.W.; Kraats, A.A. van; Balder, H.F.; Muijen, G.N.P. van; Goldbohm, R.A.; Veer, P. van 't

    2000-01-01

    K-ras gene mutations (codons 12 and 13) were determined by PCR-based mutant allele-specific amplification (MASA) in tumour tissue of 185 colon cancer patients: 36% harboured mutations, of which 82% were located in codon 12. High intakes of animal protein, calcium and poultry were differently

  1. Nuclear stopping in transmission experiments

    International Nuclear Information System (INIS)

    Glazov, Lev G.; Sigmund, Peter

    2003-01-01

    Energy-loss spectra, mean and peak energy loss, and straggling due to elastic nuclear scattering have been studied theoretically as a function of target thickness and deflection angle of an initially monochromatic and well-collimated ion beam. The goal of this work has been to provide a generally valid scheme for nuclear-stopping corrections, allowing to determine electronic-stopping forces from energy-loss spectra measured in transmission geometry. Calculations have been based on the generalized Bothe-Landau theory of energy loss and multiple scattering. Our peak energy losses at zero emergence angle show close (∼10%) agreement with predictions of Fastrup et al. on the basis of the Bohr-Williams theory. However, predicted mean and peak energy losses are found to more sensitively depend on the underlying interatomic potential than unrestricted, i.e. angle-integrated mean or peak energy losses. Both elastic energy loss and multiple scattering are known to obey scaling laws involving only two combinations of the pertinent variables and atomic parameters. The dependence on deflection angle and foil thickness of mean and peak energy loss obeys a simple combination of these scaling laws. Comments are made on potential errors due to uncertainties in the nuclear-stopping correction applied in the literature with specific reference to central papers in low-velocity stopping

  2. Stop searches in flavourful supersymmetry

    CERN Document Server

    Crivellin, Andreas; Tunstall, Lewis C.

    2016-01-01

    Natural realisations of supersymmetry require light stops ${\\tilde t}_1$, making them a prime target of LHC searches for physics beyond the Standard Model. Depending on the kinematic region, the main search channels are ${\\tilde t_1}\\to t \\tilde \\chi^0_1$, ${\\tilde t_1}\\to W b \\tilde \\chi^0_1$ and ${\\tilde t_1}\\to c \\tilde \\chi^0_1$. We first examine the interplay of these decay modes with ${\\tilde c_1}\\to c \\tilde \\chi^0_1$ in a model-independent fashion, revealing the existence of large regions in parameter space which are excluded for any ${\\tilde t_1}\\to c \\tilde \\chi^0_1$ branching ratio. This effect is then illustrated for scenarios with stop-scharm mixing in the right-handed sector, where it has previously been observed that the stop mass limits can be significantly weakened for large mixing. Our analysis shows that once the LHC bounds from ${\\tilde c_1}\\to c \\tilde \\chi^0_1$ searches are taken into account, non-zero stop-scharm mixing leads only to a modest increase in the allowed regions of parameter...

  3. Correlated ion stopping in plasmas

    International Nuclear Information System (INIS)

    Zwicknagel, G.; Deutsch, C.

    1997-01-01

    The basic features of correlated ion stopping in plasmas are demonstrated by employing two opposite extremes of cluster structures, a statistical model with a spatial ion distribution of Gaussian shape and the highly regular configuration of N-ion chains and cubic boxes. In the case of the ion chains the resonant character of correlated stopping due to the interference of the excited wake fields is discussed in detail. The general behavior of correlation effects is summarized and its dependence on the ratio of cluster size and interion spacing to the screening length in the plasma, as well as the ratio of the cluster velocity to the mean electron velocity in the target, is stressed out. The validity and applicability of the dielectric response formalism used for describing correlated stopping is critically reviewed. A scheme is presented to extend the linear formalism to weak nonlinear situations that occur, in particular, for small highly charged clusters at moderate or low velocities. For the Gaussian cluster a fit formula is given, which allows a fast and accurate calculation of the enhancement of stopping due to correlation effects and applies for all degrees of degeneracy of the electrons and arbitrary cluster velocities. copyright 1997 The American Physical Society

  4. Remote Shutoff Stops Runaway Lawnmower

    Science.gov (United States)

    Grambo, Alan A.

    2007-01-01

    In this article, the author describes how electronics students at Central Nine Career Center designed a kill switch circuit to stop a runaway lawnmower. This project is ideal for a career center since the electronics/robotics, small engines and horticulture classes can all work together on their respective parts of the modification, installation…

  5. Reparametrizations with given stop data

    DEFF Research Database (Denmark)

    Raussen, Martin

    2009-01-01

    In [1] we performed a systematic investigation of reparametrizations of continuous paths in a Hausdorff space that relies crucially on a proper understanding of stop data of a (weakly increasing) reprametrizations of the unit interval. I am grateful to Marco Grandis (Genova) for pointing out to me...

  6. Reparametrizations with given stop data

    DEFF Research Database (Denmark)

    Raussen, Martin

    In [1], we performed a systematic investigation of reparametrizations of continuous paths in a Hausdorff space that relies crucially on a proper understanding of stop data of a (weakly increasing) reparametrization of the unit interval. I am indebted to Marco Grandis (Genova) for pointing out tome...

  7. Stopping Power for Degenerate Electrons

    Energy Technology Data Exchange (ETDEWEB)

    Singleton, Jr., Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-16

    This is a first attempt at calculating the BPS stopping power with electron degeneracy corrections. Section I establishes some notation and basic facts. Section II outlines the basics of the calculation, and in Section III contains some brief notes on how to proceed with the details of the calculation. The remaining work for the calculation starts with Section III.

  8. Plagiarism: Can It Be Stopped?

    Science.gov (United States)

    Christensen, G. Jay

    2011-01-01

    Plagiarism can be controlled, not stopped. The more appropriate question to ask is: What can be done to encourage students to "cheat" correctly by doing the assignment the way it was intended? Cheating by college students continues to reach epidemic proportions on selected campuses, as witnessed by the recent episode at Central Florida University,…

  9. Stop researching transformational leadership! Now!

    NARCIS (Netherlands)

    L.G. Tummers (Lars)

    2013-01-01

    markdownabstract__Intro__ Researchers all over the world, stop with your research on transformational leadership! Now! This could be the provocative conclusion after reading the recent article of Profs. Daan van Knippenberg and Sim Sitkin in The Academy of Management Annals (2013). These

  10. Stop researching transformational leadership! Now!

    OpenAIRE

    Tummers, Lars

    2013-01-01

    markdownabstract__Intro__ Researchers all over the world, stop with your research on transformational leadership! Now! This could be the provocative conclusion after reading the recent article of Profs. Daan van Knippenberg and Sim Sitkin in The Academy of Management Annals (2013). These leadership professors write about the problems surrounding transformational leadership.

  11. Persisting roughness when deposition stops.

    Science.gov (United States)

    Schwartz, Moshe; Edwards, S F

    2004-12-01

    Useful theories for growth of surfaces under random deposition of material have been developed by several authors. The simplest theory is that introduced by Edwards and Wilkinson (EW), which is linear and soluble. Its nonlinear generalization by Kardar, Parisi, and Zhang (KPZ) resulted in many subsequent studies. Yet both EW and KPZ theories contain an unphysical feature. When deposition of material is stopped, both theories predict that as time tends to infinity, the surface becomes flat. In fact, of course, the final surface is not flat, but simply has no gradients larger than the gradient related to the angle of repose. We modify the EW and KPZ theories to accommodate this feature and study the consequences for the simpler system which is a modification of the EW equation. In spite of the fact that the equation describing the evolution of the surface is not linear, we find that the steady state in the presence of noise is not very different in the long-wavelength limit from that of the linear EW equation. The situation is quite different from that of EW when deposition stops. Initially there is still some rearrangement of the surface, but that stops as everywhere on the surface the gradient is less than that related to the angle of repose. The most interesting feature observed after deposition stops is the emergence of history-dependent steady-state distributions.

  12. Tourette Syndrome: Help Stop Bullying

    Science.gov (United States)

    ... work on Tourette Syndrome Tourette Association information on bullying What it’s like to have Tourette – Mary tells her story What children wish people knew about Tourette Syndrome CDC Children’s Mental Health StopBullying.gov Features Media Sign up for Features ...

  13. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Chapuis, Sophie [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Revers, Frédéric [INRA, Université de Bordeaux, UMR 1332 de Biologie du Fruit et Pathologie, 33882 Villenave d’Ornon (France); Ziegler-Graff, Véronique [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Brault, Véronique, E-mail: veronique.brault@colmar.inra.fr [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France)

    2015-12-15

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT{sub Cter}) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT{sub Cter}. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT{sub Cter} in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  14. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    International Nuclear Information System (INIS)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-01-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT_C_t_e_r) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT_C_t_e_r. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT_C_t_e_r in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  15. Progress in understanding heavy-ion stopping

    Energy Technology Data Exchange (ETDEWEB)

    Sigmund, P., E-mail: sigmund@sdu.dk [Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, DK-5230 Odense M (Denmark); Schinner, A. [Institut für Experimentalphysik, Johannes Kepler Universität, A-4040 Linz (Austria)

    2016-09-01

    We report some highlights of our work with heavy-ion stopping in the energy range where Bethe stopping theory breaks down. Main tools are our binary stopping theory (PASS code), the reciprocity principle, and Paul’s data base. Comparisons are made between PASS and three alternative theoretical schemes (CasP, HISTOP and SLPA). In addition to equilibrium stopping we discuss frozen-charge stopping, deviations from linear velocity dependence below the Bragg peak, application of the reciprocity principle in low-velocity stopping, modeling of equilibrium charges, and the significance of the so-called effective charge.

  16. Progress in understanding heavy-ion stopping

    International Nuclear Information System (INIS)

    Sigmund, P.; Schinner, A.

    2016-01-01

    We report some highlights of our work with heavy-ion stopping in the energy range where Bethe stopping theory breaks down. Main tools are our binary stopping theory (PASS code), the reciprocity principle, and Paul’s data base. Comparisons are made between PASS and three alternative theoretical schemes (CasP, HISTOP and SLPA). In addition to equilibrium stopping we discuss frozen-charge stopping, deviations from linear velocity dependence below the Bragg peak, application of the reciprocity principle in low-velocity stopping, modeling of equilibrium charges, and the significance of the so-called effective charge.

  17. Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells.

    Science.gov (United States)

    Zhao, Fangzhou; Yu, Chien-Hung; Liu, Yi

    2017-08-21

    Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation. In addition, codon usage regulates ribosome movement and stalling on mRNA during translation. Finally, we show that codon usage affects protein structure and function in vitro and in Drosophila cells. Together, these results suggest that the effect of codon usage on translation elongation speed is a conserved mechanism from fungi to animals that can affect protein folding in eukaryotic organisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. A single sequence context cannot satisfy all non-AUG initiator codons in yeast†

    Directory of Open Access Journals (Sweden)

    Wang Tzu-Ling

    2010-07-01

    Full Text Available Abstract Background Previous studies in Saccharomyces cerevisiae showed that ALA1 (encoding alanyl-tRNA synthetase and GRS1 (encoding glycyl-tRNA synthetase respectively use ACG and TTG as their alternative translation initiator codons. To explore if any other non-ATG triplets can act as initiator codons in yeast, ALA1 was used as a reporter for screening. Results We show herein that except for AAG and AGG, all triplets that differ from ATG by a single nucleotide were able to serve as initiator codons in ALA1. Among these initiator codons, TTG, CTG, ACG, and ATT had ~50% initiating activities relative to that of ATG, while GTG, ATA, and ATC had ~20% initiating activities relative to that of ATG. Unexpectedly, these non-AUG initiator codons exhibited different preferences toward various sequence contexts. In particular, GTG was one of the most efficient non-ATG initiator codons, while ATA was essentially inactive in the context of GRS1. Conclusion This finding indicates that a sequence context that is favorable for a given non-ATG initiator codon might not be as favorable for another.

  19. Genome-Wide Analysis of the Synonymous Codon Usage Patterns in Riemerella anatipestifer

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    2016-08-01

    Full Text Available Riemerella anatipestifer (RA belongs to the Flavobacteriaceae family and can cause a septicemia disease in poultry. The synonymous codon usage patterns of bacteria reflect a series of evolutionary changes that enable bacteria to improve tolerance of the various environments. We detailed the codon usage patterns of RA isolates from the available 12 sequenced genomes by multiple codon and statistical analysis. Nucleotide compositions and relative synonymous codon usage (RSCU analysis revealed that A or U ending codons are predominant in RA. Neutrality analysis found no significant correlation between GC12 and GC3 (p > 0.05. Correspondence analysis and ENc-plot results showed that natural selection dominated over mutation in the codon usage bias. The tree of cluster analysis based on RSCU was concordant with dendrogram based on genomic BLAST by neighbor-joining method. By comparative analysis, about 50 highly expressed genes that were orthologs across all 12 strains were found in the top 5% of high CAI value. Based on these CAI values, we infer that RA contains a number of predicted highly expressed coding sequences, involved in transcriptional regulation and metabolism, reflecting their requirement for dealing with diverse environmental conditions. These results provide some useful information on the mechanisms that contribute to codon usage bias and evolution of RA.

  20. Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

    Science.gov (United States)

    Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

    2018-02-01

    The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

  1. Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

    Directory of Open Access Journals (Sweden)

    Tarikul Huda Mazumder

    Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

  2. Codon 201Gly Polymorphic Type of the DCC Gene is Related to Disseminated Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Xiao-Tang Kong

    2001-01-01

    Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

  3. ChloroMitoCU: Codon patterns across organelle genomes for functional genomics and evolutionary applications.

    Science.gov (United States)

    Sablok, Gaurav; Chen, Ting-Wen; Lee, Chi-Ching; Yang, Chi; Gan, Ruei-Chi; Wegrzyn, Jill L; Porta, Nicola L; Nayak, Kinshuk C; Huang, Po-Jung; Varotto, Claudio; Tang, Petrus

    2017-06-01

    Organelle genomes are widely thought to have arisen from reduction events involving cyanobacterial and archaeal genomes, in the case of chloroplasts, or α-proteobacterial genomes, in the case of mitochondria. Heterogeneity in base composition and codon preference has long been the subject of investigation of topics ranging from phylogenetic distortion to the design of overexpression cassettes for transgenic expression. From the overexpression point of view, it is critical to systematically analyze the codon usage patterns of the organelle genomes. In light of the importance of codon usage patterns in the development of hyper-expression organelle transgenics, we present ChloroMitoCU, the first-ever curated, web-based reference catalog of the codon usage patterns in organelle genomes. ChloroMitoCU contains the pre-compiled codon usage patterns of 328 chloroplast genomes (29,960 CDS) and 3,502 mitochondrial genomes (49,066 CDS), enabling genome-wide exploration and comparative analysis of codon usage patterns across species. ChloroMitoCU allows the phylogenetic comparison of codon usage patterns across organelle genomes, the prediction of codon usage patterns based on user-submitted transcripts or assembled organelle genes, and comparative analysis with the pre-compiled patterns across species of interest. ChloroMitoCU can increase our understanding of the biased patterns of codon usage in organelle genomes across multiple clades. ChloroMitoCU can be accessed at: http://chloromitocu.cgu.edu.tw/. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  4. Codon usage is associated with the evolutionary age of genes in metazoan genomes

    Directory of Open Access Journals (Sweden)

    Linial Nathan

    2009-12-01

    Full Text Available Abstract Background Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes. Results We assign an evolutionary age to a gene based on the relative positions of its identified homologues in a standard phylogenetic tree. This yields a classification of all genes in a genome to several evolutionary age classes. The present study starts from the observation that each age class of genes has a unique codon usage and proceeds to provide a quantitative analysis of the codon usage in these classes. This observation is made for the genomes of Homo sapiens, Mus musculus, and Drosophila melanogaster. It is even more remarkable that the differences between codon usages in different age groups exhibit similar and consistent behavior in various organisms. While we find that GC content and gene length are also associated with the evolutionary age of genes, they can provide only a partial explanation for the observed codon usage. Conclusion While factors such as GC content, mutational bias, and selection shape the codon usage in a genome, the evolutionary history of an organism over hundreds of millions of years is an overlooked property that is strongly linked to GC content, protein length, and, even more significantly, to the codon usage of metazoan genomes.

  5. A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes.

    Science.gov (United States)

    Mühlhausen, Stefanie; Findeisen, Peggy; Plessmann, Uwe; Urlaub, Henning; Kollmar, Martin

    2016-07-01

    The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. © 2016 Mühlhausen et al.; Published by Cold Spring Harbor Laboratory Press.

  6. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... your fingers and from your nails to your face and mouth. To help you stop biting your ... re inclined to bite may help solve the problem. Try to gradually stop biting your nails: Some ...

  7. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources ... Try to gradually stop biting your nails: Some doctors recommend taking a gradual approach to break the habit. Try to stop biting ...

  8. Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution.

    Science.gov (United States)

    Nasrullah, Izza; Butt, Azeem M; Tahir, Shifa; Idrees, Muhammad; Tong, Yigang

    2015-08-26

    The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV.

  9. Why does sleep stop migraine?

    Science.gov (United States)

    Bigal, Marcelo E; Hargreaves, Richard J

    2013-10-01

    The relationship between sleep and migraine headaches is complex. Changes in sleep patterns can trigger migraine attacks, and sleep disorders may be associated with increased migraine frequency. Furthermore, migraine patients and their doctors very consistently report that sleep relieves already established migraine attacks. Herein we will try to answer the question, "Why does sleep stop migraine?" Since evidence for this relationship is largely based on empirical clinical observation, we will not provide a clinical review of the association. Instead, we will focus on the pathophysiology of migraine attacks and its intersections with sleep biology.

  10. Codon usage bias and phylogenetic analysis of mitochondrial ND1 gene in pisces, aves, and mammals.

    Science.gov (United States)

    Uddin, Arif; Choudhury, Monisha Nath; Chakraborty, Supriyo

    2018-01-01

    The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters. The codon usage bias of MT-ND1 was low but the expression level was high as revealed from high ENC and CAI value. Correspondence analysis (COA) suggests that the pattern of codon usage for MT-ND1 gene is not same across species and that compositional constraint played an important role in codon usage pattern of this gene among pisces, aves, and mammals. From the regression equation of GC12 on GC3, it can be inferred that the natural selection might have played a dominant role while mutation pressure played a minor role in influencing the codon usage patterns. Further, ND1 gene has a discrepancy with cytochrome B (CYB) gene in preference of codons as evident from COA. The codon usage bias was low. It is influenced by nucleotide composition, natural selection, mutation pressure, length (number) of amino acids, and relative dinucleotide composition. This study helps in understanding the molecular biology, genetics, evolution of MT-ND1 gene, and also for designing a synthetic gene.

  11. Codon usage and expression level of human mitochondrial 13 protein coding genes across six continents.

    Science.gov (United States)

    Chakraborty, Supriyo; Uddin, Arif; Mazumder, Tarikul Huda; Choudhury, Monisha Nath; Malakar, Arup Kumar; Paul, Prosenjit; Halder, Binata; Deka, Himangshu; Mazumder, Gulshana Akthar; Barbhuiya, Riazul Ahmed; Barbhuiya, Masuk Ahmed; Devi, Warepam Jesmi

    2017-12-02

    The study of codon usage coupled with phylogenetic analysis is an important tool to understand the genetic and evolutionary relationship of a gene. The 13 protein coding genes of human mitochondria are involved in electron transport chain for the generation of energy currency (ATP). However, no work has yet been reported on the codon usage of the mitochondrial protein coding genes across six continents. To understand the patterns of codon usage in mitochondrial genes across six different continents, we used bioinformatic analyses to analyze the protein coding genes. The codon usage bias was low as revealed from high ENC value. Correlation between codon usage and GC3 suggested that all the codons ending with G/C were positively correlated with GC3 but vice versa for A/T ending codons with the exception of ND4L and ND5 genes. Neutrality plot revealed that for the genes ATP6, COI, COIII, CYB, ND4 and ND4L, natural selection might have played a major role while mutation pressure might have played a dominant role in the codon usage bias of ATP8, COII, ND1, ND2, ND3, ND5 and ND6 genes. Phylogenetic analysis indicated that evolutionary relationships in each of 13 protein coding genes of human mitochondria were different across six continents and further suggested that geographical distance was an important factor for the origin and evolution of 13 protein coding genes of human mitochondria. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  12. Identification of the translational start site of codon-optimized mCherry in Mycobacterium tuberculosis

    OpenAIRE

    Carroll, Paul; Muwanguzi-Karugaba, Julian; Melief, Eduard; Files, Megan; Parish, Tanya

    2014-01-01

    Background Fluorescent proteins are used widely as reporter genes in many organisms. We previously codon-optimized mCherry for Mycobacterium tuberculosis and generated expression constructs with high level expression in mycobacteria with multiple uses in vitro and in vivo. However, little is known about the expression of fluorescent proteins in mycobacteria and the translational start codon for mCherry has not been experimentally determined. Results We determined the translational start site ...

  13. Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jerusa Smid

    2013-07-01

    Full Text Available Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD. Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM, 42.2% methionine valine (MV, 12.1% valine (VV; and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05. There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.

  14. Optimal Stopping with Information Constraint

    International Nuclear Information System (INIS)

    Lempa, Jukka

    2012-01-01

    We study the optimal stopping problem proposed by Dupuis and Wang (Adv. Appl. Probab. 34:141–157, 2002). In this maximization problem of the expected present value of the exercise payoff, the underlying dynamics follow a linear diffusion. The decision maker is not allowed to stop at any time she chooses but rather on the jump times of an independent Poisson process. Dupuis and Wang (Adv. Appl. Probab. 34:141–157, 2002), solve this problem in the case where the underlying is a geometric Brownian motion and the payoff function is of American call option type. In the current study, we propose a mild set of conditions (covering the setup of Dupuis and Wang in Adv. Appl. Probab. 34:141–157, 2002) on both the underlying and the payoff and build and use a Markovian apparatus based on the Bellman principle of optimality to solve the problem under these conditions. We also discuss the interpretation of this model as optimal timing of an irreversible investment decision under an exogenous information constraint.

  15. Absolute in vivo translation rates of individual codons in Escherichia coli: The two glutamic acid codons GAA and GAG are translated with a threefold difference in rate

    DEFF Research Database (Denmark)

    Sørensen, M.A.; Pedersen, Steen

    1991-01-01

    We have determined the absolute translation rates for four individual codons in Escherichia coli. We used our previously described system for direct measurements of in vivo translation rates using small, in-frame inserts in the lacZ gene. The inserts consisted of multiple synthetic 30 base-pair D...

  16. Codon usage bias: causative factors, quantification methods and genome-wide patterns: with emphasis on insect genomes.

    Science.gov (United States)

    Behura, Susanta K; Severson, David W

    2013-02-01

    Codon usage bias refers to the phenomenon where specific codons are used more often than other synonymous codons during translation of genes, the extent of which varies within and among species. Molecular evolutionary investigations suggest that codon bias is manifested as a result of balance between mutational and translational selection of such genes and that this phenomenon is widespread across species and may contribute to genome evolution in a significant manner. With the advent of whole-genome sequencing of numerous species, both prokaryotes and eukaryotes, genome-wide patterns of codon bias are emerging in different organisms. Various factors such as expression level, GC content, recombination rates, RNA stability, codon position, gene length and others (including environmental stress and population size) can influence codon usage bias within and among species. Moreover, there has been a continuous quest towards developing new concepts and tools to measure the extent of codon usage bias of genes. In this review, we outline the fundamental concepts of evolution of the genetic code, discuss various factors that may influence biased usage of synonymous codons and then outline different principles and methods of measurement of codon usage bias. Finally, we discuss selected studies performed using whole-genome sequences of different insect species to show how codon bias patterns vary within and among genomes. We conclude with generalized remarks on specific emerging aspects of codon bias studies and highlight the recent explosion of genome-sequencing efforts on arthropods (such as twelve Drosophila species, species of ants, honeybee, Nasonia and Anopheles mosquitoes as well as the recent launch of a genome-sequencing project involving 5000 insects and other arthropods) that may help us to understand better the evolution of codon bias and its biological significance. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

  17. Optimally stopped variational quantum algorithms

    Science.gov (United States)

    Vinci, Walter; Shabani, Alireza

    2018-04-01

    Quantum processors promise a paradigm shift in high-performance computing which needs to be assessed by accurate benchmarking measures. In this article, we introduce a benchmark for the variational quantum algorithm (VQA), recently proposed as a heuristic algorithm for small-scale quantum processors. In VQA, a classical optimization algorithm guides the processor's quantum dynamics to yield the best solution for a given problem. A complete assessment of the scalability and competitiveness of VQA should take into account both the quality and the time of dynamics optimization. The method of optimal stopping, employed here, provides such an assessment by explicitly including time as a cost factor. Here, we showcase this measure for benchmarking VQA as a solver for some quadratic unconstrained binary optimization. Moreover, we show that a better choice for the cost function of the classical routine can significantly improve the performance of the VQA algorithm and even improve its scaling properties.

  18. How to stop global warming

    International Nuclear Information System (INIS)

    Goldenberg, J.

    1990-01-01

    This paper reports on how to stop global warming. At the Toronto Conference on Climate Change in 1988, the world's industrialized nations agreed on a goal of cutting greenhouse gas emissions 20 percent by the year 2005. This would not stabilize atmospheric levels of greenhouse gases but would at least slow their accumulation. Although difficult to achieve, the Toronto goal is certainly reachable. Newer, more efficient technologies can lower energy consumption without effecting economic output. CFC- substitutes can provide refrigeration. In fact, an international carbon tax of just $1 per barrel of oil, or $6 per ton of coal, would generate more than enough revenue to pay for the necessary fuel-saving measures. This tax could result from an international agreement similar to the 1987 Montreal Protocol, which obliges its signatories to cut down on production of CFCs

  19. Triplet-Based Codon Organization Optimizes the Impact of Synonymous Mutation on Nucleic Acid Molecular Dynamics.

    Science.gov (United States)

    Babbitt, Gregory A; Coppola, Erin E; Mortensen, Jamie S; Ekeren, Patrick X; Viola, Cosmo; Goldblatt, Dallan; Hudson, André O

    2018-02-01

    Since the elucidation of the genetic code almost 50 years ago, many nonrandom aspects of its codon organization remain only partly resolved. Here, we investigate the recent hypothesis of 'dual-use' codons which proposes that in addition to allowing adjustment of codon optimization to tRNA abundance, the degeneracy in the triplet-based genetic code also multiplexes information regarding DNA's helical shape and protein-binding dynamics while avoiding interference with other protein-level characteristics determined by amino acid properties. How such structural optimization of the code within eukaryotic chromatin could have arisen from an RNA world is a mystery, but would imply some preadaptation in an RNA context. We analyzed synonymous (protein-silent) and nonsynonymous (protein-altering) mutational impacts on molecular dynamics in 13823 identically degenerate alternative codon reorganizations, defined by codon transitions in 7680 GPU-accelerated molecular dynamic simulations of implicitly and explicitly solvated double-stranded aRNA and bDNA structures. When compared to all possible alternative codon assignments, the standard genetic code minimized the impact of synonymous mutations on the random atomic fluctuations and correlations of carbon backbone vector trajectories while facilitating the specific movements that contribute to DNA polymer flexibility. This trend was notably stronger in the context of RNA supporting the idea that dual-use codon optimization and informational multiplexing in DNA resulted from the preadaptation of the RNA duplex to resist changes to thermostability. The nonrandom and divergent molecular dynamics of synonymous mutations also imply that the triplet-based code may have resulted from adaptive functional expansion enabling a primordial doublet code to multiplex gene regulatory information via the shape and charge of the minor groove.

  20. Mapping the Plasticity of the E. coli Genetic Code with Orthogonal Pair Directed Sense Codon Reassignment.

    Science.gov (United States)

    Schmitt, Margaret A; Biddle, Wil; Fisk, John Domenic

    2018-04-18

    The relative quantitative importance of the factors that determine the fidelity of translation is largely unknown, which makes predicting the extent to which the degeneracy of the genetic code can be broken challenging. Our strategy of using orthogonal tRNA/aminoacyl tRNA synthetase pairs to precisely direct the incorporation of a single amino acid in response to individual sense and nonsense codons provides a suite of related data with which to examine the plasticity of the code. Each directed sense codon reassignment measurement is an in vivo competition experiment between the introduced orthogonal translation machinery and the natural machinery in E. coli. This report discusses 20 new, related genetic codes, in which a targeted E. coli wobble codon is reassigned to tyrosine utilizing the orthogonal tyrosine tRNA/aminoacyl tRNA synthetase pair from Methanocaldococcus jannaschii. One at a time, reassignment of each targeted sense codon to tyrosine is quantified in cells by measuring the fluorescence of GFP variants in which the essential tyrosine residue is encoded by a non-tyrosine codon. Significantly, every wobble codon analyzed may be partially reassigned with efficiencies ranging from 0.8% to 41%. The accumulation of the suite of data enables a qualitative dissection of the relative importance of the factors affecting the fidelity of translation. While some correlation was observed between sense codon reassignment and either competing endogenous tRNA abundance or changes in aminoacylation efficiency of the altered orthogonal system, no single factor appears to predominately drive translational fidelity. Evaluation of relative cellular fitness in each of the 20 quantitatively-characterized proteome-wide tyrosine substitution systems suggests that at a systems level, E. coli is robust to missense mutations.

  1. Stop Negative Thinking Effects for Drug Dependence

    OpenAIRE

    Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar

    2013-01-01

    The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...

  2. Are Stopped Strings Preferred in Sad Music?

    OpenAIRE

    David Huron; Caitlyn Trevor

    2017-01-01

    String instruments may be played either with open strings (where the string vibrates between the bridge and a hard wooden nut) or with stopped strings (where the string vibrates between the bridge and a performer's finger pressed against the fingerboard). Compared with open strings, stopped strings permit the use of vibrato and exhibit a darker timbre. Inspired by research on the timbre of sad speech, we test whether there is a tendency to use stopped strings in nominally sad music. Specifica...

  3. Measurement of stopping power of heavy ions

    International Nuclear Information System (INIS)

    Kitahara, Tetsuo

    1981-01-01

    The stopping power of heavy ions is discussed. In the low energy region, heavy ions keep some of their orbital electrons, and have equilibrium electron charge. The stopping power of penetrating particles depends on this effective charge. At present, it is hard to estimate this effective charge theoretically, accordingly, the estimation is made experimentally. Another difficulty in this estimation is that the Born approximation is not effective for heavy ions. In the low energy region, electronic stopping and nuclear stopping contribute to the stopping power. For the electronic stopping, a formula for the stopping power was given by Lindhard et al. The experimental values were obtained at GSI, and are inconsistent with the estimation by the Lindhard's formula. In the high energy region, where the Born approximation can be used, the Bethe's formula is applied, but the experimental data are scarce. Oscillations are seen in the Z dependence graph of the experimental stopping cross sections. Experimental works on the stopping power have been done. The differential and the integral methods were carried out. (Kato, T.)

  4. Slow, stopped and stored light

    International Nuclear Information System (INIS)

    Welch, G.; Scully, M.

    2005-01-01

    Light that can been slowed to walking pace could have applications in telecommunications, optical storage and quantum computing. Whether we use it to estimate how far away a thunderstorm is, or simply take it for granted that we can have a conversation with someone on the other side of the world, we all know that light travels extremely fast. Indeed, special relativity teaches us that nothing in the universe can ever move faster than the speed of light in a vacuum: 299 792 458 ms sup - sup 1. However, there is no such limitation on how slowly light can travel. For the last few years, researchers have been routinely slowing light to just a few metres per second, and have recently even stopped it dead in its tracks so that it can be stored for future use. Slow-light has considerable popular appeal, deriving perhaps from the importance of the speed of light in relativity and cosmology. If everyday objects such as cars or people can travel faster than 'slow' light, for example, then it might appear that relativistic effects could be observed at very low speeds. Although this is not the case, slow light nonetheless promises to play an important role in optical technology because it allows light to be delayed for any period of time desired. This could lead to all-optical routers that would increase the bandwidth of the Internet, and applications in optical data storage, quantum information and even radar. (U.K.)

  5. Stopping atoms with diode lasers

    International Nuclear Information System (INIS)

    Watts, R.N.; Wieman, C.E.

    1986-01-01

    The use of light pressure to cool and stop neutral atoms has been an area of considerable interest recently. Cooled neutral atoms are needed for a variety of interesting experiments involving neutral atom traps and ultrahigh-resolution spectroscopy. Laser cooling of sodium has previously been demonstrated using elegant but quite elaborate apparatus. These techniques employed stabilized dye lasers and a variety of additional sophisticated hardware. The authors have demonstrated that a frequency chirp technique can be implemented using inexpensive diode lasers and simple electronics. In this technique the atoms in an atomic beam scatter resonant photons from a counterpropagating laser beam. The momentum transfer from the photons slows the atoms. The primary difficulty is that as the atoms slow their Doppler shift changes, and so they are no longer in resonance with the incident photons. In the frequency chirp technique this is solved by rapidly changing the laser frequency so that the atoms remain in resonance. To achieve the necessary frequency sweep with a dye laser one must use an extremely sophisticated high-speed electrooptic modulator. With a diode laser, however, the frequency can be smoothly and rapidly varied over many gigahertz simply by changing the injection current

  6. Electron and Positron Stopping Powers of Materials

    Science.gov (United States)

    SRD 7 NIST Electron and Positron Stopping Powers of Materials (PC database for purchase)   The EPSTAR database provides rapid calculations of stopping powers (collisional, radiative, and total), CSDA ranges, radiation yields and density effect corrections for incident electrons or positrons with kinetic energies from 1 keV to 10 GeV, and for any chemically defined target material.

  7. Addressing production stops in the food industry

    DEFF Research Database (Denmark)

    Hansen, Zaza Nadja Lee; Herbert, Luke Thomas; Jacobsen, Peter

    2014-01-01

    This paper investigates the challenges in the food industry which causes the production lines to stop, illustrated by a case study of an SME size company in the baked goods sector in Denmark. The paper proposes key elements this sector needs to be aware of to effectively address production stops......, and gives examples of the unique challenges faced by the SME food industry....

  8. Perceptual assessment of fricative--stop coarticulation.

    Science.gov (United States)

    Repp, B H; Mann, V A

    1981-04-01

    The perceptual dependence of stop consonants on preceding fricatives [Mann and Repp, J. Acoust. Soc. Am. 69, 548--558 (1981)] was further investigated in two experiments employing both natural and synthetic speech. These experiments consistently replicated our original finding that listeners, report velar stops following [s]. In addition, our data confirmed earlier reports that natural fricative noises (excerpted from utterances of [st alpha], [sk alpha], [(formula: see text)k alpha]) contain cues to the following stop consonants; this was revealed in subjects' identifications of stops from isolated fricative noises and from stimuli consisting of these noises followed by synthetic CV portions drawn from a [t alpha]--[k alpha] continuum. However, these cues in the noise portion could not account for the contextual effect of fricative identity ([formula: see text] versus [sp) on stop perception (more "k" responses following [s]). Rather, this effect seems to be related to a coarticulatory influence of a preceding fricative on stop production; Subjects' responses to excised natural CV portions (with bursts and aspiration removed) were biased towards a relatively more forward place of stop articulation when the CVs had originally been preceded by [s]; and the identification of a preceding ambiguous fricative was biased in the direction of the original fricative context in which a given CV portion had been produced. These findings support an articulatory explanation for the effect of preceding fricatives on stop consonant perception.

  9. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... of hangnails, or other triggers, such as boredom, stress, or anxiety. By figuring out what causes you to bite your nails, you can figure out how to avoid these situations and develop a plan to stop. Just knowing when you’re inclined to bite may help solve the problem. Try to gradually stop biting ...

  10. All in One Stop? The Accessibility of Work Support Programs at One-Stop Centers.

    Science.gov (United States)

    Richer, Elise; Kubo, Hitomi; Frank, Abbey

    The accessibility of work support programs at one-stop centers was examined in a study during which 33 telephone directors or managers of one-stop centers in 22 states were interviewed by telephone. The interviews established the existence of extensive differences between one-stop centers from the standpoint of all aspects of their operation,…

  11. Rare codons effect on expression of recombinant gene cassette in Escherichia coli BL21(DE3

    Directory of Open Access Journals (Sweden)

    Aghil Esmaeili-Bandboni

    2017-11-01

    Full Text Available Objective: To demonstrate the sensitivity of expression of fusion genes to existence of a large number of rare codons in recombinant gene sequenced. Methods: Primers for amplification of cholera toxin B, Shiga toxin B and gfp genes were designed by Primer3 software and synthesized. All of these 3 genes were cloned. Then the genes were fused together by restriction sites and enzymatic method. Two linkers were used as a flexible bridge in connection of these genes. Results: Cloning and fusion of cholera toxin B, Shiga toxin B and gfp genes were done correctly. After that, expression of the recombinant gene construction was surveyed. Conclusions: According to what was seen, because of the accumulation of 12 rare codons of Shiga toxin B and 19 rare codons of cholera toxin B in this gene cassette, the expression of the recombinant gene cassette, in Escherichia coli BL21, failed.

  12. ANT: Software for Generating and Evaluating Degenerate Codons for Natural and Expanded Genetic Codes.

    Science.gov (United States)

    Engqvist, Martin K M; Nielsen, Jens

    2015-08-21

    The Ambiguous Nucleotide Tool (ANT) is a desktop application that generates and evaluates degenerate codons. Degenerate codons are used to represent DNA positions that have multiple possible nucleotide alternatives. This is useful for protein engineering and directed evolution, where primers specified with degenerate codons are used as a basis for generating libraries of protein sequences. ANT is intuitive and can be used in a graphical user interface or by interacting with the code through a defined application programming interface. ANT comes with full support for nonstandard, user-defined, or expanded genetic codes (translation tables), which is important because synthetic biology is being applied to an ever widening range of natural and engineered organisms. The Python source code for ANT is freely distributed so that it may be used without restriction, modified, and incorporated in other software or custom data pipelines.

  13. Stopping of hypervelocity clusters in solids

    International Nuclear Information System (INIS)

    Anders, Christian; Ziegenhain, Gerolf; Urbassek, Herbert M; Bringa, Eduardo M

    2011-01-01

    Using molecular-dynamics simulations, we study the processes underlying the stopping of energetic clusters upon impact in matter. We investigate self-bombardment of both a metallic (Cu) and a van-der-Waals bonded (frozen Ar) target. Clusters with sizes up to N = 10 4 atoms and with energies per atom of E/N = 0.1-1600 eV atom -1 were studied. We find that the stopping force exerted on a cluster follows an N 2/3 -dependence with cluster size N; thus large clusters experience less stopping than equi-velocity atoms. In the course of being stopped, the cluster is strongly deformed and attains a roughly pancake shape. Due to the cluster inertia, maximum deformation occurs later than the maximum stopping force. The time scale of projectile stopping is set by t 0 , the time the cluster needs to cover its own diameter before impacting the target; it thus depends on both cluster size and velocity. The time when the cluster experiences its maximum stopping force is around (0.7-0.8)t 0 . We find that the cluster is deformed with huge strain rates of around 1/2t 0 ; this amounts to 10 11 -10 13 s -1 for the cases studied here. (paper)

  14. A light sneutrino rescues the light stop

    Energy Technology Data Exchange (ETDEWEB)

    Chala, M. [Departament de Física Tèorica, Universitat de València and IFIC, Universitat de València-CSIC,Dr. Moliner 50, E-46100 Burjassot (València) (Spain); Delgado, A. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Nardini, G. [Albert Einstein Center (AEC), Institute for Theoretical Physics (ITP), University of Bern,Sidlerstrasse 5, CH-3012 Bern (Switzerland); Quirós, M. [Institut de Física d’Altes Energies (IFAE), The Barcelona Institute of Science and Technology (BIST),Institució Catalana de Recerca i Estudis Avançats - ICREA, Campus UAB, 08193 Bellaterra, Barcelona (Spain)

    2017-04-18

    Stop searches in supersymmetric frameworks with R-parity conservation usually assume the lightest neutralino to be the lightest supersymmetric particle. In this paper we consider an alternative scenario in which the left-handed tau sneutrino is lighter than neutralinos and stable at collider scales, but possibly unstable at cosmological scales. Moreover the (mostly right-handed) stop t̃ is lighter than all electroweakinos, and heavier than the scalars of the third generation lepton doublet, whose charged component, τ̃, is heavier than the neutral one, ν̃. The remaining supersymmetric particles are decoupled from the stop phenomenology. In most of the parameter space, the relevant stop decays are only into tτ̃τ, tν̃ν and bν̃τ via off-shell electroweakinos. We constrain the branching ratios of these decays by recasting the most sensitive stop searches. Due to the “double invisible” kinematics of the t̃→tν̃ν process, and the low efficiency in tagging the tτ̃τ decay products, light stops are generically allowed. In the minimal supersymmetric standard model with ∼ 100 GeV sneutrinos, stops with masses as small as ∼ 350 GeV turn out to be allowed at 95% CL.

  15. Application of the RADTRAN 5 stop model

    International Nuclear Information System (INIS)

    Neuhauser, K.S.; Kanipe, R.L.; Weiner, R.F.

    1997-01-01

    A number of environmental impact analyses with the RADTRAN computer code have shown that dose to persons at stops is one of the largest components of incident-free dose during overland carriage of spent fuel and other radioactive materials (e.g., USDOE, 1994). The input data used in these analyses were taken from a 1983 study that reports actual observations of spent fuel shipments by truck. Early RADTRAN stop models, however, were insufficiently flexible to take advantage of the detailed information in the study. A more recent study of gasoline service stations that specialize in servicing large trucks, which are the most likely stop locations for shipments of Type B packages in the United States, has provided additional, detailed data on refueling/meal stops. The RADTRAN 5 computer code for transportation risk analysis allows exposures at stops to be more fully modeled than have previous releases of the code and is able to take advantage of detailed data. It is the intent of this paper first to compare results from RADTRAN and RADTRAN 5 for the old, low-resolution form of input data, and then to demonstrate what effect the new data and input format have on stop-dose estimates for an individual stop and for a hypothetical shipment route. Finally, these estimated public doses will be contrasted with doses calculated for a special population group -- inspectors

  16. Application of the radtran 5 stop model

    International Nuclear Information System (INIS)

    Neuhauser, K.S.; Kanipe, R.L.; Weiner, R.F.

    1998-01-01

    A number of environmental impact analyzes with the RADTRAN computer code have shown that dose to persons at stops is one of the largest components of incident-free dose during overland carriage of spent fuel and other radioactive materials. The input data used in these analyses were taken from a 1983 study that reports actual observations of spent fuel shipments by truck. Early RADTRAN stop models, however, were insufficiently flexible to take advantage of the detailed information in the study. A more recent study of gasoline service stations that specialize in servicing large trucks, which are the most likely stop locations for shipments of Type B packages in the United States, has provided additional, detailed data on refueling/meal stops. The RADTRAN 5 computer code for transportation risk analysis allows exposures at stops to be more fully modelled than have previous releases of the code and is able to take advantage of detailed data. It is the intent of this paper first to compare results from RADTRAN 4 and RADTRAN 5 for the old, low-resolution form of input data, and then to demonstrate what effect the new data and input format have on stop-dose estimates for an individual stop and for a hypothetical shipment route. Finally, these estimated public doses will be contrasted with doses calculated for a special population group-inspectors. (authors)

  17. PCR-RFLP to Detect Codon 248 Mutation in Exon 7 of "p53" Tumor Suppressor Gene

    Science.gov (United States)

    Ouyang, Liming; Ge, Chongtao; Wu, Haizhen; Li, Suxia; Zhang, Huizhan

    2009-01-01

    Individual genome DNA was extracted fast from oral swab and followed up with PCR specific for codon 248 of "p53" tumor suppressor gene. "Msp"I restriction mapping showed the G-C mutation in codon 248, which closely relates to cancer susceptibility. Students learn the concepts, detection techniques, and research significance of point mutations or…

  18. Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels

    DEFF Research Database (Denmark)

    Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas

    2012-01-01

    The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle a...

  19. Nucleotide composition of the Zika virus RNA genome and its codon usage

    NARCIS (Netherlands)

    van Hemert, Formijn; Berkhout, Ben

    2016-01-01

    RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and

  20. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius

    Directory of Open Access Journals (Sweden)

    Christopher D Johnston

    2014-09-01

    Full Text Available It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of two MAP genes (MAP2121c and MAP3733c can enhance the heterologous expression of two antigens (MMP and MptD respectively, analogous to the form to which they are produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, codon optimised MptD displayed the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adhered with the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne’s disease.

  1. The effect of tRNA levels on decoding times of mRNA codons.

    Science.gov (United States)

    Dana, Alexandra; Tuller, Tamir

    2014-08-01

    The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons decoding time is a fundamental biomedical research question; however, due to a large number of variables affecting this process and the non-direct relation between them, a conclusive answer to this question has eluded so far researchers in the field. In this study, we perform a novel analysis of the ribosome profiling data of four organisms which enables ranking the decoding times of different codons while filtering translational phenomena such as experimental biases, extreme ribosomal pauses and ribosome traffic jams. Based on this filtering, we show for the first time that there is a significant correlation between tRNA concentrations and the codons estimated decoding time both in prokaryotes and in eukaryotes in natural conditions (-0.38 to -0.66, all P values decoding times are not correlated with aminoacyl-tRNA levels. The reported results support the conjecture that translation efficiency is directly influenced by the tRNA levels in the cell. Thus, they should help to understand the evolution of synonymous aspects of coding sequences via the adaptation of their codons to the tRNA pool. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Maximum likelihood estimation of ancestral codon usage bias parameters in Drosophila

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bauer DuMont, Vanessa L; Hubisz, Melissa J

    2007-01-01

    : the selection coefficient for optimal codon usage (S), allowing joint maximum likelihood estimation of S and the dN/dS ratio. We apply the method to previously published data from Drosophila melanogaster, Drosophila simulans, and Drosophila yakuba and show, in accordance with previous results, that the D...

  3. Differential trends in the codon usage patterns in HIV-1 genes.

    Directory of Open Access Journals (Sweden)

    Aridaman Pandit

    Full Text Available Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host-pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level.

  4. An environmental signature for 323 microbial genomes based on codon adaptation indices

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Friis, Carsten; Juncker, Agnieszka

    2006-01-01

    , we show that codon usage preference provides an environmental signature by which it is possible to group bacteria according to their lifestyle, for instance soil bacteria and soil symbionts, spore formers, enteric bacteria, aquatic bacteria, and intercellular and extracellular pathogens. Conclusion...

  5. Tuning protein expression using synonymous codon libraries targeted to the 5' mRNA coding region

    DEFF Research Database (Denmark)

    Goltermann, Lise; Borch Jensen, Martin; Bentin, Thomas

    2011-01-01

    intermediate expression levels of green fluorescent protein in Escherichia coli. At least in one case, no apparent effect on protein stability was observed, pointing to RNA level effects as the principal reason for the observed expression differences. Targeting a synonymous codon library to the 5' coding...

  6. Thrombosis in Hb Taybe [codons 38/39 (-ACC) (α1)

    DEFF Research Database (Denmark)

    Juul, Maja Bech; Vestergaard, Hanne; Petersen, Jesper

    2012-01-01

    Hb Taybe is a highly unstable hemoglobin (Hb) variant caused by a 3 bp deletion at codons 38/39 (-ACC) on the α1-globin gene. We report for the first time, a patient with a compound heterozygosity for Hb Taybe and a 5 bp deletion at the splice donor site of IVS-I on the α2-globin gene and ischemic...

  7. Fidelity of HIS4 start codon selection influences 3-Amino-1,2,4 ...

    Indian Academy of Sciences (India)

    Pankaj Alone

    Fidelity of HIS4 start codon selection influences 3-Amino-1,2,4-Triazole (3AT) .... media in presence or absence of 3AT and harvested at 6000xg at room ..... The overnight cultures were serially diluted (with O.D600 of 0.5, 0.05, 0.005, 0.0005,.

  8. Unassigned Codons, Nonsense Suppression, and Anticodon Modifications in the Evolution of the Genetic Code

    NARCIS (Netherlands)

    P.T.S. van der Gulik (Peter); W.D. Hoff (Wouter)

    2011-01-01

    htmlabstractThe origin of the genetic code is a central open problem regarding the early evolution of life. Here, we consider two undeveloped but important aspects of possible scenarios for the evolutionary pathway of the translation machinery: the role of unassigned codons in early stages

  9. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... figure out how to avoid these situations and develop a plan to stop. Just knowing when you’ ... a doctor. If you bite your nails and develop a skin or nail infection, consult a board- ...

  10. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... your nails to your face and mouth. To help you stop biting your nails, dermatologists recommend the ... stress ball or silly putty instead. This will help keep your hands busy and away from your ...

  11. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... and away from your mouth. Identify your triggers: These could be physical triggers, such as the presence ... nails, you can figure out how to avoid these situations and develop a plan to stop. Just ...

  12. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a dermatologist Why ... how to avoid these situations and develop a plan to stop. Just knowing when you’re inclined ...

  13. Port Authority of Allegheny County Transit Stops

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — All transit stops within the Port Authority of Allegheny County's service area for the November 20, 2016 - March (TBD) 2017 schedule period.

  14. Imagine stopping the progression of Alzheimer's

    Science.gov (United States)

    ... Issue Past Issues Imagine stopping the progression of Alzheimer's Past Issues / Fall 2006 Table of Contents For ... I have friends and loved ones suffering from Alzheimer's. But I can imagine… and hope for… a ...

  15. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Part 2: Origin Part 3: Function Textbook Study notes Image library 3-D animated image library Board ... gradually stop biting your nails: Some doctors recommend taking a gradual approach to break the habit. Try ...

  16. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... Mohs AUC MyDermPath+ Psoriasis Patient education resources Practice Management Center Coding and reimbursement Coding MACRA Fee schedule ... your nails: Some doctors recommend taking a gradual approach to break the habit. Try to stop biting ...

  17. Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

    Science.gov (United States)

    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-04-21

    To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

  18. Decoding options and accuracy of translation of developmentally regulated UUA codon in Streptomyces: bioinformatic analysis.

    Science.gov (United States)

    Rokytskyy, Ihor; Koshla, Oksana; Fedorenko, Victor; Ostash, Bohdan

    2016-01-01

    The gene bldA for leucyl [Formula: see text] is known for almost 30 years as a key regulator of morphogenesis and secondary metabolism in genus Streptomyces. Codon UUA is the rarest one in Streptomyces genomes and is present exclusively in genes with auxiliary functions. Delayed accumulation of translation-competent [Formula: see text] is believed to confine the expression of UUA-containing transcripts to stationary phase. Implicit to the regulatory function of UUA codon is the assumption about high accuracy of its translation, e.g. the latter should not occur in the absence of cognate [Formula: see text]. However, a growing body of facts points to the possibility of mistranslation of UUA-containing transcripts in the bldA-deficient mutants. It is not known what type of near-cognate tRNA(s) may decode UUA in the absence of cognate tRNA in Streptomyces, and whether UUA possesses certain inherent properties (such as increased/decreased accuracy of decoding) that would favor its use for regulatory purposes. Here we took bioinformatic approach to address these questions. We catalogued the entire complement of tRNA genes from several relevant Streptomyces and identified genes for posttranscriptional modifications of tRNA that might be involved in UUA decoding by cognate and near-cognate tRNAs. Based on tRNA gene content in Streptomyces genomes, we propose possible scenarios of UUA codon mistranslation. UUA is not associated with an increased rate of missense errors as compared to other leucyl codons, contrasting general belief that low-abundant codons are more error-prone than the high-abundant ones.

  19. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene

  20. Empirical stopping powers for ions in solids

    International Nuclear Information System (INIS)

    Ziegler, J.F.; Biersack, J.P.; Littmark, U.

    1983-01-01

    The work of Brandt and collaborators on low energy ion stopping powers has been extended to create an empirical formulation for the stopping of ions in solids. The result is a simple computer program (about 60 lines of code) which calculates stopping powers from zero to 100 MeV/amu for all ions in all elemental solids. This code has been compared to the data in about 2000 papers, and has a standard error of 9% for energies above keV/amu. This approach includes high energy relativistic effects and shell-corrections. In the medium energy range it uses stopping theory based on the local-density approximation and Lindhard stopping in a free electron gas. This is applied to realistic Hartree-Fock charge distributions for crystalline solids. In the low energy range it uses the Brandt concepts of ion stripping relative to the Fermi velocity of solids, and also his formalism for the relation of projectile ionization to its effective charge. The details of the calculation are presented, and a broad comparison is shown with experiment. Special comparative examples are shown of both the low energy stopping power oscillations which depend on the atomic number of the ion, and also of the target

  1. Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior.

    Science.gov (United States)

    Ma, Ning; Yu, Angela J

    2016-01-01

    Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1) the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2) an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian) updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination should result in longer go reaction time (RT), lower stop error rate, as well as faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

  2. Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior

    Directory of Open Access Journals (Sweden)

    Ning eMa

    2016-03-01

    Full Text Available Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1 the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2 an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination results in a longer go reaction time (RT, a lower stop error rate, as well as a faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

  3. Stopping, goal-conflict, trait anxiety and frontal rhythmic power in the stop-signal task.

    Science.gov (United States)

    Neo, Phoebe S-H; Thurlow, Jane K; McNaughton, Neil

    2011-12-01

    The medial right frontal cortex is implicated in fast stopping of an initiated motor action in the stop-signal task (SST). To assess whether this region is also involved in the slower behavioural inhibition induced by goal conflict, we tested for effects of goal conflict (when stop and go tendencies are balanced) on low-frequency rhythms in the SST. Stop trials were divided, according to the delays at which the stop signal occurred, into short-, intermediate-, and long-delay trials. Consistent with goal-conflict processing, intermediate-delay trials were associated with greater 7-8 Hz EEG power than short- or long-delay trials at medial right frontal sites (Fz, F4, and F8). At F8, 7-8 Hz power was linked to high trait anxiety and neuroticism. A separate 4-7 Hz power increase was also seen in stop, relative to go, trials, but this was independent of delay, was maximal at the central midline site Cz, and predicted faster stopping. Together with previous data on the SST, these results suggest that the right frontal region could be involved in multiple inhibition mechanisms. We propose a hierarchical model of the control of stopping that integrates the literature on the neural control of fast motor stopping with that on slower, motive-directed behavioural inhibition.

  4. Large-Scale Genomic Analysis of Codon Usage in Dengue Virus and Evaluation of Its Phylogenetic Dependence

    Directory of Open Access Journals (Sweden)

    Edgar E. Lara-Ramírez

    2014-01-01

    Full Text Available The increasing number of dengue virus (DENV genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1–4 (DENV1–4 has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3 as well as the effective number of codons (ENC, ENCp versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA and clustering analysis on relative synonymous codon usage (RSCU within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1–4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution.

  5. Large-Scale Genomic Analysis of Codon Usage in Dengue Virus and Evaluation of Its Phylogenetic Dependence

    Science.gov (United States)

    Lara-Ramírez, Edgar E.; Salazar, Ma Isabel; López-López, María de Jesús; Salas-Benito, Juan Santiago; Sánchez-Varela, Alejandro

    2014-01-01

    The increasing number of dengue virus (DENV) genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1–4 (DENV1–4) has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC) with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3) as well as the effective number of codons (ENC, ENCp) versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA) and clustering analysis on relative synonymous codon usage (RSCU) within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1–4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution. PMID:25136631

  6. Mutations to Less-Preferred Synonymous Codons in a Highly Expressed Gene of Escherichia coli: Fitness and Epistatic Interactions.

    Directory of Open Access Journals (Sweden)

    David J Hauber

    Full Text Available Codon-tRNA coevolution to maximize protein production has been, until recently, the dominant hypothesis to explain codon-usage bias in highly expressed bacterial genes. Two predictions of this hypothesis are 1 selection is weak; and 2 similar silent replacements at different codons should have similar fitness consequence. We used an allele-replacement strategy to change five specific 3rd-codon-position (silent sites in the highly expressed Escherichia coli ribosomal protein gene rplQ from the wild type to a less-preferred alternative. We introduced the five mutations within a 10-codon region. Four of the silent sites were chosen to test the second prediction, with a CTG to CTA mutation being introduced at two closely linked leucine codons and an AAA to AAG mutation being introduced at two closely linked lysine codons. We also introduced a fifth silent mutation, a GTG to GTA mutation at a valine codon in the same genic region. We measured the fitness effect of the individual mutations by competing each single-mutant strain against the parental wild-type strain, using a disrupted form of the araA gene as a selectively neutral phenotypic marker to distinguish between strains in direct competition experiments. Three of the silent mutations had a fitness effect of |s| > 0.02, which is contradictory to the prediction that selection will be weak. The two leucine mutations had significantly different fitness effects, as did the two lysine mutations, contradictory to the prediction that similar mutations at different codons should have similar fitness effects. We also constructed a strain carrying all five silent mutations in combination. Its fitness effect was greater than that predicted from the individual fitness values, suggesting that negative synergistic epistasis acts on the combination allele.

  7. Numeral series hidden in the distribution of atomic mass of amino acids to codon domains in the genetic code.

    Science.gov (United States)

    Wohlin, Åsa

    2015-03-21

    The distribution of codons in the nearly universal genetic code is a long discussed issue. At the atomic level, the numeral series 2x(2) (x=5-0) lies behind electron shells and orbitals. Numeral series appear in formulas for spectral lines of hydrogen. The question here was if some similar scheme could be found in the genetic code. A table of 24 codons was constructed (synonyms counted as one) for 20 amino acids, four of which have two different codons. An atomic mass analysis was performed, built on common isotopes. It was found that a numeral series 5 to 0 with exponent 2/3 times 10(2) revealed detailed congruency with codon-grouped amino acid side-chains, simultaneously with the division on atom kinds, further with main 3rd base groups, backbone chains and with codon-grouped amino acids in relation to their origin from glycolysis or the citrate cycle. Hence, it is proposed that this series in a dynamic way may have guided the selection of amino acids into codon domains. Series with simpler exponents also showed noteworthy correlations with the atomic mass distribution on main codon domains; especially the 2x(2)-series times a factor 16 appeared as a conceivable underlying level, both for the atomic mass and charge distribution. Furthermore, it was found that atomic mass transformations between numeral systems, possibly interpretable as dimension degree steps, connected the atomic mass of codon bases with codon-grouped amino acids and with the exponent 2/3-series in several astonishing ways. Thus, it is suggested that they may be part of a deeper reference system. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  8. Bubble formation after a 20-m dive: deep-stop vs. shallow-stop decompression profiles

    NARCIS (Netherlands)

    Schellart, Nico A. M.; Corstius, Jan-Jaap Brandt; Germonpré, Peter; Sterk, Wouter

    2008-01-01

    OBJECTIVES: It is claimed that performing a "deep stop," a stop at about half of maximal diving depth (MDD), can reduce the amount of detectable precordial bubbles after the dive and may thus diminish the risk of decompression sickness. In order to ascertain whether this reduction is caused by the

  9. Improved production of membrane proteins in Escherichia coli by selective codon substitutions

    DEFF Research Database (Denmark)

    Nørholm, Morten H.H.; Toddo, Stephen; Virkki, Minttu T.I.

    2013-01-01

    Membrane proteins are extremely challenging to produce in sufficient quantities for biochemical and structural analysis and there is a growing demand for solutions to this problem. In this study we attempted to improve expression of two difficult-to-express coding sequences (araH and narK) for me......Membrane proteins are extremely challenging to produce in sufficient quantities for biochemical and structural analysis and there is a growing demand for solutions to this problem. In this study we attempted to improve expression of two difficult-to-express coding sequences (araH and nar......K) for membrane transporters. For both coding sequences, synonymous codon substitutions in the region adjacent to the AUG start led to significant improvements in expression, whereas multi-parameter sequence optimization of codons throughout the coding sequence failed. We conclude that coding sequences can be re...

  10. The extent of the stop coannihilation strip

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, John [King' s College London, Theoretical Particle Physics and Cosmology Group, Department of Physics, London (United Kingdom); CERN, Theory Division, Geneva 23 (Switzerland); Olive, Keith A. [University of Minnesota, School of Physics and Astronomy, Minneapolis, MN (United States); University of Minnesota, William I. Fine Theoretical Physics Institute, School of Physics and Astronomy, Minneapolis, MN (United States); Zheng, Jiaming [University of Minnesota, School of Physics and Astronomy, Minneapolis, MN (United States)

    2014-07-15

    Many supersymmetric models such as the constrained minimal supersymmetric extension of the Standard Model (CMSSM) feature a strip in parameter space where the lightest neutralino χ is identified as the lightest supersymmetric particle, the lighter stop squark t{sub 1} is the next-to-lightest supersymmetric particle (NLSP), and the relic χ cold darkmatter density is brought into the range allowed by astrophysics and cosmology by coannihilation with the lighter stop squark t{sub 1} NLSP. We calculate the stop coannihilation strip in the CMSSM, incorporating Sommerfeld enhancement effects, and we explore the relevant phenomenological constraints and phenomenological signatures. In particular, we show that the t{sub 1} may weigh several TeV, and its lifetime may be in the nanosecond range, features that are more general than the specific CMSSM scenarios that we study in this paper. (orig.)

  11. The stopping rules for winsorized tree

    Science.gov (United States)

    Ch'ng, Chee Keong; Mahat, Nor Idayu

    2017-11-01

    Winsorized tree is a modified tree-based classifier that is able to investigate and to handle all outliers in all nodes along the process of constructing the tree. It overcomes the tedious process of constructing a classical tree where the splitting of branches and pruning go concurrently so that the constructed tree would not grow bushy. This mechanism is controlled by the proposed algorithm. In winsorized tree, data are screened for identifying outlier. If outlier is detected, the value is neutralized using winsorize approach. Both outlier identification and value neutralization are executed recursively in every node until predetermined stopping criterion is met. The aim of this paper is to search for significant stopping criterion to stop the tree from further splitting before overfitting. The result obtained from the conducted experiment on pima indian dataset proved that the node could produce the final successor nodes (leaves) when it has achieved the range of 70% in information gain.

  12. Electron stopping powers for transport calculations

    International Nuclear Information System (INIS)

    Berger, M.J.

    1988-01-01

    The reliability of radiation transport calculations depends on the accuracy of the input cross sections. Therefore, it is essential to review and update the cross sections from time to time. Even though the main interest of the author's group at NBS is in transport calculations and their applications, the group spends almost as much time on the analysis and preparation of cross sections as on the development of transport codes. Stopping powers, photon attenuation coefficients, bremsstrahlung cross sections, and elastic-scattering cross sections in recent years have claimed attention. This chapter deals with electron stopping powers (with emphasis on collision stopping powers), and reviews the state of the art as reflected by Report 37 of the International Commission on Radiation Units and Measurements

  13. Codon size reduction as the origin of the triplet genetic code.

    Directory of Open Access Journals (Sweden)

    Pavel V Baranov

    Full Text Available The genetic code appears to be optimized in its robustness to missense errors and frameshift errors. In addition, the genetic code is near-optimal in terms of its ability to carry information in addition to the sequences of encoded proteins. As evolution has no foresight, optimality of the modern genetic code suggests that it evolved from less optimal code variants. The length of codons in the genetic code is also optimal, as three is the minimal nucleotide combination that can encode the twenty standard amino acids. The apparent impossibility of transitions between codon sizes in a discontinuous manner during evolution has resulted in an unbending view that the genetic code was always triplet. Yet, recent experimental evidence on quadruplet decoding, as well as the discovery of organisms with ambiguous and dual decoding, suggest that the possibility of the evolution of triplet decoding from living systems with non-triplet decoding merits reconsideration and further exploration. To explore this possibility we designed a mathematical model of the evolution of primitive digital coding systems which can decode nucleotide sequences into protein sequences. These coding systems can evolve their nucleotide sequences via genetic events of Darwinian evolution, such as point-mutations. The replication rates of such coding systems depend on the accuracy of the generated protein sequences. Computer simulations based on our model show that decoding systems with codons of length greater than three spontaneously evolve into predominantly triplet decoding systems. Our findings suggest a plausible scenario for the evolution of the triplet genetic code in a continuous manner. This scenario suggests an explanation of how protein synthesis could be accomplished by means of long RNA-RNA interactions prior to the emergence of the complex decoding machinery, such as the ribosome, that is required for stabilization and discrimination of otherwise weak triplet codon

  14. Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli

    OpenAIRE

    Shakhnovich, Eugene; Zhang, Wenli; Yan, Jin; Adkar, Bharat; Jacobs, William; Bhattacharyya, Sanchari; Adkar, Bharat

    2018-01-01

    Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further ...

  15. Genome-wide analysis of codon usage bias in Bovine Coronavirus

    OpenAIRE

    Castells, Mat?as; Victoria, Mat?as; Colina, Rodney; Musto, H?ctor; Cristina, Juan

    2017-01-01

    Background Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host?s immune system and evolution. Methods We performed a comprehensive analysis of co...

  16. CodonShuffle: a tool for generating and analyzing synonymously mutated sequences

    OpenAIRE

    Jorge, Daniel Macedo de Melo; Mills, Ryan E.; Lauring, Adam S.

    2015-01-01

    Because synonymous mutations do not change the amino acid sequence of a protein, they are generally considered to be selectively neutral. Empiric data suggest, however, that a significant fraction of viral mutational fitness effects may be attributable to synonymous mutation. Bias in synonymous codon usage in viruses may result from selection for translational efficiency, mutational bias, base pairing requirements in RNA structures, or even selection against specific dinucleotides by innate i...

  17. GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene

    Czech Academy of Sciences Publication Activity Database

    Dubot, A.; Godinot, C.; Dumur, V.; Sablonniere, B.; Stojkovic, T.; Cuisset, J. M.; Vojtíšková, Alena; Pecina, Petr; Ješina, Pavel; Houštěk, Josef

    2004-01-01

    Roč. 313, č. 3 (2004), s. 687-693 ISSN 0006-291X R&D Projects: GA MŠk LN00A079; GA MZd NE6533 Grant - others:Fondation Jerome LeJeune(XE) Grant project; GA-(FR) CNRS; GA-(FR) Rhone Alpes Region Institutional research plan: CEZ:AV0Z5011922 Keywords : GUG initiation codon * ATP6 gene * mitochondrial diseases Subject RIV: CE - Biochemistry Impact factor: 2.904, year: 2004

  18. Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

    Directory of Open Access Journals (Sweden)

    Sylvia Michelina Fernandes Brenna

    2004-01-01

    Full Text Available The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67% of 148 women were found to be homozygous (arg/arg for the arginine polymorphism, and 49 (33% were heterozygous (arg/pro. This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis.

  19. Two cloned β thalassemia genes are associated with amber mutations at codon 39

    Science.gov (United States)

    Pergolizzi, Robert; Spritz, Richard A.; Spence, Sally; Goossens, Michel; Kan, Yuet Wai; Bank, Arthur

    1981-01-01

    Two β globin genes from patients with the β+ thalassemia phenotype have been cloned and sequenced. A single nucleotide change from CAG to TAG (an amber mutation) at codon 39 is the only difference from normal in both genes analyzed. The results are consistent with the assumption that both patients are doubly heterozygous for β+ and β° thalassemia, and that we have isolated and analyzed the β° thalassemia gene. Images PMID:6278453

  20. Stopping Power Measurements: Implications in Nuclear Astrophysics

    International Nuclear Information System (INIS)

    Carmen Angulo; Thierry Delbar; Jean-Sebastien Graulich; Pierre Leleux

    1999-01-01

    The stopping powers of C, CH 2 , Al, Ni, and polyvinylchloride (PVC) for several light ions ( 9 Be, 11 B, 12 C, 14 N, 16 O, 19 F, 20 Ne) with an incident energy of 1 MeV/amu have been measured at the Louvain-la-Neuve cyclotron facility. Stopping powers are given relative to the one for 5.5 MeV 4 He ions with an uncertainty of less than 1%. We compare our results with two widely used semiempirical models and we discuss some implications in nuclear astrophysics studies

  1. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius.

    Science.gov (United States)

    Johnston, Christopher D; Bannantine, John P; Govender, Rodney; Endersen, Lorraine; Pletzer, Daniel; Weingart, Helge; Coffey, Aidan; O'Mahony, Jim; Sleator, Roy D

    2014-01-01

    It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease.

  2. Mutations at the cysteine codons of the recA gene of Escherichia coli

    International Nuclear Information System (INIS)

    Weisemann, J.M.; Weinstock, G.M.

    1988-01-01

    Each of the three cysteine residues in the Escherichia coli RecA protein was replaced with a number of other amino acids. To do this, each cysteine codon was first converted to a chain-terminating amber codon by oligonucleotide-directed mutagenesis. These amber mutants were then either assayed for function in different suppressor strains or reverted by a second round of mutagenesis with oligonucleotides that had random sequences at the amber codon. Thirty-three different amino acid substitutions were obtained. Mutants were tested for three functions of RecA: survival following UV irradiation, homologous recombination, and induction of the SOS response. It was found that although none of the cysteines is essential for activity, mutations at each of these positions can affect one or more of the activities of RecA, depending on the particular amino acid substitution. In addition, the cysteine at position 116 appears to be involved in the RecA-promoted cleavage of the LexA protein

  3. Genotyping of K-ras codons 12 and 13 mutations in colorectal cancer by capillary electrophoresis.

    Science.gov (United States)

    Chen, Yen-Ling; Chang, Ya-Sian; Chang, Jan-Gowth; Wu, Shou-Mei

    2009-06-26

    Point mutations of the K-ras gene located in codons 12 and 13 cause poor responses to the anti-epidermal growth factor receptor (anti-EGFR) therapy of colorectal cancer (CRC) patients. Besides, mutations of K-ras gene have also been proven to play an important role in human tumor progression. We established a simple and effective capillary electrophoresis (CE) method for simultaneous point mutation detection in codons 12 and 13 of K-ras gene. We combined one universal fluorescence-based nonhuman-sequence primer and two fragment-oriented primers in one tube, and performed this two-in-one polymerase chain reaction (PCR). PCR fragments included wild type and seven point mutations at codons 12 and 13 of K-ras gene. The amplicons were analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE analysis was performed by using a 1x Tris-borate-EDTA (TBE) buffer containing 1.5% (w/v) hydroxyethylcellulose (HEC) (MW 250,000) under reverse polarity with 15 degrees C and 30 degrees C. Ninety colorectal cancer patients were blindly genotyped using this developed method. The results showed good agreement with those of DNA sequencing method. The SSCP-CE was feasible for mutation screening of K-ras gene in populations.

  4. Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome.

    Science.gov (United States)

    Neuhaus, Christine; Eisenberger, Tobias; Decker, Christian; Nagl, Sandra; Blank, Cornelia; Pfister, Markus; Kennerknecht, Ingo; Müller-Hofstede, Cornelie; Charbel Issa, Peter; Heller, Raoul; Beck, Bodo; Rüther, Klaus; Mitter, Diana; Rohrschneider, Klaus; Steinhauer, Ute; Korbmacher, Heike M; Huhle, Dagmar; Elsayed, Solaf M; Taha, Hesham M; Baig, Shahid M; Stöhr, Heidi; Preising, Markus; Markus, Susanne; Moeller, Fabian; Lorenz, Birgit; Nagel-Wolfrum, Kerstin; Khan, Arif O; Bolz, Hanno J

    2017-09-01

    Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3 , genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.

  5. Evaluating the Effects of Traffic on Driver Stopping and Turn Signal Use at a Stop Sign: A Systematic Replication

    Science.gov (United States)

    Lebbon, Angela R.; Austin, John; Van Houten, Ron; Malenfant, Louis E.

    2007-01-01

    The current analyses of observational data found that oncoming traffic substantially affected driver stopping patterns and turn signal use at the target stop sign. The percentage of legal stops and turn signal use by drivers in the presence and absence of traffic was analyzed using a multi-element design. The results showed that legal stops were…

  6. Seismic stops for nuclear power plants

    International Nuclear Information System (INIS)

    Cloud, R.L.; Leung, J.S.M.; Anderson, P.H.

    1989-01-01

    In the regulated world of nuclear power, the need to have analytical proof of performance in hypothetical design-basis events such as earth quakes has placed a premium on design configurations that are mathematically tractable and easily analyzed. This is particularly true for the piping design. Depending on how the piping analyses are organized and on how old the plant is, there may be from 200 to 1000 separate piping runs to be designed, analyzed, and qualified. In this situation, the development of snubbers seemed like the answer to a piping engineer's prayer. At any place where seismic support was required but thermal motion had to be accommodated, a snubber could be specified. But, as experience has now shown, the program was solved only on paper. This article presents an alternative to conventional snubbers. These new devices, termed Seismic Stops are designed to replace snubbers directly and look like snubbers on the outside. But their design is based on a completely different principle. The original concept has adapted from early seismic-resistant pipe support designs used on fossil power plants in California. The fundamental idea is to provide a space envelope in which the pipe can expand freely between the hot and cold positions, but cannot move outside the envelope. Seismic Stops are designed to transmit any possible impact load, as would occur in an earthquake, away from the pipe itself to the Seismic Stop. The Seismic Stop pipe support is shown

  7. Are Stopped Strings Preferred in Sad Music?

    Directory of Open Access Journals (Sweden)

    David Huron

    2017-01-01

    Full Text Available String instruments may be played either with open strings (where the string vibrates between the bridge and a hard wooden nut or with stopped strings (where the string vibrates between the bridge and a performer's finger pressed against the fingerboard. Compared with open strings, stopped strings permit the use of vibrato and exhibit a darker timbre. Inspired by research on the timbre of sad speech, we test whether there is a tendency to use stopped strings in nominally sad music. Specifically, we compare the proportion of potentially open-to-stopped strings in a sample of slow, minor-mode movements with matched major-mode movements. By way of illustration, a preliminary analysis of Samuel Barber's famous Adagio from his Opus 11 string quartet shows that the selected key (B-flat minor provides the optimum key for minimizing open string tones. However, examination of a broader controlled sample of quartet movements by Haydn, Mozart and Beethoven failed to exhibit the conjectured relationship. Instead, major-mode movements were found to avoid possible open strings more than slow minor-mode movements.

  8. How to Stop Biting Your Nails

    Medline Plus

    Full Text Available ... gloves to prevent biting. Replace the nail-biting habit with a good habit: When you feel like biting your nails, try ... recommend taking a gradual approach to break the habit. Try to stop biting one set of nails, ...

  9. Car Stopping Distance on a Tabletop

    Science.gov (United States)

    Haugland, Ole Anton

    2013-01-01

    Stopping distances in car braking can be an intriguing topic in physics teaching. It illustrates some basic principles of physics, and sheds valuable light on students' attitude towards aggressive driving. Due to safety considerations, it can be difficult to make experiments with actual car braking. (Contains 2 figures.)

  10. Bystanders Are the Key to Stopping Bullying

    Science.gov (United States)

    Padgett, Sharon; Notar, Charles E.

    2013-01-01

    Bullying is the dominance over another. Bullying occurs when there is an audience. Peer bystanders provide an audience 85% of instances of bullying. If you remove the audience bullying should stop. The article is a review of literature (2002-2013) on the role of bystanders; importance of bystanders; why bystanders behave as they do; resources to…

  11. Brownian Optimal Stopping and Random Walks

    International Nuclear Information System (INIS)

    Lamberton, D.

    2002-01-01

    One way to compute the value function of an optimal stopping problem along Brownian paths consists of approximating Brownian motion by a random walk. We derive error estimates for this type of approximation under various assumptions on the distribution of the approximating random walk

  12. Approximations for stop-loss reinsurance premiums

    NARCIS (Netherlands)

    Reijnen, Rajko; Albers, Willem/Wim; Kallenberg, W.C.M.

    2005-01-01

    Various approximations of stop-loss reinsurance premiums are described in literature. For a wide variety of claim size distributions and retention levels, such approximations are compared in this paper to each other, as well as to a quantitative criterion. For the aggregate claims two models are

  13. Stop-loss premiums under dependence

    NARCIS (Netherlands)

    Albers, Willem/Wim

    1999-01-01

    Stop-loss premiums are typically calculated under the assumption that the insured lives in the underlying portfolio are independent. Here we study the effects of small departures from this assumption. Using Edgeworth expansions, it is made transparent which configurations of dependence parameters

  14. Ab initio electronic stopping power in materials

    International Nuclear Information System (INIS)

    Shukri, Abdullah-Atef

    2015-01-01

    The average energy loss of an ion per unit path length when it is moving through the matter is named the stopping power. The knowledge of the stopping power is essential for a variety of contemporary applications which depend on the transport of ions in matter, especially ion beam analysis techniques and ion implantation. Most noticeably, the use of proton or heavier ion beams in radiotherapy requires the knowledge of the stopping power. Whereas experimental data are readily available for elemental solids, the data are much more scarce for compounds. The linear response dielectric formalism has been widely used in the past to study the electronic stopping power. In particular, the famous pioneering calculations due to Lindhard evaluate the electronic stopping power of a free electron gas. In this thesis, we develop a fully ab initio scheme based on linear response time-dependent density functional theory to predict the impact parameter averaged quantity named the random electronic stopping power (RESP) of materials without any empirical fitting. The purpose is to be capable of predicting the outcome of experiments without any knowledge of target material besides its crystallographic structure. Our developments have been done within the open source ab initio code named ABINIT, where two approximations are now available: the Random-Phase Approximation (RPA) and the Adiabatic Local Density Approximation (ALDA). Furthermore, a new method named 'extrapolation scheme' have been introduced to overcome the stringent convergence issues we have encountered. These convergence issues have prevented the previous studies in literature from offering a direct comparison to experiment. First of all, we demonstrate the importance of describing the realistic ab initio electronic structure by comparing with the historical Lindhard stopping power evaluation. Whereas the Lindhard stopping power provides a first order description that captures the general features of the

  15. Codon optimisation to improve expression of a Mycobacterium avium ssp. paratuberculosis-specific membrane-associated antigen by Lactobacillus salivarius.

    Science.gov (United States)

    Johnston, Christopher; Douarre, Pierre E; Soulimane, Tewfik; Pletzer, Daniel; Weingart, Helge; MacSharry, John; Coffey, Aidan; Sleator, Roy D; O'Mahony, Jim

    2013-06-01

    Subunit and DNA-based vaccines against Mycobacterium avium ssp. paratuberculosis (MAP) attempt to overcome inherent issues associated with whole-cell formulations. However, these vaccines can be hampered by poor expression of recombinant antigens from a number of disparate hosts. The high G+C content of MAP invariably leads to a codon bias throughout gene expression. To investigate if the codon bias affects recombinant MAP antigen expression, the open reading frame of a MAP-specific antigen MptD (MAP3733c) was codon optimised for expression against a Lactobacillus salivarius host. Of the total 209 codons which constitute MAP3733c, 172 were modified resulting in a reduced G+C content from 61% for the native gene to 32.7% for the modified form. Both genes were placed under the transcriptional control of the PnisA promoter; allowing controlled heterologous expression in L. salivarius. Expression was monitored using fluorescence microscopy and microplate fluorometry via GFP tags translationally fused to the C-termini of the two MptD genes. A > 37-fold increase in expression was observed for the codon-optimised MAP3733synth variant over the native gene. Due to the low cost and improved expression achieved, codon optimisation significantly improves the potential of L. salivarius as an oral vaccine stratagem against Johne's disease. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  16. Comparative analysis of codon usage patterns and identification of predicted highly expressed genes in five Salmonella genomes

    Directory of Open Access Journals (Sweden)

    Mondal U

    2008-01-01

    Full Text Available Purpose: To anlyse codon usage patterns of five complete genomes of Salmonella , predict highly expressed genes, examine horizontally transferred pathogenicity-related genes to detect their presence in the strains, and scrutinize the nature of highly expressed genes to infer upon their lifestyle. Methods: Protein coding genes, ribosomal protein genes, and pathogenicity-related genes were analysed with Codon W and CAI (codon adaptation index Calculator. Results: Translational efficiency plays a role in codon usage variation in Salmonella genes. Low bias was noticed in most of the genes. GC3 (guanine cytosine at third position composition does not influence codon usage variation in the genes of these Salmonella strains. Among the cluster of orthologous groups (COGs, translation, ribosomal structure biogenesis [J], and energy production and conversion [C] contained the highest number of potentially highly expressed (PHX genes. Correspondence analysis reveals the conserved nature of the genes. Highly expressed genes were detected. Conclusions: Selection for translational efficiency is the major source of variation of codon usage in the genes of Salmonella . Evolution of pathogenicity-related genes as a unit suggests their ability to infect and exist as a pathogen. Presence of a lot of PHX genes in the information and storage-processing category of COGs indicated their lifestyle and revealed that they were not subjected to genome reduction.

  17. Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.

    Science.gov (United States)

    Babbitt, Gregory A; Alawad, Mohammed A; Schulze, Katharina V; Hudson, André O

    2014-01-01

    While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Lifespan changes in global and selective stopping and performance adjustments

    Directory of Open Access Journals (Sweden)

    Maria Christina Van De Laar

    2011-12-01

    Full Text Available This study examined stopping and performance adjustments in four age groups (M ages: 8, 12, 21, and 76 years. All participants performed on three tasks, a standard two-choice task and the same task in which stop-signal trials were inserted requiring either the suppression of the response activated by the choice stimulus (global stop task or the suppression of the response when one stop signal was presented but not when the other stop signal occurred (selective stop task. The results showed that global stopping was faster than selective stopping in all age groups. Global stopping matured more rapidly than selective stopping. The developmental gain in stopping was considerably more pronounced compared to the loss observed during senescence. All age groups slowed the response on trials without a stop signal in the stop task compared to trials in the choice task, the elderly in particular. In addition, all age groups slowed on trials following stop-signal trials, except the elderly who did not slow following successful inhibits. By contrast, the slowing following failed inhibits was disproportionally larger in the elderly compared to young adults. Finally, sequential effects did not alter the pattern of performance adjustments. The results were interpreted in terms of developmental change in the balance between proactive and reactive control.

  19. Lifespan Changes in Global and Selective Stopping and Performance Adjustments

    Science.gov (United States)

    van de Laar, Maria C.; van den Wildenberg, Wery P. M.; van Boxtel, Geert J. M.; van der Molen, Maurits W.

    2011-01-01

    This study examined stopping and performance adjustments in four age groups (M ages: 8, 12, 21, and 76 years). All participants performed on three tasks, a standard two-choice task and the same task in which stop-signal trials were inserted requiring either the suppression of the response activated by the choice stimulus (global stop task) or the suppression of the response when one stop-signal was presented but not when the other stop-signal occurred (selective stop task). The results showed that global stopping was faster than selective stopping in all age groups. Global stopping matured more rapidly than selective stopping. The developmental gain in stopping was considerably more pronounced compared to the loss observed during senescence. All age groups slowed the response on trials without a stop-signal in the stop task compared to trials in the choice task, the elderly in particular. In addition, all age groups slowed on trials following stop-signal trials, except the elderly who did not slow following successful inhibits. By contrast, the slowing following failed inhibits was disproportionally larger in the elderly compared to young adults. Finally, sequential effects did not alter the pattern of performance adjustments. The results were interpreted in terms of developmental change in the balance between proactive and reactive control. PMID:22180746

  20. Stop feeling: Inhibition of emotional interference following stop-signal trials

    OpenAIRE

    Eyal eKalanthroff; Noga eCohen; Avishai eHenik

    2013-01-01

    Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop...

  1. Simulations of enhanced ion stopping power experiments

    International Nuclear Information System (INIS)

    Mehlhorn, T.A.; Maenchen, J.E.; Olsen, J.N.; Johnson, D.J.

    1984-01-01

    As the material in an ICF target is heated and ionized by an intense ion beam, the ion stopping power changes from that of neutral atoms. This changes the energy deposition characteristics of the ion beam and thereby can profoundly influence the target dynamics. An accurate ion energy deposition model is important for designing ICF targets that perform in an optimal fashion. An experiment to measure a time-resolved ion stopping power history in a partially ionized target is being fielded on the PROTO I accelerator at Sandia Labs. This experiment utilizes a voltage ramped Thomson parabola to provide a time-history of the ion energy incident upon and exiting from a cylindrical target foil

  2. Measurement of stopping power of light ions

    International Nuclear Information System (INIS)

    Sakamoto, Naoki

    1981-01-01

    The stopping power of light ions penetrating various materials has been measured. The data of proton stopping power and the mean ionization potentials are presented. The experiments were made by using the 6.75 MeV protons from a cyclotron and the protons in the energy range from 3 to 9 MeV from a tandem Van de Graaff. The windows with and without sample-foils were rotated in front of a semiconductor detector, and the measured energy loss and the thickness of the sample foils were used to estimate the energy loss at the mean energy of protons in the samples. The analyses were made by considering the inner shell correction, Z 1 3 correction and the Bloch correction. The mean ionization potentials were derived from the data. (Kato, T.)

  3. Nuclear stopping power at high energies

    International Nuclear Information System (INIS)

    Date, S.; Gyulassy, M.; Sumiyoshi, H.

    1985-03-01

    Recent p + A → p + X data are analyzed within the context of the multi-chain and additive quark models. We deduce the average energy loss of a baryon as a function of distance traversed in nuclear matter. Consistency of the multi-chain model is checked by comparing the predictions for p + A → π +- + X with data. We discuss the space-time development of baryon stopping and show how longitudinal growth limits the energy deposition per unit length. Predictions are made for the proton spectra to be measured in nucleus-nucleus collisions at CERN and BNL. Finally, we conclude that the stopping domain for central collisions of heavy ions extends up to center of mass kinetic energies KEsub(em) asymptotically equals 3 +- 1 AGev. (author)

  4. Single start multiple stop time digitizer

    International Nuclear Information System (INIS)

    Deshpande, P.A.; Mukhopadhyay, P.K.; Gopalakrishnan, K.R.

    1997-01-01

    A single start multiple stop time digitizer has been developed which can digitize the time between a start pulse and multiple stop pulses. The system has been designed as a PC add on card. The resolution of the instrument is 10 nSecs and the maximum length of time that it can measure is 1.28 milliseconds. Apart from time digitization, it can also resolve the height of the incoming pulses into 64 levels. After each input pulse the system dead time is less than 300 nSecs. The driver software for this card has been developed on DOS platform. It uses graphical user interface to provide a user friendly environment. The system is intended to be used in time of flight mass spectroscopy experiments. It can also be used for time of flight experiments in nuclear physics. (author). 2 figs

  5. Comparative Mitogenomics of Plant Bugs (Hemiptera: Miridae): Identifying the AGG Codon Reassignments between Serine and Lysine

    Science.gov (United States)

    Wang, Pei; Song, Fan; Cai, Wanzhi

    2014-01-01

    Insect mitochondrial genomes are very important to understand the molecular evolution as well as for phylogenetic and phylogeographic studies of the insects. The Miridae are the largest family of Heteroptera encompassing more than 11,000 described species and of great economic importance. For better understanding the diversity and the evolution of plant bugs, we sequence five new mitochondrial genomes and present the first comparative analysis of nine mitochondrial genomes of mirids available to date. Our result showed that gene content, gene arrangement, base composition and sequences of mitochondrial transcription termination factor were conserved in plant bugs. Intra-genus species shared more conserved genomic characteristics, such as nucleotide and amino acid composition of protein-coding genes, secondary structure and anticodon mutations of tRNAs, and non-coding sequences. Control region possessed several distinct characteristics, including: variable size, abundant tandem repetitions, and intra-genus conservation; and was useful in evolutionary and population genetic studies. The AGG codon reassignments were investigated between serine and lysine in the genera Adelphocoris and other cimicomorphans. Our analysis revealed correlated evolution between reassignments of the AGG codon and specific point mutations at the antidocons of tRNALys and tRNASer(AGN). Phylogenetic analysis indicated that mitochondrial genome sequences were useful in resolving family level relationship of Cimicomorpha. Comparative evolutionary analysis of plant bug mitochondrial genomes allowed the identification of previously neglected coding genes or non-coding regions as potential molecular markers. The finding of the AGG codon reassignments between serine and lysine indicated the parallel evolution of the genetic code in Hemiptera mitochondrial genomes. PMID:24988409

  6. Cloning, Codon Optimization, and Expression of Yersinia intermedia Phytase Gene in E. coli.

    Science.gov (United States)

    Mirzaei, Maryam; Saffar, Behnaz; Shareghi, Behzad

    2016-06-01

    Phytate is an anti-nutritional factor in plants, which catches the most phosphorus contents and some vital minerals. Therefore, Phytase is added mainly as an additive to the monogastric animals' foods to hydrolyze phytate and increase absorption of phosphorus. Y. intermedia phytase is a new phytase with special characteristics such as high specific activity, pH stability, and thermostability. Our aim was to clone, express, and characterizea codon optimized Y. intermedia phytase gene in E. coli . The Y. intermedia phytase gene was optimized according to the codon usage in E. coli . The sequence was synthesized and sub-cloned in pET-22b (+) vector and transformed into E. coli Bl21 (DE3). The protein was expressed in the presence of IPTG at a final concentration of 1 mM at 30°C. The purification of recombinant protein was performed by Ni 2+ affinity chromatography. Phytase activity and stability were determined in various pH and temperatures. The codon optimized Y. intermedia phytase gene was sub-cloned successfully.The expression was confirmed by SDS-PAGE and Western blot analysis. The recombinant enzyme (approximately 45 kDa) was purified. Specific activity of enzyme was 3849 (U.mg -1 ) with optimal pH 5 and optimal temperature of 55°C. Thermostability (80°C for 15 min) and pH stability (3-6) of the enzyme were 56 and more than 80%, respectively. The results of the expression and enzyme characterization revealed that the optimized Y. intermedia phytase gene has a good potential to be produced commercially andto be applied in animals' foodsindustry.

  7. Local synteny and codon usage contribute to asymmetric sequence divergence of Saccharomyces cerevisiae gene duplicates

    Directory of Open Access Journals (Sweden)

    Bergthorsson Ulfar

    2011-09-01

    Full Text Available Abstract Background Duplicated genes frequently experience asymmetric rates of sequence evolution. Relaxed selective constraints and positive selection have both been invoked to explain the observation that one paralog within a gene-duplicate pair exhibits an accelerated rate of sequence evolution. In the majority of studies where asymmetric divergence has been established, there is no indication as to which gene copy, ancestral or derived, is evolving more rapidly. In this study we investigated the effect of local synteny (gene-neighborhood conservation and codon usage on the sequence evolution of gene duplicates in the S. cerevisiae genome. We further distinguish the gene duplicates into those that originated from a whole-genome duplication (WGD event (ohnologs versus small-scale duplications (SSD to determine if there exist any differences in their patterns of sequence evolution. Results For SSD pairs, the derived copy evolves faster than the ancestral copy. However, there is no relationship between rate asymmetry and synteny conservation (ancestral-like versus derived-like in ohnologs. mRNA abundance and optimal codon usage as measured by the CAI is lower in the derived SSD copies relative to ancestral paralogs. Moreover, in the case of ohnologs, the faster-evolving copy has lower CAI and lowered expression. Conclusions Together, these results suggest that relaxation of selection for codon usage and gene expression contribute to rate asymmetry in the evolution of duplicated genes and that in SSD pairs, the relaxation of selection stems from the loss of ancestral regulatory information in the derived copy.

  8. E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI

    Directory of Open Access Journals (Sweden)

    Garcia-Vallvé Santiago

    2008-01-01

    Full Text Available Abstract Background The Codon Adaptation Index (CAI is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values. Results The E-CAI server, available at http://genomes.urv.es/CAIcal/E-CAI, is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated. Conclusion The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences.

  9. Insight into pattern of codon biasness and nucleotide base usage in serotonin receptor gene family from different mammalian species.

    Science.gov (United States)

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

    5-HT (5-Hydroxy-tryptamine) or serotonin receptors are found both in central and peripheral nervous system as well as in non-neuronal tissues. In the animal and human nervous system, serotonin produces various functional effects through a variety of membrane bound receptors. In this study, we focus on 5-HT receptor family from different mammals and examined the factors that account for codon and nucleotide usage variation. A total of 110 homologous coding sequences from 11 different mammalian species were analyzed using relative synonymous codon usage (RSCU), correspondence analysis (COA) and hierarchical cluster analysis together with nucleotide base usage frequency of chemically similar amino acid codons. The mean effective number of codon (ENc) value of 37.06 for 5-HT(6) shows very high codon bias within the family and may be due to high selective translational efficiency. The COA and Spearman's rank correlation reveals that the nucleotide compositional mutation bias as the major factors influencing the codon usage in serotonin receptor genes. The hierarchical cluster analysis suggests that gene function is another dominant factor that affects the codon usage bias, while species is a minor factor. Nucleotide base usage was reported using Goldman, Engelman, Stietz (GES) scale reveals the presence of high uracil (>45%) content at functionally important hydrophobic regions. Our in silico approach will certainly help for further investigations on critical inference on evolution, structure, function and gene expression aspects of 5-HT receptors family which are potential antipsychotic drug targets. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Genetic and codon usage bias analyses of polymerase genes of equine influenza virus and its relation to evolution.

    Science.gov (United States)

    Bera, Bidhan Ch; Virmani, Nitin; Kumar, Naveen; Anand, Taruna; Pavulraj, S; Rash, Adam; Elton, Debra; Rash, Nicola; Bhatia, Sandeep; Sood, Richa; Singh, Raj Kumar; Tripathi, Bhupendra Nath

    2017-08-23

    Equine influenza is a major health problem of equines worldwide. The polymerase genes of influenza virus have key roles in virus replication, transcription, transmission between hosts and pathogenesis. Hence, the comprehensive genetic and codon usage bias of polymerase genes of equine influenza virus (EIV) were analyzed to elucidate the genetic and evolutionary relationships in a novel perspective. The group - specific consensus amino acid substitutions were identified in all polymerase genes of EIVs that led to divergence of EIVs into various clades. The consistent amino acid changes were also detected in the Florida clade 2 EIVs circulating in Europe and Asia since 2007. To study the codon usage patterns, a total of 281,324 codons of polymerase genes of EIV H3N8 isolates from 1963 to 2015 were systemically analyzed. The polymerase genes of EIVs exhibit a weak codon usage bias. The ENc-GC3s and Neutrality plots indicated that natural selection is the major influencing factor of codon usage bias, and that the impact of mutation pressure is comparatively minor. The methods for estimating host imposed translation pressure suggested that the polymerase acidic (PA) gene seems to be under less translational pressure compared to polymerase basic 1 (PB1) and polymerase basic 2 (PB2) genes. The multivariate statistical analysis of polymerase genes divided EIVs into four evolutionary diverged clusters - Pre-divergent, Eurasian, Florida sub-lineage 1 and 2. Various lineage specific amino acid substitutions observed in all polymerase genes of EIVs and especially, clade 2 EIVs underwent major variations which led to the emergence of a phylogenetically distinct group of EIVs originating from Richmond/1/07. The codon usage bias was low in all the polymerase genes of EIVs that was influenced by the multiple factors such as the nucleotide compositions, mutation pressure, aromaticity and hydropathicity. However, natural selection was the major influencing factor in defining the

  11. Finite Optimal Stopping Problems: The Seller's Perspective

    Science.gov (United States)

    Hemmati, Mehdi; Smith, J. Cole

    2011-01-01

    We consider a version of an optimal stopping problem, in which a customer is presented with a finite set of items, one by one. The customer is aware of the number of items in the finite set and the minimum and maximum possible value of each item, and must purchase exactly one item. When an item is presented to the customer, she or he observes its…

  12. Electron mass stopping power in H2

    Science.gov (United States)

    Fursa, Dmitry V.; Zammit, Mark C.; Threlfall, Robert L.; Savage, Jeremy S.; Bray, Igor

    2017-08-01

    Calculations of electron mass stopping power (SP) of electrons in H2 have been performed using the convergent close-coupling method for incident electron energies up to 2000 eV. Convergence of the calculated SP has been established by increasing the size of the close-coupling expansion from 9 to 491 states. Good agreement was found with the SP measurements of Munoz et al. [Chem. Phys. Lett. 433, 253 (2007), 10.1016/j.cplett.2006.10.114].

  13. The TRIUMF stopped π-μ channel

    International Nuclear Information System (INIS)

    Al-Qazzaz, N.M.M.; Beer, G.A.; Mason, G.R.

    1980-01-01

    The TRIUMF π-μ channel (M9) is described and the measured optical paramters are compared with design values. Measured beam characteristics of pions and muons for several different momenta are reported for protons incident on Be and Cu production targets. A beam of cloud muons at the channel momentum, from π decays near the production target, has been obtained having a high stopping density and small spot size. (auth)

  14. Relativistic theory of stopping for heavy ions

    International Nuclear Information System (INIS)

    Lindhard, J.; So/rensen, A.H.

    1996-01-01

    We calculate the electronic stopping power and the corresponding straggling for ions of arbitrary charge number, penetrating matter at any relativistic energy. The stopping powers are calculated by a simple method. Its starting point is the deviation of the precise theory from first-order quantum perturbation. We show that this deviation can be expressed in terms of the transport cross section, σ tr , for scattering of a free electron by the ion. In the nonrelativistic case the deviation is precisely the Bloch correction to Bethe close-quote s formula; we look into the nonrelativistic case in order to clarify both some features of our method and a seeming paradox in Rutherford scattering. The corresponding relativistic correction is obtained from σ tr for scattering of a Dirac electron in the ion potential. Here, the major practical advantage of the method shows up; we need not find the scattering distribution, but merely a single quantity, σ tr , determined by differences of successive phase shifts. For a point nucleus our results improve and extend those of Ahlen. Our final results, however, are based on atomic nuclei with standard radii. Thereby, the stopping is changed substantially already for moderate values of γ=(1-v 2 /c 2 ) -1/2 . An asymptotic saturation in stopping is obtained. Because of finite nuclear size, recoil corrections remain negligible at all energies. The average square fluctuation in energy loss is calculated as a simple fluctuation cross section for a free electron. The fluctuation in the relativistic case is generally larger than that of the perturbation formula, by a factor of ∼2 endash 3 for heavy ions. But the finite nuclear radius leads to a strong reduction at high energies and the elimination of the factor γ 2 belonging to point nuclei. copyright 1996 The American Physical Society

  15. Spectroscopy of hypernuclei with stopped kaons

    International Nuclear Information System (INIS)

    Tamura, H.; Brueckner, W.; Doebbeling, H.

    1987-09-01

    Pion momentum spectra from K - absorption at rest on various nuclear targets were measured by means of a magnetic spectrometer with wide momentum range (100 ∼ 300 MeV/c). The ground state of Σ - hypernucleus, if well bound with a narrow width, is expected to be populated in 12 C(stopped K - , π + ) inclusive (untagged) spectrum, but such a peak was not observed. The spectrum is compared with the DWIA calculations by Morimatsu and Yazaki, indicating that the depth of the nuclear potential of Σ - is shallower than 12 MeV, and that its imaginary part is larger than 5 MeV if the potential depth is about 10 MeV. In the 12 C(stopped K - , π - ) spectrum, the ground state ((p3/2) n -1 (s1/2) Λ ) and the excited states ((p3/2) n -1 (p) Λ ) of Λ 12 C were observed, and their formation probabilities were roughly in agreement with the results of DWIA calculations. In the π - spectra on 12 C, 9 Be, and 7 Li targets a distinct peak was observed at 132.1 ± 0.7 MeV/c. It is ascribed to π - from the mesic decay of Λ 4 H; Λ 4 H → 4 He π - . The formation probability of Λ 4 H on C, Be, or Li target is much larger than those of the discrete states of Λ 12 C via the direct (stopped K - , π - ) reaction. (author)

  16. Help Stop the Flu | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... page please turn Javascript on. Feature: Flu Shot Help Stop the Flu Past Issues / Winter 2011 Table ... CDC recommends that Americans do the following to help stop the flu: Cover nose and mouth with ...

  17. CDC Vital Signs: New Hope for Stopping HIV

    Science.gov (United States)

    ... 27 MB] Read the MMWR Science Clips New Hope for Stopping HIV Testing and Medical Care Save ... acquired immunodeficiency syndrome) and early death. There's new hope today for stopping HIV in the US. Medicines ( ...

  18. Optimal Stopping and Policyholder Behaviour in Life Insurance

    DEFF Research Database (Denmark)

    Gad, Kamille Sofie Tågholt

    . Below, I give a brief overview of the results of each of the chapters. A more thorough overview is presented in Chapter 1. In Chapter 2 we consider a general geometric Lévy process and solve the non-linear optimal stopping problem of maximizing the variance at the stopping time. For solving this problem...... we solve an auxiliary quadratic optimal stopping problem. We show that the solution to maximizing variance depends on whether randomized stopping times are included in the set of stopping times we maximize over. For some problems the inclusion of randomized stopping times increase the value function...... and for some it does not. Even when the value function is not affected by inclusion of randomized stopping times, a solution may be easier to identify when they are. In Chapter 3 we consider the non-linear optimal stopping problem of maximizing the mean minus a positive constant times the variance...

  19. Tail-extension following the termination codon is critical for release of the nascent chain from membrane-bound ribosomes in a reticulocyte lysate cell-free system.

    Science.gov (United States)

    Takahara, Michiyo; Sakaue, Haruka; Onishi, Yukiko; Yamagishi, Marifu; Kida, Yuichiro; Sakaguchi, Masao

    2013-01-11

    Nascent chain release from membrane-bound ribosomes by the termination codon was investigated using a cell-free translation system from rabbit supplemented with rough microsomal membrane vesicles. Chain release was extremely slow when mRNA ended with only the termination codon. Tail extension after the termination codon enhanced the release of the nascent chain. Release reached plateau levels with tail extension of 10 bases. This requirement was observed with all termination codons: TAA, TGA and TAG. Rapid release was also achieved by puromycin even in the absence of the extension. Efficient translation termination cannot be achieved in the presence of only a termination codon on the mRNA. Tail extension might be required for correct positioning of the termination codon in the ribosome and/or efficient recognition by release factors. Copyright © 2012. Published by Elsevier Inc.

  20. Intelligent Bus Stops in the Flexible Bus Systems

    OpenAIRE

    Razi Iqbal; Muhammad Usman Ghani

    2014-01-01

    The purpose of this paper is to discuss Intelligent Bus Stops in a special Demand Responsive Transit (DRT), the Flexible Bus System. These Intelligent Bus Stops are more efficient and information rich than Traditional Bus Stops. The real time synchronization of the Flexible Bus System makes it unique as compared to Traditional Bus Systems. The Main concern is to make Bus Stops intelligent and information rich. Buses are informed about the no. of passengers waiting at the upcoming ...

  1. Comprehensive analysis of the codon usage patterns in the envelope glycoprotein E2 gene of the classical swine fever virus.

    Directory of Open Access Journals (Sweden)

    Ye Chen

    Full Text Available The classical swine fever virus (CSFV, circulating worldwide, is a highly contagious virus. Since the emergence of CSFV, it has caused great economic loss in swine industry. The envelope glycoprotein E2 gene of the CSFV is an immunoprotective antigen that induces the immune system to produce neutralizing antibodies. Therefore, it is essential to study the codon usage of the E2 gene of the CSFV. In this study, 140 coding sequences of the E2 gene were analyzed. The value of effective number of codons (ENC showed low codon usage bias in the E2 gene. Our study showed that codon usage could be described mainly by mutation pressure ENC plot analysis combined with principal component analysis (PCA and translational selection-correlation analysis between the general average hydropathicity (Gravy and aromaticity (Aroma, and nucleotides at the third position of codons (A3s, T3s, G3s, C3s and GC3s. Furthermore, the neutrality analysis, which explained the relationship between GC12s and GC3s, revealed that natural selection had a key role compared with mutational bias during the evolution of the E2 gene. These results lay a foundation for further research on the molecular evolution of CSFV.

  2. Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

    Science.gov (United States)

    Aragonès, Lluís; Guix, Susana; Ribes, Enric; Bosch, Albert; Pintó, Rosa M

    2010-03-05

    Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

  3. Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

    Directory of Open Access Journals (Sweden)

    Lluís Aragonès

    2010-03-01

    Full Text Available Hepatitis A virus (HAV, the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

  4. Start-Stop Test Procedures on the PEMFC Stack Level

    DEFF Research Database (Denmark)

    Mitzel, Jens; Nygaard, Frederik; Veltzé, Sune

    The test is addressed to investigate the influence on stack durability of a long stop followed by a restart of a stack. Long stop should be defined as a stop in which the anodic compartment is fully filled by air due to stack leakages. In systems, leakage level of the stack is low and time to fil...

  5. Biobjective Optimization and Evaluation for Transit Signal Priority Strategies at Bus Stop-to-Stop Segment

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-01-01

    Full Text Available This paper proposes a new optimization framework for the transit signal priority strategies in terms of green extension, red truncation, and phase insertion at the stop-to-stop segment of bus lines. The optimization objective is to minimize both passenger delay and the deviation from bus schedule simultaneously. The objective functions are defined with respect to the segment between bus stops, which can include the adjacent signalized intersections and downstream bus stops. The transit priority signal timing is optimized by using a biobjective optimization framework considering both the total delay at a segment and the delay deviation from the arrival schedules at bus stops. The proposed framework is evaluated using a VISSIM model calibrated with field traffic volume and traffic signal data of Caochangmen Boulevard in Nanjing, China. The optimized TSP-based phasing plans result in the reduced delay and improved reliability, compared with the non-TSP scenario under the different traffic flow conditions in the morning peak hour. The evaluation results indicate the promising performance of the proposed optimization framework in reducing the passenger delay and improving the bus schedule adherence for the urban transit system.

  6. [Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

    Science.gov (United States)

    Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

    2009-06-01

    To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

  7. Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11.

    Science.gov (United States)

    Li, Manqing; Kao, Elaine; Gao, Xia; Sandig, Hilary; Limmer, Kirsten; Pavon-Eternod, Mariana; Jones, Thomas E; Landry, Sebastien; Pan, Tao; Weitzman, Matthew D; David, Michael

    2012-11-01

    In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway. However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.

  8. Production of β-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

    Science.gov (United States)

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

    2013-01-01

    In several types of thalassemia (including β039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying β-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the β039- thalassemia globin gene under control of the β-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of β-globin by K562 cell clones expressing the β039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from β039-thalassemia patients were demonstrated to be able to produce β-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of β0-thalassemia caused by stop codon mutations. PMID:19810011

  9. Stop feeling: inhibition of emotional interference following stop-signal trials.

    Science.gov (United States)

    Kalanthroff, Eyal; Cohen, Noga; Henik, Avishai

    2013-01-01

    Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop-signal reaction time (SSRT)] following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

  10. Stop feeling: Inhibition of emotional interference following stop-signal trials

    Directory of Open Access Journals (Sweden)

    Eyal eKalanthroff

    2013-03-01

    Full Text Available Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control (longer stop-signal reaction time following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

  11. Stopping-power ratios for dosimetry

    International Nuclear Information System (INIS)

    Andreo, P.

    1988-01-01

    The determination of the absorbed dose at a specified location in a medium irradiated with an electron or photon beam normally consists of two steps: (1) the determination of the mean absorbed dose to a detector by using a calibration factor or performing an absolute measurement, (2) the determination of the absorbed dose to the medium at the point of interest by calculations based on the knowledge of the absorbed dose to the detector and the different stopping and scattering properties of the medium and the detector material. When the influence of the detector is so small that the electron fluence in the medium is not modified, the ratio of the mass collision stopping power of the two materials accounts for the differences in energy deposition, and provides a conversion factor to relate the absorbed dose in both materials. Today, all national and international dosimetry protocols and codes of practice are based on such procedures, and the user easily can carry out these steps using tabulated data to convert a measured quantity to absorbed dose in the irradiated medium at the location of interest. Effects due to the spatial extension of the detector are taken into account using perturbation correction factors. The Monte Carlo method has become the most common and powerful calculational technique for determining the electron fluence (energy spectra) under different irradiation conditions. Cavity theory is then used to calculate stopping-power ratios. In this chapter, the different steps needed to evaluate s-ratios will be considered, emphasizing the different types of cavity-theory integrals and the Monte Carlo techniques used to derive the necessary electron spectra in the range of energies commonly used in radiation dosimetry, i.e., photon and electron beams with energies up to 50 MeV

  12. End-Stop Exemplar Based Recognition

    DEFF Research Database (Denmark)

    Olsen, Søren I.

    2003-01-01

    An approach to exemplar based recognition of visual shapes is presented. The shape information is described by attributed interest points (keys) detected by an end-stop operator. The attributes describe the statistics of lines and edges local to the interest point, the position of neighboring int...... interest points, and (in the training phase) a list of recognition names. Recognition is made by a simple voting procedure. Preliminary experiments indicate that the recognition is robust to noise, small deformations, background clutter and partial occlusion....

  13. Jojoba could stop the desert creep

    Energy Technology Data Exchange (ETDEWEB)

    1982-03-25

    The Sahara desert is estimated to be expanding at a rate of 5km a year. The Sudanese government is experimenting with jojoba in six different regions as the bush has the potential to stop this ''desert creep''. The plant, a native to Mexico, is long known for its resistance to drought and for the versatile liquid wax that can be extracted from its seeds. It is estimated that one hectare of mature plants could produce 3000 kg of oil, currently selling at $50 per litre, and so earn valuable foreign currency.

  14. Early Stop Criterion from the Bootstrap Ensemble

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Larsen, Jan; Fog, Torben L.

    1997-01-01

    This paper addresses the problem of generalization error estimation in neural networks. A new early stop criterion based on a Bootstrap estimate of the generalization error is suggested. The estimate does not require the network to be trained to the minimum of the cost function, as required...... by other methods based on asymptotic theory. Moreover, in contrast to methods based on cross-validation which require data left out for testing, and thus biasing the estimate, the Bootstrap technique does not have this disadvantage. The potential of the suggested technique is demonstrated on various time...

  15. Frame by frame stop motion non-traditional approaches to stop motion animation

    CERN Document Server

    Gasek, Tom

    2011-01-01

    In a world that is dominated by computer images, alternative stop motion techniques like pixilation, time-lapse photography and down-shooting techniques combined with new technologies offer a new, tangible and exciting approach to animation. With over 25 years professional experience, industry veteran, Tom Gasek presents a comprehensive guide to stop motion animation without the focus on puppetry or model animation. With tips, tricks and hands-on exercises, Frame by Frame will help both experienced and novice filmmakers get the most effective results from this underutilized branch of animation

  16. Three types of preS1 start codon deletion variants in the natural course of chronic hepatitis B infection.

    Science.gov (United States)

    Choe, Won Hyeok; Kim, Hong; Lee, So-Young; Choi, Yu-Min; Kwon, So Young; Moon, Hee Won; Hur, Mina; Kim, Bum-Joon

    2017-12-12

    Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P start codon deletion variants changes according to the immune phases of CHB infection, and each variant type is associated with different clinical parameters. PreS1 start codon deletion variants might interact with the host immune response differently according to their variant types. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Combination of the Endogenous lhcsr1 Promoter and Codon Usage Optimization Boosts Protein Expression in the Moss Physcomitrella patens

    Directory of Open Access Journals (Sweden)

    Manuel Hiss

    2017-10-01

    Full Text Available The moss Physcomitrella patens is used both as an evo-devo model and biotechnological production system for metabolites and pharmaceuticals. Strong in vivo expression of genes of interest is important for production of recombinant proteins, e.g., selectable markers, fluorescent proteins, or enzymes. In this regard, the choice of the promoter sequence as well as codon usage optimization are two important inside factors to consider in order to obtain optimum protein accumulation level. To reliably quantify fluorescence, we transfected protoplasts with promoter:GFP fusion constructs and measured fluorescence intensity of living protoplasts in a plate reader system. We used the red fluorescent protein mCherry under 2x 35S promoter control as second reporter to normalize for different transfection efficiencies. We derived a novel endogenous promoter and compared deletion variants with exogenous promoters. We used different codon-adapted green fluorescent protein (GFP genes to evaluate the influence of promoter choice and codon optimization on protein accumulation in P. patens, and show that the promoter of the gene of P. patens chlorophyll a/b binding protein lhcsr1 drives expression of GFP in protoplasts significantly (more than twofold better than the commonly used 2x 35S promoter or the rice actin1 promoter. We identified a shortened 677 bp version of the lhcsr1 promoter that retains full activity in protoplasts. The codon optimized GFP yields significantly (more than twofold stronger fluorescence signals and thus demonstrates that adjusting codon usage in P. patens can increase expression strength. In combination, new promotor and codon optimized GFP conveyed sixfold increased fluorescence signal.

  18. Elevation of the Yields of Very Long Chain Polyunsaturated Fatty Acids via Minimal Codon Optimization of Two Key Biosynthetic Enzymes.

    Directory of Open Access Journals (Sweden)

    Fei Xia

    Full Text Available Eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17 and Docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19 are nutritionally beneficial to human health. Transgenic production of EPA and DHA in oilseed crops by transferring genes originating from lower eukaryotes, such as microalgae and fungi, has been attempted in recent years. However, the low yield of EPA and DHA produced in these transgenic crops is a major hurdle for the commercialization of these transgenics. Many factors can negatively affect transgene expression, leading to a low level of converted fatty acid products. Among these the codon bias between the transgene donor and the host crop is one of the major contributing factors. Therefore, we carried out codon optimization of a fatty acid delta-6 desaturase gene PinD6 from the fungus Phytophthora infestans, and a delta-9 elongase gene, IgASE1 from the microalga Isochrysis galbana for expression in Saccharomyces cerevisiae and Arabidopsis respectively. These are the two key genes encoding enzymes for driving the first catalytic steps in the Δ6 desaturation/Δ6 elongation and the Δ9 elongation/Δ8 desaturation pathways for EPA/DHA biosynthesis. Hence expression levels of these two genes are important in determining the final yield of EPA/DHA. Via PCR-based mutagenesis we optimized the least preferred codons within the first 16 codons at their N-termini, as well as the most biased CGC codons (coding for arginine within the entire sequences of both genes. An expression study showed that transgenic Arabidopsis plants harbouring the codon-optimized IgASE1 contained 64% more elongated fatty acid products than plants expressing the native IgASE1 sequence, whilst Saccharomyces cerevisiae expressing the codon optimized PinD6 yielded 20 times more desaturated products than yeast expressing wild-type (WT PinD6. Thus the codon optimization strategy we developed here offers a simple, effective and low-cost alternative to whole gene synthesis for high

  19. Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA.

    Science.gov (United States)

    Ma, X X; Feng, Y P; Gu, Y X; Zhou, J H; Ma, Z R

    2016-06-01

    As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA.

  20. Enhanced phosphoserine insertion during Escherichia coli protein synthesis via partial UAG codon reassignment and release factor 1 deletion

    Science.gov (United States)

    Heinemann, Ilka U.; Rovner, Alexis J.; Aerni, Hans R.; Rogulina, Svetlana; Cheng, Laura; Olds, William; Fischer, Jonathan T.; Söll, Dieter; Isaacs, Farren J.; Rinehart, Jesse

    2012-01-01

    Genetically encoded phosphoserine incorporation programmed by the UAG codon was achieved by addition of engineered elongation factor and an archaeal aminoacyl-tRNA synthetase to the normal Escherichia coli translation machinery (Park (2011) Science 333, 1151). However, protein yield suffers from expression of the orthogonal phosphoserine translation system and competition with release factor 1 (RF-1). In a strain lacking RF-1, phosphoserine phosphatase, and where 7 UAG codons residing in essential genes were converted to UAA, phosphoserine incorporation into GFP and WNK4 was significantly elevated, but with an accompanying loss in cellular fitness and viability. PMID:22982858

  1. Stop-gain mutations in PKP2 are associated with a later age of onset of arrhythmogenic right ventricular cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Mireia Alcalde

    Full Text Available BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC is a cardiac disease characterized by the presence of fibrofatty replacement of the right ventricular myocardium, which may cause ventricular arrhythmias and sudden cardiac death. Pathogenic mutations in several genes encoding mainly desmosomal proteins have been reported. Our aim is to perform genotype-phenotype correlations to establish the diagnostic value of genetics and to assess the role of mutation type in age-related penetrance in ARVC. METHODS AND RESULTS: Thirty unrelated Spanish patients underwent a complete clinical evaluation. They all were screened for PKP2, DSG2, DSC2, DSP, JUP and TMEM43 genes. A total of 70 relatives of four families were also studied. The 30 patients fulfilled definite disease diagnostic criteria. Genetic analysis revealed a pathogenic mutation in 19 patients (13 in PKP2, 3 in DSG2, 2 in DSP, and 1 in DSC2. Nine of these mutations created a truncated protein due to the generation of a stop codon. Familial assessment revealed 28 genetic carriers among family members. Stop-gain mutations were associated to a later age of onset of ARVC, without differences in the severity of the pathology. CONCLUSIONS: Familial genetic analysis helps to identify the cause responsible for the pathology. In discrepancy with previous studies, the presence of a truncating protein does not confer a worse severity. This information could suggest that truncating proteins may be compensated by the normal allele and that missense mutations may act as poison peptides.

  2. Interaction between two stopped light pulses

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi-Hsin, E-mail: yhchen920@gmail.com; Lee, Meng-Jung, E-mail: yhchen920@gmail.com; Hung, Weilun, E-mail: yhchen920@gmail.com; Yu, Ite A., E-mail: yu@phys.nthu.edu.tw [Department of Physics and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chen, Ying-Cheng [Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan and Department of Physics and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chen, Yong-Fan [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China)

    2014-03-05

    The efficiency of a nonlinear optical process is proportional to the interaction time. We report a scheme of all-optical switching based on two motionless light pulses via the effect of electromagnetically induced transparency. One pulse was stopped as the stationary light pulse (SLP) and the other was stopped as stored light. The time of their interaction via the medium can be prolonged and, hence, the optical nonlinearity is greatly enhanced. Using a large optical density (OD) of 190, we achieved a very long interaction time of 6.9 μs. This can be analogous to the scheme of trapping light pulses by an optical cavity with a Q factor of 8×10{sup 9}. With the approach of using moving light pulses in the best situation, a switch can only be activated at 2 photons per atomic absorption cross section. With the approach of employing a SLP and a stored light pulse, a switch at only 0.56 photons was achieved and the efficiency is significantly improved. Moreover, the simulation results are in good agreement with the experimental data and show that the efficiency can be further improved by increasing the OD of the medium. Our work advances the technology in quantum information manipulation utilizing photons.

  3. Seismic stops vs. snubbers, a reliable alternative

    International Nuclear Information System (INIS)

    Cloud, R.L.; Anderson, P.H.; Leung, J.S.M.

    1988-01-01

    The Seismic Stops methodology has been developed to provide a reliable alternative for providing seismic support to nuclear power plant piping. The concept is based on using rigid passive supports with large clearances. These gaps permit unrestrained thermal expansion while limiting excessive seismic displacements. This type of restraint has performed successfully in fossil fueled power plants. A simplified production analysis tool has been developed which evaluates the nonlinear piping response including the effect of the gapped supports. The methodology utilizes the response spectrum approach and has been incorporated into a piping analysis computer program RLCA-GAP. Full scale shake table tests of piping specimens were performed to provide test correlation with the developed methodology. Analyses using RLCA-GAP were in good agreement with test results. A sample piping system was evaluated using the Seismic Stops methodology to replace the existing snubbers with passive gapped supports. To provide further correlation data, the sample system was also evaluated using nonlinear time history analysis. The correlation comparisons showed RLCA-GAP to be a viable methodology and a reliable alternative for snubber optimization and elimination. (orig.)

  4. Contrast effects on stop consonant identification.

    Science.gov (United States)

    Diehl, R L; Elman, J L; McCusker, S B

    1978-11-01

    Changes in the identification of speech sounds following selective adaptation are usually attributed to a reduction in sensitivity of auditory feature detectors. An alternative explanation of these effects is based on the notion of response contrast. In several experiments, subjects identified the initial segment of synthetic consonant-vowel syllables as either the voiced stop [b] or the voiceless stop [ph]. Each test syllable had a value of voice onset time (VOT) that placed it near the English voiced-voiceless boundary. When the test syllables were preceded by a single clear [b] (VOT = -100 msec), subjects tended to identify them as [ph], whereas when they were preceded by an unambiguous [ph] (VOT = 100 msec), the syllables were predominantly labeled [b]. This contrast effect occurred even when the contextual stimuli were velar and the test stimuli were bilabial, which suggests a featural rather than a phonemic basis for the effect. To discount the possibility that these might be instances of single-trial sensory adaptation, we conducted a similar experiment in which the contextual stimuli followed the test items. Reliable contrast effects were still obtained. In view of these results, it appears likely that response contrast accounts for at least some component of the adaptation effects reported in the literature.

  5. Interaction between two stopped light pulses

    International Nuclear Information System (INIS)

    Chen, Yi-Hsin; Lee, Meng-Jung; Hung, Weilun; Yu, Ite A.; Chen, Ying-Cheng; Chen, Yong-Fan

    2014-01-01

    The efficiency of a nonlinear optical process is proportional to the interaction time. We report a scheme of all-optical switching based on two motionless light pulses via the effect of electromagnetically induced transparency. One pulse was stopped as the stationary light pulse (SLP) and the other was stopped as stored light. The time of their interaction via the medium can be prolonged and, hence, the optical nonlinearity is greatly enhanced. Using a large optical density (OD) of 190, we achieved a very long interaction time of 6.9 μs. This can be analogous to the scheme of trapping light pulses by an optical cavity with a Q factor of 8×10 9 . With the approach of using moving light pulses in the best situation, a switch can only be activated at 2 photons per atomic absorption cross section. With the approach of employing a SLP and a stored light pulse, a switch at only 0.56 photons was achieved and the efficiency is significantly improved. Moreover, the simulation results are in good agreement with the experimental data and show that the efficiency can be further improved by increasing the OD of the medium. Our work advances the technology in quantum information manipulation utilizing photons

  6. Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming of human adult fibroblasts.

    Science.gov (United States)

    Diecke, Sebastian; Lisowski, Leszek; Kooreman, Nigel G; Wu, Joseph C

    2014-01-01

    The ability to induce pluripotency in somatic cells is one of the most important scientific achievements in the fields of stem cell research and regenerative medicine. This technique allows researchers to obtain pluripotent stem cells without the controversial use of embryos, providing a novel and powerful tool for disease modeling and drug screening approaches. However, using viruses for the delivery of reprogramming genes and transcription factors may result in integration into the host genome and cause random mutations within the target cell, thus limiting the use of these cells for downstream applications. To overcome this limitation, various non-integrating techniques, including Sendai virus, mRNA, minicircle, and plasmid-based methods, have recently been developed. Utilizing a newly developed codon optimized 4-in-1 minicircle (CoMiC), we were able to reprogram human adult fibroblasts using chemically defined media and without the need for feeder cells.

  7. CodonTest: modeling amino acid substitution preferences in coding sequences.

    Directory of Open Access Journals (Sweden)

    Wayne Delport

    2010-08-01

    Full Text Available Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models. However, these approaches have been limited by the necessity for large alignments in their estimation. An alternative approach is to assume that substitution rates between amino acid pairs can be subdivided into rate classes, dependent on the information content of the alignment. However, given the combinatorially large number of such models, an efficient model search strategy is needed. Here we develop a Genetic Algorithm (GA method for the estimation of such models. A GA is used to assign amino acid substitution pairs to a series of rate classes, where is estimated from the alignment. Other parameters of the phylogenetic Markov model, including substitution rates, character frequencies and branch lengths are estimated using standard maximum likelihood optimization procedures. We apply the GA to empirical alignments and show improved model fit over existing models of codon evolution. Our results suggest that current models are poor approximations of protein evolution and thus gene and organism specific multi-rate models that incorporate amino acid substitution biases are preferred. We further anticipate that the clustering of amino acid substitution rates into classes will be biologically informative, such that genes with similar functions exhibit similar clustering, and hence this clustering will be useful for the evolutionary fingerprinting of genes.

  8. Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias.

    Science.gov (United States)

    Esposito, Lauren A; Gupta, Swati; Streiter, Fraida; Prasad, Ashley; Dennehy, John J

    2016-10-01

    In an genomics course sponsored by the Howard Hughes Medical Institute (HHMI), undergraduate students have isolated and sequenced the genomes of more than 1,150 mycobacteriophages, creating the largest database of sequenced bacteriophages able to infect a single host, Mycobacterium smegmatis , a soil bacterium. Genomic analysis indicates that these mycobacteriophages can be grouped into 26 clusters based on genetic similarity. These clusters span a continuum of genetic diversity, with extensive genomic mosaicism among phages in different clusters. However, little is known regarding the primary hosts of these mycobacteriophages in their natural habitats, nor of their broader host ranges. As such, it is possible that the primary host of many newly isolated mycobacteriophages is not M. smegmatis , but instead a range of closely related bacterial species. However, determining mycobacteriophage host range presents difficulties associated with mycobacterial cultivability, pathogenicity and growth. Another way to gain insight into mycobacteriophage host range and ecology is through bioinformatic analysis of their genomic sequences. To this end, we examined the correlations between the codon usage biases of 199 different mycobacteriophages and those of several fully sequenced mycobacterial species in order to gain insight into the natural host range of these mycobacteriophages. We find that UPGMA clustering tends to match, but not consistently, clustering by shared nucleotide sequence identify. In addition, analysis of GC content, tRNA usage and correlations between mycobacteriophage and mycobacterial codon usage bias suggests that the preferred host of many clustered mycobacteriophages is not M. smegmatis but other, as yet unknown, members of the mycobacteria complex or closely allied bacterial species.

  9. Detecting consistent patterns of directional adaptation using differential selection codon models.

    Science.gov (United States)

    Parto, Sahar; Lartillot, Nicolas

    2017-06-23

    Phylogenetic codon models are often used to characterize the selective regimes acting on protein-coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by modeling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions. Here, we introduce a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles. Our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.

  10. Stopping power for heavy ions in low energy region

    International Nuclear Information System (INIS)

    Kitagawa, Mitsuo

    1983-01-01

    Review is made for the study on the power for stopping heavy ions. The studies on the power for stopping heavy ions passing through materials have been developed in the last twenty years due to the accuracy improvement in the data analysis of the power for stopping light ions, the requirement of data establishment on the power for stopping heavy ions from fusion research and the development of the experimental studies by heavy-ion accelerators. The relation between the analysis of the power for stopping heavy ions and the power for stopping light ions is described from the standpoint that the results on the power for stopping light ions serve as the guide for the study on the power for stopping heavy ions. Both at present and in future. The analysis of stopping power data with the accuracy from +-10 to 20 % is possible from the theoretical analysis of effective electric charge and its systematic table of the numerical data. The outline of the scaling rule on effective electric charge is discussed. The deviation of the experimental data from the scaling rule is discussed by comparing with the measured values of effective electric charge ratio. Various analyses of the power for stopping heavy ions are summarized. (Asami, T.)

  11. Intelligent Bus Stops in the Flexible Bus Systems

    Directory of Open Access Journals (Sweden)

    Razi Iqbal

    2014-09-01

    Full Text Available The purpose of this paper is to discuss Intelligent Bus Stops in a special Demand Responsive Transit (DRT, the Flexible Bus System. These Intelligent Bus Stops are more efficient and information rich than Traditional Bus Stops. The real time synchronization of the Flexible Bus System makes it unique as compared to Traditional Bus Systems. The Main concern is to make Bus Stops intelligent and information rich. Buses are informed about the no. of passengers waiting at the upcoming Bus Stops. If there are no passengers to ride or get off on upcoming Bus Stop, the Bus can skip that Bus Stop and head towards the next Bus Stop where passenger is waiting, which will decrease the ride time of the passengers on the Bus and also the wait time of the passengers waiting on the upcoming Bus Stops. Providing more information at Bus Stops about the Destination (Time to Destination, Distance to Destination etc. and Buses (Bus Location, Arrival Time of Bus etc. makes it easier for the passengers to decide whether to ride a particular Bus or not.

  12. Large scale comparative codon-pair context analysis unveils general rules that fine-tune evolution of mRNA primary structure.

    Directory of Open Access Journals (Sweden)

    Gabriela Moura

    Full Text Available BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

  13. Remune trial will stop; new trials planned.

    Science.gov (United States)

    James, J S

    1999-05-21

    A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

  14. Stop Lepton Associated Production at Hadron Colliders

    CERN Document Server

    Alves, A; Plehn, Tilman

    2003-01-01

    At hadron colliders, the search for R-parity violating supersymmetry can probe scalar masses beyond what is covered by pair production processes. We evaluate the next-to-leading order SUSY-QCD corrections to the associated stop or sbottom production with a lepton through R-parity violating interactions. We show that higher order corrections render the theoretical predictions more stable with respect to variations of the renormalization and factorization scales and that the total cross section is enhanced by a factor up to 70% at the Tevatron and 50% at the LHC. We investigate in detail how the heavy supersymmetric states decouple from the next-to-leading order process, which gives rise to a theory with an additional scalar leptoquark. In this scenario the inclusion of higher order QCD corrections increases the Tevatron reach on leptoquark masses by up to 40 GeV and the LHC reach by up to 200 GeV.

  15. The Novel Microwave Stop-Band Filter

    Directory of Open Access Journals (Sweden)

    R. E. Chernobrovkin

    2008-01-01

    Full Text Available The stop-band filter with the new band-rejection element is proposed. The element is a coaxial waveguide with the slot in the centre conductor. In the frame of this research, the numerical and experimental investigations of the amplitude-frequency characteristics of the filter are carried out. It is noted that according to the slot parameters the two typical resonances (half-wave and quarter-wave can be excited. The rejection band of the single element is defined by the width, depth, and dielectric filling of the slot. Fifth-order Chebyshev filter utilizing the aforementioned element is also synthesized, manufactured, and tested. The measured and simulated results are in good agreement. The experimental filter prototype exhibits the rejection band 0.86 GHz at the level −40 dB.

  16. 10 blows that stopped nuclear power

    International Nuclear Information System (INIS)

    Komanoff, C.

    1991-01-01

    The author describes these 10 blows in chronological order, 1973 through 1981, namely: (1) Arab Oil Embargo; (2) India Explodes a Bomb; (3) NRC replaces AEC; (4) Fire at Browns Ferry; (5) General Electric and NRC Engineers switch Sides; (6) Amory Lovins Recasts the Energy Debate; (7) The Seabrook Occupation; (8) The Three Mile Island Accident; (9) Federal Reserve Tightens the Money Supply; and (1) Pacific Gas and Electric Co. Gets it Backwards at Diablo Canyon. he stops there, not including the Washington Public Power Supply fiasco and the Chernobyl disaster, feeling nuclear expansion was essentially foreclosed without them. Further, he feels nuclear power seems fated to be forever at the mercy of forces beyond its control

  17. Comparative investigation of the various determinants that influence the codon and amino acid usage patterns in the genus Bifidobacterium.

    Science.gov (United States)

    Roy, Ayan; Mukhopadhyay, Subhasish; Sarkar, Indrani; Sen, Arnab

    2015-06-01

    Various strains of the genus Bifidobacterium are crucial members of the human, animal and insect gut, associated with beneficial probiotic activities. An extensive analysis on codon and amino acid usage of the GC rich genus Bifidobacterium has been executed in the present study. Multivariate statistical analysis revealed a coupled effect of GC compositional constraint and natural selection for translational efficiency to be operative in producing the observed codon usage variations. Gene expression level was inferred to be the most crucial factor governing the codon usage patterns. Amino acid usage was found to be influenced significantly by hydrophobic and aromatic character of the encoded proteins. Gene expressivity and protein energetic cost also had considerable impact on the differential mode of amino acid usage. The genus was found to strictly obey the cost-minimization hypothesis as was reflected from the amino acid usage patterns of the potential highly expressed gene products. Evolutionary analysis revealed that the highly expressed genes were candidates to extreme evolutionary selection pressure and indicated a high degree of conservation at the proteomic level. Interestingly, the complimentary strands of replication appeared to evolve under similar evolutionary constraints which might be addressed as a consequence of absence of replicational selection and lack of strand-specific asymmetry among the members of the genus. Thus, the present endeavor confers considerable know-how pertaining to the codon and amino acid usage intricacies in Bifidobacterium and might prove handy for further scientific investigations associated with the concerned domain.

  18. Association of the p53 codon 72 polymorphism to gastric cancer risk in a high risk population of Costa Rica

    International Nuclear Information System (INIS)

    Alpizar-Alpizar, Warner; Sierra, Rafaela; Cuenca, Patricia; Une, Clas; Mena, Fernando; Perez-Perez, Guillermo Ignacio

    2005-01-01

    Gastric cancer is the second most common cancer associated death cause worldwide. Several factors have been associated with higher risk to develop gastric cancer, among them genetic predisposition. The p53 gene has a polymorphism located at codon 72, which has been associated with higher risk of several types of cancer, including gastric cancer. The aim of this study was to determine the association of p53, codon 72 polymorphism, with the risk of gastric cancer and pre-malignant lesions in a high-risk population from Costa Rica. The genotyping was carried out by PCR-RFLP in a sample of 58 gastric cancer patients, 99 control persons and 41 individuals classified as group I and II, according to the Japanese histological classification. No association was found for p53, codon 72 polymorphism with neither the risk of gastric cancer nor the risk of less severe gastric lesions in the studied sample. Based on this study and taking into account other studies carried out with p53, codon 72 polymorphism, the role of this polymorphism in the development of gastric cancer remains unclear. De novo mutations on p53 gene produced during neoplastic development of this disease might play a greater role than germinal polymorphisms of this same gene. Other polymorphic genes have been associated with higher risk to develop gastric cancer. (author) [es

  19. Kissing loops hide premature termination codons in pre-mRNAof selenoprotein genes and in genes containing programmedribosomal frameshifts

    DEFF Research Database (Denmark)

    Knudsen, Steen; Brunak, Søren

    1997-01-01

    A novel RNA secondary structure that places the selenocysteine codon UGA in one hairpin and a donor splice site in another, has been discovered in selenoprotein genes. The presence of the structure resolves the discrepancy that the selenocysteine triplet, UGA, should block splicing. Without a spe...

  20. TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies

    NARCIS (Netherlands)

    Klug, Stefanie J.; Ressing, Meike; Koenig, Jochem; Abba, Martin C.; Agorastos, Theodoros; Brenna, Sylvia M. F.; Ciotti, Marco; Das, B. R.; Del Mistro, Annarosa; Dybikowska, Aleksandra; Giuliano, Anna R.; Gudleviciene, Zivile; Gyllensten, Ulf; Haws, Andrea L. F.; Helland, Aslaug; Herrington, C. Simon; Hildesheim, Alan; Humbey, Olivier; Jee, Sun H.; Kim, Jae Weon; Madeleine, Margaret M.; Menczer, Joseph; Ngan, Hextan Y. S.; Nishikawa, Akira; Niwa, Yoshimitsu; Pegoraro, Rosemary; Pillai, M. R.; Ranzani, Gulielmina; Rezza, Giovanni; Rosenthal, Adam N.; Roychoudhury, Susanta; Saranath, Dhananjaya; Schmitt, Virginia M.; Sengupta, Sharmila; Settheetham-Ishida, Wannapa; Shirasawa, Hiroshi; Snijders, Peter J. F.; Stoler, Mark H.; Suarez-Rincon, Angel E.; Szarka, Krisztina; Tachezy, Ruth; Ueda, Masatsugu; van der Zee, Ate G. J.; Doeberitz, Magnus von Knebel; Wu, Ming-Tsang; Yamashita, Tsuyoshi; Zehbe, Ingeborg; Blettner, Maria

    Background Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who

  1. Abortive translation caused by peptidyl-tRNA drop-off at NGG codons in the early coding region of mRNA

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2005-01-01

    In Escherichia coli the codons CGG, AGG, UGG or GGG (NGG codons) but not GGN or GNG (where N is non-G) are associated with low expression of a reporter gene, if located at positions +2 to +5. Induction of a lacZ reporter gene with any one of the NGG codons at position +2 to +5 does not influence......-type or the mutant strain. The inhibitory effect on the pth mutant strain by NGG codons at location +5 was suppressed by overexpression of the Pth enzyme from a plasmid. However, the overexpression of cognate tRNAs for AGG or GGG did not rescue from the growth inhibition associated with these codons early...

  2. 20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

    Science.gov (United States)

    2010-04-01

    ... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

  3. Design of permanent block stopping to resist strata convergence

    Energy Technology Data Exchange (ETDEWEB)

    Ray, R.E.

    1985-11-01

    Conventional concrete block plastered with a cementitious coating is the most common material used in the construction of permanent stoppings to direct airflow in underground mines in the US. All mines experience various degrees of strata convergence depending on depth of overburden, geological conditions, and type of roof support employed. Strata convergence will cause cracks and joint openings in masonry stoppings, resulting in significant air leakage losses. Where strata convergence is severe, complete structural failure of the stopping can ultimately occur. Reconstruction of damaged or destroyed stoppings adds expensive overheads to mining operations, and even greater expenses are incurred from the additional fan horsepower required to overcome leakage losses. Ideally, a stopping should maintain high resistance to airflow while yielding to strata convergence. By properly incorporating a polyisocyanurate rigid foam material within the masonry block structure, stopping service life can be increased in mines experiencing strata convergence problems such as floor heave, roof loading, and lateral rib movement.

  4. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    Science.gov (United States)

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  5. Stopping test of iterative methods for solving PDE

    International Nuclear Information System (INIS)

    Wang Bangrong

    1991-01-01

    In order to assure the accuracy of the numerical solution of the iterative method for solving PDE (partial differential equation), the stopping test is very important. If the coefficient matrix of the system of linear algebraic equations is strictly diagonal dominant or irreducible weakly diagonal dominant, the stopping test formulas of the iterative method for solving PDE is proposed. Several numerical examples are given to illustrate the applications of the stopping test formulas

  6. On poisson-stopped-sums that are mixed poisson

    OpenAIRE

    Valero Baya, Jordi; Pérez Casany, Marta; Ginebra Molins, Josep

    2013-01-01

    Maceda (1948) characterized the mixed Poisson distributions that are Poisson-stopped-sum distributions based on the mixing distribution. In an alternative characterization of the same set of distributions here the Poisson-stopped-sum distributions that are mixed Poisson distributions is proved to be the set of Poisson-stopped-sums of either a mixture of zero-truncated Poisson distributions or a zero-modification of it. Peer Reviewed

  7. Stopping power, its meaning, and its general characteristics

    International Nuclear Information System (INIS)

    Inokuti, Mitio.

    1995-01-01

    This essay presents remarks on the meaning of stopping, power and of its magnitude. More precisely, the first set of remarks concerns the connection of stopping power with elements of particle-transport theory, which describes particle transport and its consequences in full detail, including its stochastic aspects. The second set of remarks concerns the magnitude of the stopping power of a material and its relation with the material's electronic structure and other properties

  8. Reduce manual curation by combining gene predictions from multiple annotation engines, a case study of start codon prediction.

    Directory of Open Access Journals (Sweden)

    Thomas H A Ederveen

    Full Text Available Nowadays, prokaryotic genomes are sequenced faster than the capacity to manually curate gene annotations. Automated genome annotation engines provide users a straight-forward and complete solution for predicting ORF coordinates and function. For many labs, the use of AGEs is therefore essential to decrease the time necessary for annotating a given prokaryotic genome. However, it is not uncommon for AGEs to provide different and sometimes conflicting predictions. Combining multiple AGEs might allow for more accurate predictions. Here we analyzed the ab initio open reading frame (ORF calling performance of different AGEs based on curated genome annotations of eight strains from different bacterial species with GC% ranging from 35-52%. We present a case study which demonstrates a novel way of comparative genome annotation, using combinations of AGEs in a pre-defined order (or path to predict ORF start codons. The order of AGE combinations is from high to low specificity, where the specificity is based on the eight genome annotations. For each AGE combination we are able to derive a so-called projected confidence value, which is the average specificity of ORF start codon prediction based on the eight genomes. The projected confidence enables estimating likeliness of a correct prediction for a particular ORF start codon by a particular AGE combination, pinpointing ORFs notoriously difficult to predict start codons. We correctly predict start codons for 90.5±4.8% of the genes in a genome (based on the eight genomes with an accuracy of 81.1±7.6%. Our consensus-path methodology allows a marked improvement over majority voting (9.7±4.4% and with an optimal path ORF start prediction sensitivity is gained while maintaining a high specificity.

  9. Research of the stopping distance for different road conditions

    Directory of Open Access Journals (Sweden)

    Daniel LYUBENOV

    2011-01-01

    Full Text Available In this paper a modern method for determination of stopping distance is represented. Application of the non-contact VBOX 3i 100Hz GPS Data Logger speed and distance measurement system is represented. A description of the total stopping distance of vehicle main components - driver reaction time, vehicle reaction time and vehicle braking capability has been made. Research of the total stopping distance of a vehicle for different road conditions has been made. The results for the stopping distance can be very useful in the expert practice.

  10. The IAEA stopping power database, following the trends in stopping power of ions in matter

    Science.gov (United States)

    Montanari, C. C.; Dimitriou, P.

    2017-10-01

    The aim of this work is to present an overview of the state of art of the energy loss of ions in matter, based on the new developments in the stopping power database of the International Atomic Energy Agency (IAEA). This exhaustive collection of experimental data, graphs, programs and comparisons, is the legacy of Helmut Paul, who made it accessible to the global scientific community, and has been extensively employed in theoretical and experimental research during the last 25 years. The field of stopping power in matter is evolving, with new trends in materials of interest, including oxides, nitrides, polymers, and biological targets. Our goal is to identify areas of interest and emerging data needs to meet the requirements of a continuously developing user community.

  11. Simulated evolution applied to study the genetic code optimality using a model of codon reassignments.

    Science.gov (United States)

    Santos, José; Monteagudo, Angel

    2011-02-21

    As the canonical code is not universal, different theories about its origin and organization have appeared. The optimization or level of adaptation of the canonical genetic code was measured taking into account the harmful consequences resulting from point mutations leading to the replacement of one amino acid for another. There are two basic theories to measure the level of optimization: the statistical approach, which compares the canonical genetic code with many randomly generated alternative ones, and the engineering approach, which compares the canonical code with the best possible alternative. Here we used a genetic algorithm to search for better adapted hypothetical codes and as a method to guess the difficulty in finding such alternative codes, allowing to clearly situate the canonical code in the fitness landscape. This novel proposal of the use of evolutionary computing provides a new perspective in the open debate between the use of the statistical approach, which postulates that the genetic code conserves amino acid properties far better than expected from a random code, and the engineering approach, which tends to indicate that the canonical genetic code is still far from optimal. We used two models of hypothetical codes: one that reflects the known examples of codon reassignment and the model most used in the two approaches which reflects the current genetic code translation table. Although the standard code is far from a possible optimum considering both models, when the more realistic model of the codon reassignments was used, the evolutionary algorithm had more difficulty to overcome the efficiency of the canonical genetic code. Simulated evolution clearly reveals that the canonical genetic code is far from optimal regarding its optimization. Nevertheless, the efficiency of the canonical code increases when mistranslations are taken into account with the two models, as indicated by the fact that the best possible codes show the patterns of the

  12. Simulated evolution applied to study the genetic code optimality using a model of codon reassignments

    Directory of Open Access Journals (Sweden)

    Monteagudo Ángel

    2011-02-01

    Full Text Available Abstract Background As the canonical code is not universal, different theories about its origin and organization have appeared. The optimization or level of adaptation of the canonical genetic code was measured taking into account the harmful consequences resulting from point mutations leading to the replacement of one amino acid for another. There are two basic theories to measure the level of optimization: the statistical approach, which compares the canonical genetic code with many randomly generated alternative ones, and the engineering approach, which compares the canonical code with the best possible alternative. Results Here we used a genetic algorithm to search for better adapted hypothetical codes and as a method to guess the difficulty in finding such alternative codes, allowing to clearly situate the canonical code in the fitness landscape. This novel proposal of the use of evolutionary computing provides a new perspective in the open debate between the use of the statistical approach, which postulates that the genetic code conserves amino acid properties far better than expected from a random code, and the engineering approach, which tends to indicate that the canonical genetic code is still far from optimal. We used two models of hypothetical codes: one that reflects the known examples of codon reassignment and the model most used in the two approaches which reflects the current genetic code translation table. Although the standard code is far from a possible optimum considering both models, when the more realistic model of the codon reassignments was used, the evolutionary algorithm had more difficulty to overcome the efficiency of the canonical genetic code. Conclusions Simulated evolution clearly reveals that the canonical genetic code is far from optimal regarding its optimization. Nevertheless, the efficiency of the canonical code increases when mistranslations are taken into account with the two models, as indicated by the

  13. A nurse-led 'stop smoking' initiative.

    Science.gov (United States)

    McGowan, E; MacAuley, D; Anderson, U

    A one-week smoking awareness initiative and subsequent audit in a general practice are described. All patients attending morning surgery during the study period were offered the opportunity to discuss smoking habits at a smoking awareness clinic: 84 smokers attended. They were interviewed by the practice preventive care nurse who took a smoking history, monitored carbon monoxide (CO Hb) levels and offered a follow-up appointment. CO Hb provided immediate feedback on the effect of smoking and patients who smoked 20 or more cigarettes per day had an average CO Hb of 16.1 per cent. Fifteen per cent of smokers made a commitment to stop smoking and agreed to attend follow-up clinics. A random sample (50) of attenders at the initial Smoking Awareness Clinic (84) were followed up by questionnaire six months later. There were 29 replies (58 per cent); 19 patients (65 per cent) found the visit to the clinic helpful, 14 (48 per cent) reduced the number of cigarettes they smoked, and 11 (38 per cent) altered some other aspect of their lifestyle, of whom four modified their diet and four increased exercise. Five patients claimed they had given up smoking.

  14. Range and stopping power for slow particles

    International Nuclear Information System (INIS)

    Bastiano, M.; Fernandez, J. E.; Molinari, V. G.

    1997-01-01

    Generally, the effects of thermal agitation and chemical bonding of the target atoms need to be taken into account to compute properly the range and stopping power of particles. These two effects, however, complicate very much the calculation of the above parameters, and for this reason are usually neglected. In fact, when the energy of the test particles (t.p.) is sufficiently high compared to the thermal or bonding energies, these two effects can be safely disregarded. When the energy of the t.p. is of the same order of the thermal agitation or the chemical bonding, on the other hand, such approximation is not realistic, and to obtain meaningful results one must take into account the velocity distribution of the field particles (f.p.). The aim of this paper is to present a simple model describing the transport of particles (e.g., electrons) in the thermal zone, considering the thermal agitation of f.p. with an arbitrary distribution. It will be shown that in the first part of the slowing down the kinetic energy of t.p. is partially transformed into temperature. In the second part, the temperature tends to reach the equilibrium temperature, while average velocity of t.p. becomes zero. (author)

  15. Towards the end of the technical stop

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    After several weeks of hard work, the short technical stop of the LHC accelerator is coming to an end. Following a very intense campaign to repair and retest many thousand high voltage connectors, the upgraded magnet protection system is being commissioned. During this period, the current in the main dipole and quadrupole magnets is carefully increased up to 6kA, required to collide protons at 7TeV centre-of-mass energy. This has been achieved for most of the sectors.   The parameters of the upgraded magnet protection system are accurately calibrated. This operation is needed in order for the magnet protection system to be triggered only when a real problem occurs. The system is now able to detect a transition from superconducting to normal conducting state of the superconducting cable joints between magnets, a necessary condition to operate the magnet system above 2kA. Highly accurate measurements of the joint resistances have been performed by stepping up the current to 5kA. The magnets and the...

  16. 49 CFR 37.201 - Intermediate and rest stops.

    Science.gov (United States)

    2010-10-01

    ... wheelchair, shall be permitted to leave and return to the bus on the same basis as other passengers. The... passenger to get on and off the bus at the stop (e.g., operate the lift and provide assistance with... DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.201 Intermediate and rest stops. (a) Whenever an OTRB makes...

  17. Stop valve with automatic control and locking for nuclear reactors

    International Nuclear Information System (INIS)

    Chung, D.K.

    1980-01-01

    This invention generally concerns an automatic control and locking stop valve. Specifically it relates to the use of such a valve in a nuclear reactor of the type containing absorber elements supported by a fluid and intended for stopping the reactor in complete safety [fr

  18. Effect of Weight Transfer on a Vehicle's Stopping Distance.

    Science.gov (United States)

    Whitmire, Daniel P.; Alleman, Timothy J.

    1979-01-01

    An analysis of the minimum stopping distance problem is presented taking into account the effect of weight transfer on nonskidding vehicles and front- or rear-wheels-skidding vehicles. Expressions for the minimum stopping distances are given in terms of vehicle geometry and the coefficients of friction. (Author/BB)

  19. STOP4-7 Nederland. Resultaten 2010-2011

    NARCIS (Netherlands)

    Geijsen, L.; Veerman, J.W.; Bastiaanssen, I.L.W.

    2011-01-01

    STOP4-7 is een multimodale interventie voor kinderen van 4 tot 7 jaar met ernstige externaliserende gedragsproblemen en hun opvoeders en leerkrachten. Het doel van STOP4-7 is het aanleren en versterken van sociale en probleemoplossende vaardigheden en het verminderen van ongewenst gedrag. Daarvoor

  20. Ion Stopping Powers and Ranges Whenever You Need Them

    DEFF Research Database (Denmark)

    Bassler, Niels; Christensen, Casper; Tørresø, Jesper Rosholm

    A new app "Electronic Stopping Power" for Android mobile phones and tablets, looks up stopping powers using the ICRU 49 (protons and alphas) and the revised ICRU 73 (lithium and heavier ions) tables. In addition, also MSTAR and an implementation of the Bethe equation expanded to low energies...

  1. Note on measuring electronic stopping of slow ions

    Science.gov (United States)

    Sigmund, P.; Schinner, A.

    2017-11-01

    Extracting stopping cross sections from energy-loss measurements requires careful consideration of the experimental geometry. Standard procedures for separating nuclear from electronic stopping treat electronic energy loss as a friction force, ignoring its dependence on impact parameter. In the present study we find that incorporating this dependence has a major effect on measured stopping cross sections, in particular for light ions at low beam energies. Calculations have been made for transmission geometry, nuclear interactions being quantified by Bohr-Williams theory of multiple scattering on the basis of a Thomas-Fermi-Molière potential, whereas electronic interactions are characterized by Firsov theory or PASS code. Differences between the full and the restricted stopping cross section depend on target thickness and opening angle of the detector and need to be taken into account in comparisons with theory as well as in applications of stopping data. It follows that the reciprocity principle can be violated when checked on restricted instead of full electronic stopping cross sections. Finally, we assert that a seeming gas-solid difference in stopping of low-energy ions is actually a metal-insulator difference. In comparisons with experimental results we mostly consider proton data, where nuclear stopping is only a minor perturbation.

  2. Influence of certain forces on evolution of synonymous codon usage bias in certain species of three basal orders of aquatic insects.

    Science.gov (United States)

    Selva Kumar, C; Nair, Rahul R; Sivaramakrishnan, K G; Ganesh, D; Janarthanan, S; Arunachalam, M; Sivaruban, T

    2012-12-01

    Forces that influence the evolution of synonymous codon usage bias are analyzed in six species of three basal orders of aquatic insects. The rationale behind choosing six species of aquatic insects (three from Ephemeroptera, one from Plecoptera, and two from Odonata) for the present analysis is based on phylogenetic position at the basal clades of the Order Insecta facilitating the understanding of the evolution of codon bias and of factors shaping codon usage patterns in primitive clades of insect lineages and their subtle differences in some of their ecological and environmental requirements in terms of habitat-microhabitat requirements, altitudinal preferences, temperature tolerance ranges, and consequent responses to climate change impacts. The present analysis focuses on open reading frames of the 13 protein-coding genes in the mitochondrial genome of six carefully chosen insect species to get a comprehensive picture of the evolutionary intricacies of codon bias. In all the six species, A and T contents are observed to be significantly higher than G and C, and are used roughly equally. Since transcription hypothesis on codon usage demands A richness and T poorness, it is quite likely that mutation pressure may be the key factor associated with synonymous codon usage (SCU) variations in these species because the mutation hypothesis predicts AT richness and GC poorness in the mitochondrial DNA. Thus, AT-biased mutation pressure seems to be an important factor in framing the SCU variation in all the selected species of aquatic insects, which in turn explains the predominance of A and T ending codons in these species. This study does not find any association between microhabitats and codon usage variations in the mitochondria of selected aquatic insects. However, this study has identified major forces, such as compositional constraints and mutation pressure, which shape patterns of codon usage in mitochondrial genes in the primitive clades of insect lineages.

  3. Inertial-confinement-fusion applications of ion-stopping theory

    International Nuclear Information System (INIS)

    More, R.M.; Lee, Y.T.; Bailey, D.S.

    1982-01-01

    Methods were developed to calculate: (1) the stopping power of a hot plasma target, (2) the charge-state of a fast ion projectile, and (3) the final disposition of the deposited energy. The first issue refers to the stopping power for protons. The proton stopping power is altered in high-density or high-temperature targets, especially at velocities below the stopping peak. The second issue concerns the application of a proton stopping curve to the arbitrary projectile. The third topic is more specialized to inertial fusion and concerns the partition of deposited energy between ion (nuclear motion) degrees of freedom and those corresponding to bound and free electrons. The question here is whether a thermal equilibrium plasma is produced

  4. Simulating fail-stop in asynchronous distributed systems

    Science.gov (United States)

    Sabel, Laura; Marzullo, Keith

    1994-01-01

    The fail-stop failure model appears frequently in the distributed systems literature. However, in an asynchronous distributed system, the fail-stop model cannot be implemented. In particular, it is impossible to reliably detect crash failures in an asynchronous system. In this paper, we show that it is possible to specify and implement a failure model that is indistinguishable from the fail-stop model from the point of view of any process within an asynchronous system. We give necessary conditions for a failure model to be indistinguishable from the fail-stop model, and derive lower bounds on the amount of process replication needed to implement such a failure model. We present a simple one-round protocol for implementing one such failure model, which we call simulated fail-stop.

  5. High fluence effects on ion implantation stopping and range

    International Nuclear Information System (INIS)

    Selvi, S.; Tek, Z.; Oeztarhan, A.; Akbas, N.; Brown, I.G.

    2005-01-01

    We have developed a code STOPPO which can be used to modify the more-widely used ion implantation codes to more accurately predict the mean nuclear and electronic stopping power, preferential sputtering and range of heavy ions in monatomic target materials. In our simulations an effective atomic number and effective atomic mass are introduced into conveniently available analytical stopping cross-sections and a better fitting function for preferential sputtering yield is carefully evaluated for each ion implantation. The accuracy of the code confirmed experimentally by comparison with measured Rutherford backscattering spectrometry (RBS) concentration profiles for 130 keV Zr ions implanted into Be to fluences of 1 x 10 17 , 2 x 10 17 and 4 x 10 17 ions/cm 2 . We find a steady increase in the mean nuclear and electronic stopping powers of the target; the increase in nuclear stopping power is much greater than the increase in electronic stopping power

  6. Evidence of codon usage in the nearest neighbor spacing distribution of bases in bacterial genomes

    Science.gov (United States)

    Higareda, M. F.; Geiger, O.; Mendoza, L.; Méndez-Sánchez, R. A.

    2012-02-01

    Statistical analysis of whole genomic sequences usually assumes a homogeneous nucleotide density throughout the genome, an assumption that has been proved incorrect for several organisms since the nucleotide density is only locally homogeneous. To avoid giving a single numerical value to this variable property, we propose the use of spectral statistics, which characterizes the density of nucleotides as a function of its position in the genome. We show that the cumulative density of bases in bacterial genomes can be separated into an average (or secular) plus a fluctuating part. Bacterial genomes can be divided into two groups according to the qualitative description of their secular part: linear and piecewise linear. These two groups of genomes show different properties when their nucleotide spacing distribution is studied. In order to analyze genomes having a variable nucleotide density, statistically, the use of unfolding is necessary, i.e., to get a separation between the secular part and the fluctuations. The unfolding allows an adequate comparison with the statistical properties of other genomes. With this methodology, four genomes were analyzed Burkholderia, Bacillus, Clostridium and Corynebacterium. Interestingly, the nearest neighbor spacing distributions or detrended distance distributions are very similar for species within the same genus but they are very different for species from different genera. This difference can be attributed to the difference in the codon usage.

  7. The global polio eradication initiative Stop Transmission of Polio (STOP) program - 1999-2013.

    Science.gov (United States)

    2013-06-21

    In 1988, the Global Polio Eradication Initiative (GPEI) was established through a partnership between the World Health Organization (WHO), Rotary International, CDC, and the United Nations Children's Fund (UNICEF). By 2012, the annual incidence of polio had decreased by >99%, compared with 1988, and the number of countries in which wild poliovirus (WPV) circulation has never been interrupted was reduced to three: Afghanistan, Nigeria, and Pakistan. However, because of the persistence of endemic WPV transmission and recurring outbreaks in polio-free countries after the original polio eradication target date of 2000, the World Health Assembly in 2012 declared the completion of polio eradication a programmatic emergency. A key component of GPEI is the Stop Transmission of Polio (STOP) program, which was developed and initiated by CDC with WHO in 1999 to mobilize additional human resources and technical assistance for countries affected by WPV transmission. During 1999-2013, 1,563 volunteers were identified, trained, and deployed for 2,221 assignments in 69 countries. The number of volunteers increased from 90-120 per year during 1999-2011 to 287 in 2012 and 378 in 2013, and the number of volunteer person-months in the field per year increased from 273 in 1999 to 1,456 in 2012. The STOP program has aided GPEI by strengthening the capacity of country-level immunization programs and by allowing a large cohort of volunteers to gain valuable field experience that prepares them well for subsequent work as staff members of WHO, UNICEF, and other public health agencies.

  8. Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion protein at codon 180

    International Nuclear Information System (INIS)

    Ishida, S.; Sugino, M.; Shinoda, K.; Ohsawa, N.; Koizumi, N.; Ohta, T.; Kitamoto, T.; Tateishi, J.

    1995-01-01

    We report a 66-year-old woman with histologically diagnosed Creutzfeld-Jacob disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated expansion of the high cortical signal on T2-weighted images, which differs from previous MRI reports of CJD. This patient followed an atypical clinical course: 16 months had passed before she developed akinetic mutism, and periodic sharp waves had not been detected on EEG after 2 years in spite of her akinetic mutism. Brain biopsy showed primary spongiform changes in the grey matter, and a point mutation of the prion protein gene at codon 180 was discovered using polymerase chain reaction direct sequencing and Tth 111 I cutting. This is the first case with the point mutation of the codon 180 variant with an atypical clinical course and characteristic MRI findings. (orig.)

  9. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A

    2002-01-01

    on parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin......, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels......AIMS: The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism...

  10. A System for Anesthesia Drug Administration Using Barcode Technology: The Codonics Safe Label System and Smart Anesthesia Manager.

    Science.gov (United States)

    Jelacic, Srdjan; Bowdle, Andrew; Nair, Bala G; Kusulos, Dolly; Bower, Lynnette; Togashi, Kei

    2015-08-01

    Many anesthetic drug errors result from vial or syringe swaps. Scanning the barcodes on vials before drug preparation, creating syringe labels that include barcodes, and scanning the syringe label barcodes before drug administration may help to prevent errors. In contrast, making syringe labels by hand that comply with the recommendations of regulatory agencies and standards-setting bodies is tedious and time consuming. A computerized system that uses vial barcodes and generates barcoded syringe labels could address both safety issues and labeling recommendations. We measured compliance of syringe labels in multiple operating rooms (ORs) with the recommendations of regulatory agencies and standards-setting bodies before and after the introduction of the Codonics Safe Label System (SLS). The Codonics SLS was then combined with Smart Anesthesia Manager software to create an anesthesia barcode drug administration system, which allowed us to measure the rate of scanning syringe label barcodes at the time of drug administration in 2 cardiothoracic ORs before and after introducing a coffee card incentive. Twelve attending cardiothoracic anesthesiologists and the OR satellite pharmacy participated. The use of the Codonics SLS drug labeling system resulted in >75% compliant syringe labels (95% confidence interval, 75%-98%). All syringe labels made using the Codonics SLS system were compliant. The average rate of scanning barcodes on syringe labels using Smart Anesthesia Manager was 25% (730 of 2976) over 13 weeks but increased to 58% (956 of 1645) over 8 weeks after introduction of a simple (coffee card) incentive (P < 0.001). An anesthesia barcode drug administration system resulted in a moderate rate of scanning syringe label barcodes at the time of drug administration. Further, adaptation of the system will be required to achieve a higher utilization rate.

  11. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice.

    Science.gov (United States)

    Wanner, Roger M; Güthlein, Carolin; Springer, Burkhard; Böttger, Erik C; Ackermann, Martin

    2008-05-28

    The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  12. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice

    Directory of Open Access Journals (Sweden)

    Ackermann Martin

    2008-05-01

    Full Text Available Abstract Background The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. Results We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. Conclusion These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  13. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634).

    Science.gov (United States)

    Jesić, Maja D; Tancić-Gajić, Milina; Jesić, Milos M; Zivaljević, Vladan; Sajić, Silvija; Vujović, Svetlana; Damjanović, Svetozar

    2014-01-01

    The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. This is a case report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  14. Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.

    Science.gov (United States)

    Lavania, Mallika; Hena, Abu; Reja, Hasanoor; Nigam, Astha; Biswas, Nibir Kumar; Singh, Itu; Turankar, Ravindra P; Gupta, Ud; Kumar, Senthil; Rewaria, Latika; Patra, Pradip K R; Sengupta, Utpal; Bhattacharya, Basudeb

    2016-03-01

    Rifampicin is the major drug in the treatment of leprosy. The rifampicin resistance of Mycobacterium leprae results from a mutation in the rpoB gene, encoding the β subunit of RNA polymerase. As M. leprae is a non-cultivable organism observation of its growth using mouse food-pad (MFP) is the only Gold Standard assay used for confirmation of "in-vivo" drug resistance. Any mutation at molecular level has to be verified by MFP assay for final confirmation of drug resistance in leprosy. In the present study, M. leprae strains showing a mutation only at codon 442 Gln-His and along with mutation either at codon 424 Val-Gly or at 438 Gln-Val within the Rifampicin Resistance Determining Region (RRDR) confirmed by DNA sequencing and by high resolution melting (HRM) analysis were subjected for its growth in MFP. The M. leprae strain having the new mutation at codon 442 Gln-His was found to be sensitive to all the three drugs and strains having additional mutations at 424 Val-Gly and 438 Gln-Val were conferring resistance with Multi drug therapy (MDT) in MFP. These results indicate that MFP is the gold standard method for confirming the mutations detected by molecular techniques.

  15. Functional role of bacteriophage transfer RNAs: codon usage analysis of genomic sequences stored in the GENBANK/EMBL/DDBJ databases

    Directory of Open Access Journals (Sweden)

    T Kunisawa

    2006-01-01

    Full Text Available Complete genomic sequence data are stored in the public GenBank/EMBL/DDBJ databases so that any investigator can make use of the data. This report describes a comparative analysis of codon usage that is impossible without such a public and open data system. A limited number of bacteriophages harbor their own transfer RNAs. Based on a comparison between T4 phage-encoded tRNA species and the relative cellular amounts of host Escherichia coli tRNAs, it is hypothesized that T4 tRNAs could serve to supplement host isoacceptor tRNA species that are present in minor amounts and thus enhance the translational efficiency of phage proteins. When compared to their respective host bacteria, the codon usage data of bacteriophages D3, φC31, HP1, D29 and 933W all show an increased frequency of synonymous codons or amino acids that correspond to phage tRNA species, suggesting their supplemental role in the efficient production of phage proteins. The data-analysis presents an example in which the availability of an open and fully accessible database system would allow one to obtain comprehensive insights into a fundamental problem in molecular biology.

  16. When to stop drying fruit: Insights from hygrothermal modelling

    International Nuclear Information System (INIS)

    Defraeye, Thijs

    2017-01-01

    Highlights: • Partial dehydration reduces energy consumption and processing time and improves product quality. • This study gives a quantitative insight in when fruit drying should be stopped. • Decrease in dryer residence time of 2%, 24% and 70% are found for different stopping criteria. - Abstract: Stopping the drying process prior to complete dehydration reduces energy consumption and processing time but can also improve product quality. Using hygrothermal simulations, different stopping criteria are evaluated, which are based on the final water activity and residual moisture content in the fruit. Their impact on drying time and moisture redistribution kinetics inside fruit is quantified. One of the variants leads to a significant reduction in residence time in the dryer (24%), compared to full dehydration. For this variant, drying is stopped when the average moisture content in the sample reaches the value corresponding to an equilibrium water activity of 60% in the sample, as determined from the sorption isotherm. At the same time, this variant does not induce problems with fruit spoilage, as a sufficiently low water activity is reached after moisture redistribution during relaxation in the ambient environment. In addition, the relation of the drying time to the drying air temperature was quantified for all stopping criteria, as well as the impact of the humidity of the ambient environment in which the dried fruits are placed afterwards. This study gives a better quantitative insight in when fruit drying should be stopped, given specific drying conditions, without having to compromise food safety.

  17. STARCODES, Stopping Power and Ranges for Electrons, Protons, He

    International Nuclear Information System (INIS)

    2000-01-01

    1 - Description of program or function: The 'STAR CODES', ESTAR, PSTAR, and ASTAR, calculate stopping-power and range tables for electrons, protons, and helium ions (alphas), according to methods described in ICRU Reports 37 and 39. 2 - Method of solution: Collision stopping powers are calculated from the theory of Bethe (1930, 1932), with a density-effect correction evaluated according to Sternheimer (1952, 1982). The stopping-power formula contains an important parameter, the mean excitation energy (I-value), which characterizes the stopping properties of a material. The codes provide output for electrons in any stopping material (279 provided) and for protons and helium ions in 74 materials. The calculations include the 1) Collision stopping power, 2) Radiative stopping power (electrons only), 3) Nuclear stopping power (protons and helium ions), 4) Total stopping power, 5) CSDA range, 6) Projected range (protons and helium ions), 7) Density effect parameter (electrons), 8) Radiation yield (electrons), and 9) Detour factor (protons and helium ions). Standard energy grids and files of elements w/ionization-excitation information are included with lookup table capabilities. 3 - Restrictions on the complexity of the problem: The minimum energies used in the calculations are at 1 KeV (protons and helium ions) and 10 KeV (electrons), and the maximum are 1 GeV. The standard energy grids are set at 81 for electrons, equally spaced (logarithmically), 133 for protons, and 122 for helium ions. The lower energy electron calculations (< 10 KeV) have up to 5-10% errors and are considered too fallable

  18. Stop search in the compressed region via semileptonic decays

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Hsin-Chia; Gao, Christina; Li, Lingfeng; Neill, Nicolás A. [Department of Physics, University of California,Davis, California 95616 (United States)

    2016-05-05

    In supersymmetric extensions of the Standard Model, the superpartners of the top quark (stops) play the crucial role in addressing the naturalness problem. For direct pair-production of stops with each stop decaying into a top quark plus the lightest neutralino, the standard stop searches have difficulty finding the stop for a compressed spectrum where the mass difference between the stop and the lightest neutralino is close to the top quark mass, because the events look too similar to the large tt̄ background. With an additional hard ISR jet, the two neutralinos from the stop decays are boosted in the opposite direction and they can give rise to some missing transverse energy. This may be used to distinguish the stop decays from the backgrounds. In this paper we study the semileptonic decay of such signal events for the compressed mass spectrum. Although the neutrino from the W decay also produces some missing transverse energy, its momentum can be reconstructed from the kinematic assumptions and mass-shell conditions. It can then be subtracted from the total missing transverse momentum to obtain the neutralino contribution. Because it suffers from less backgrounds, we show that the semileptonic decay channel has a better discovery reach than the fully hadronic decay channel along the compressed line m{sub t̃}−m{sub χ̃}≈m{sub t}. With 300 fb{sup −1}, the 13 TeV LHC can discover the stop up to 500 GeV, covering the most natural parameter space region.

  19. Efficient Coproduction of Mannanase and Cellulase by the Transformation of a Codon-Optimized Endomannanase Gene from Aspergillus niger into Trichoderma reesei.

    Science.gov (United States)

    Sun, Xianhua; Xue, Xianli; Li, Mengzhu; Gao, Fei; Hao, Zhenzhen; Huang, Huoqing; Luo, Huiying; Qin, Lina; Yao, Bin; Su, Xiaoyun

    2017-12-20

    Cellulase and mannanase are both important enzyme additives in animal feeds. Expressing the two enzymes simultaneously within one microbial host could potentially lead to cost reductions in the feeding of animals. For this purpose, we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of Trichoderma reesei. By comparing the free energies and the local structures of the nucleotide sequences, one optimized sequence was finally selected and transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon-optimized gene was expressed to a higher level than the original one. Further expressing the codon-optimized gene in a mutated T. reesei strain through fed-batch cultivation resulted in coproduction of cellulase and mannanase up to 1376 U·mL -1 and 1204 U·mL -1 , respectively.

  20. Stopping power. Projectile and target modeled as oscillators

    International Nuclear Information System (INIS)

    Stevanovic, N.; Nikezic, D.

    2005-01-01

    In this Letter the collision of two quantum harmonic oscillators was considered. The oscillators interact through the Coulomb interaction. Stopping power of projectile was calculated assuming that both, target and projectile may be excited. It has been shown that the frequency of the projectile oscillation, ω p influences on stopping power, particularly in the region of Bragg peak. If, ω p ->0 is substitute in the expression for stopping power derived in this Letter, then it comes to the form when the projectile has been treated as point like charged particle

  1. ELectron stopping of heavy ions in a matter

    International Nuclear Information System (INIS)

    Akhiezer, I.A.; Davydov, L.N.

    1978-01-01

    The theory of heavy ion stopping by electrons in solids is analyzed with an aim to establish which physical mechanisms are of importance at different ion velocity values v. The theory is presented for deep inelastic collisions taking the main part in stopping at v > Zsub(1)sup(1/3) v 0 (z 1 is the atomic number of the ion, v 0 is the Bohr velocity). Elastic scattering (relative to the incident ion) are investigated. It is shown that the contribution from these processes to the stopping cross-section is predominant at Zsub(1)sup(1/3) v 0 > v > Zsub(1)sup(2/3) v 0

  2. A Phonemic and Acoustic Analysis of Hindko Oral Stops

    Directory of Open Access Journals (Sweden)

    Haroon Ur RASHID

    2014-12-01

    Full Text Available Hindko is an Indo-Aryan language that is mainly spoken in Khyber Pukhtoonkhaw province of Pakistan. This work aims to identify the oral stops of Hindko and determine the intrinsic acoustic cues for them. The phonemic analysis is done with the help of minimal pairs and phoneme distribution in contrastive environments which reveals that Hindko has twelve oral stops with three way series. The acoustic analysis of these segments shows that intrinsically voice onset time (VOT, closure duration and burst are reliable and distinguishing cues of stops in Hindko.

  3. Start codon targeted (scot polymorphism reveals genetic diversity in european old maize (zea mays l. Genotypes

    Directory of Open Access Journals (Sweden)

    Martin Vivodík

    2016-11-01

    Full Text Available Maize (Zea mays L. is one of the world's most important crop plants following wheat and rice, which provides staple food to large number of human population in the world. It is cultivated in a wider range of environments than wheat and rice because of its greater adaptability. Molecular characterization is frequently used by maize breeders as an alternative method for selecting more promising genotypes and reducing the cost and time needed to develop hybrid combinations. In the present investigation 40 genotypes of maize from Czechoslovakia, Hungary, Poland, Union of Soviet Socialist Republics, Slovakia and Yugoslavia were analysed using 20 Start codon targeted (SCoT markers. These primers produced total 114 fragments across 40 maize genotypes, of which 86 (76.43% were polymorphic with an average of 4.30 polymorphic fragments per primer and number of amplified fragments ranged from 2 (SCoT 45 to 8 (SCoT 28 and SCoT 63. The polymorphic information content (PIC value ranged from 0.374 (ScoT 45 to 0.846 (SCoT 28 with an average of 0.739. The dendrogram based on hierarchical cluster analysis using UPGMA algorithm was prepared. The hierarchical cluster analysis showed that the maize genotypes were divided into two main clusters. Unique maize genotype (cluster 1, Zuta Brzica, originating from Yugoslavia separated from others. Cluster 2 was divided into two main clusters (2a and 2b. Subcluster 2a contained one Yugoslavian genotype Juhoslavanska and subcluster 2b was divided in two subclusters 2ba and 2bb. The present study shows effectiveness of employing SCoT markers in analysis of maize, and would be useful for further studies in population genetics, conservation genetics and genotypes improvement.

  4. TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2007-11-01

    Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

  5. Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes*

    Science.gov (United States)

    Takeuchi, Atsuko; Kobayashi, Atsushi; Ironside, James W.; Mohri, Shirou; Kitamoto, Tetsuyuki

    2013-01-01

    To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein (PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in individuals with a PRNP codon 129 genotype other than M/M and transmission studies using animal models have raised the concern that all humans might be susceptible to vCJD prions, especially via secondary infection. To reevaluate this possibility and to analyze in detail the transmission properties of vCJD prions to transgenic animals carrying distinct codon 129 genotype, we performed intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in mouse lines were susceptible to vCJD infection, although the attack rate gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP deposition including florid/amyloid plaques in the brain also gradually decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of protease-resistant abnormal PrP in the brain and transmissibility of these humanized mouse-passaged vCJD prions upon subpassage into knock-in mice expressing bovine PrP were not affected by the codon 129 genotype. These results indicate that individuals with the 129V/V genotype may be more susceptible to secondary vCJD infection than expected and may lack the neuropathological characteristics observed in vCJD patients with the 129M/M genotype. Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype. PMID:23792955

  6. Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes.

    Science.gov (United States)

    Takeuchi, Atsuko; Kobayashi, Atsushi; Ironside, James W; Mohri, Shirou; Kitamoto, Tetsuyuki

    2013-07-26

    To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein (PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in individuals with a PRNP codon 129 genotype other than M/M and transmission studies using animal models have raised the concern that all humans might be susceptible to vCJD prions, especially via secondary infection. To reevaluate this possibility and to analyze in detail the transmission properties of vCJD prions to transgenic animals carrying distinct codon 129 genotype, we performed intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in mouse lines were susceptible to vCJD infection, although the attack rate gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP deposition including florid/amyloid plaques in the brain also gradually decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of protease-resistant abnormal PrP in the brain and transmissibility of these humanized mouse-passaged vCJD prions upon subpassage into knock-in mice expressing bovine PrP were not affected by the codon 129 genotype. These results indicate that individuals with the 129V/V genotype may be more susceptible to secondary vCJD infection than expected and may lack the neuropathological characteristics observed in vCJD patients with the 129M/M genotype. Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype.

  7. Identification and codon reading properties of 5-cyanomethyl uridine, a new modified nucleoside found in the anticodon wobble position of mutant haloarchaeal isoleucine tRNAs.

    Science.gov (United States)

    Mandal, Debabrata; Köhrer, Caroline; Su, Dan; Babu, I Ramesh; Chan, Clement T Y; Liu, Yuchen; Söll, Dieter; Blum, Paul; Kuwahara, Masayasu; Dedon, Peter C; Rajbhandary, Uttam L

    2014-02-01

    Most archaea and bacteria use a modified C in the anticodon wobble position of isoleucine tRNA to base pair with A but not with G of the mRNA. This allows the tRNA to read the isoleucine codon AUA without also reading the methionine codon AUG. To understand why a modified C, and not U or modified U, is used to base pair with A, we mutated the C34 in the anticodon of Haloarcula marismortui isoleucine tRNA (tRNA2(Ile)) to U, expressed the mutant tRNA in Haloferax volcanii, and purified and analyzed the tRNA. Ribosome binding experiments show that although the wild-type tRNA2(Ile) binds exclusively to the isoleucine codon AUA, the mutant tRNA binds not only to AUA but also to AUU, another isoleucine codon, and to AUG, a methionine codon. The G34 to U mutant in the anticodon of another H. marismortui isoleucine tRNA species showed similar codon binding properties. Binding of the mutant tRNA to AUG could lead to misreading of the AUG codon and insertion of isoleucine in place of methionine. This result would explain why most archaea and bacteria do not normally use U or a modified U in the anticodon wobble position of isoleucine tRNA for reading the codon AUA. Biochemical and mass spectrometric analyses of the mutant tRNAs have led to the discovery of a new modified nucleoside, 5-cyanomethyl U in the anticodon wobble position of the mutant tRNAs. 5-Cyanomethyl U is present in total tRNAs from euryarchaea but not in crenarchaea, eubacteria, or eukaryotes.

  8. Canine parvovirus type 2 (CPV-2) and Feline panleukopenia virus (FPV) codon bias analysis reveals a progressive adaptation to the new niche after the host jump.

    Science.gov (United States)

    Franzo, Giovanni; Tucciarone, Claudia Maria; Cecchinato, Mattia; Drigo, Michele

    2017-09-01

    Based on virus dependence from host cell machinery, their codon usage is expected to show a strong relation with the host one. Even if this association has been stated, especially for bacteria viruses, the linkage is considered to be less consistent for more complex organisms and a codon bias adaptation after host jump has never been proven. Canine parvovirus type 2 (CPV-2) was selected as a model because it represents a well characterized case of host jump, originating from Feline panleukopenia virus (FPV). The current study demonstrates that the adaptation to specific tissue and host codon bias affected CPV-2 evolution. Remarkably, FPV and CPV-2 showed a higher closeness toward the codon bias of the tissues they display the higher tropism for. Moreover, after the host jump, a clear and significant trend was evidenced toward a reduction in the distance between CPV-2 and the dog codon bias over time. This evidence was not confirmed for FPV, suggesting that an equilibrium has been reached during the prolonged virus-host co-evolution. Additionally, the presence of an intermediate pattern displayed by some strains infecting wild species suggests that these could have facilitated the host switch also by acting on codon bias. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Association between the p53 codon 72 polymorphism and primary open-angle glaucoma risk: Meta-analysis based on 11 case–control studies

    Directory of Open Access Journals (Sweden)

    Mohsen Gohari

    2016-01-01

    Full Text Available The TP53 is important in functions of cell cycle control, apoptosis, and maintenance of DNA integrity. Studies on the association between p53 codon 72 polymorphism and primary open-angle glaucoma (POAG risk have yielded conflicting results. Published literature from PubMed and Web of Science databases was retrieved. All studies evaluating the association between p53 codon 72 polymorphisms and POAG were included. Pooled odds ratio (OR and 95% confidence interval (CI were calculated. Eleven separate studies including 2541 cases and 1844 controls were pooled in the meta-analysis. We did not detect a significant association between POAG risk and p53 codon 72 polymorphism overall population except allele genetic model (C vs. G: OR = 0.961, 95% CI = 0.961–0.820, P = 0.622. In the stratified analysis for Asians and Caucasians, there was an association between p53 codon 72 polymorphism and POAG. In the dominant model in the overall population and by ethnicity subgroups, the highest elevated POAG risk was presented. In summary, these results indicate that p53 codon 72 polymorphism is likely an important genetic factor contributing to susceptibility of POAG. However, more case–controls studies based on larger sample size and stratified by ethnicity are suggested to further clarify the relationship between p53 codon 72 polymorphism and POAG.

  10. Optimal Locations of Bus Stops Connecting Subways near Urban Intersections

    Directory of Open Access Journals (Sweden)

    Yuan Cui

    2015-01-01

    Full Text Available Unsuitable locations of bus stops which provide feeder transportation connecting subways near urban intersections usually lead to the low efficiency of public transport and level of passenger service. A multiobjective optimization model to distribute such stop locations is proposed to attain the shortest total walk distance of passengers and minimum delay time of cars through intersections and travel time of buses. The Pareto frontier and optimal solutions for the proposed model are given by the distance-based and enumerative methods. The Xizhimen bus stop is selected to implement case studies for verifying the validity of the proposed model. The analysis of sensitivity on possible solutions is also carried out in the case studies. The results show that the proposed model is capable of optimizing the locations of bus stops connecting subways near intersections and helpful to improve the level of passengers service and operational efficiency of public transportation.

  11. Observations of NC stop nets for bottlenose dolphin takes

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — To observe the NC stop net fishery to document the entanglement of bottlenose dolphins and movement of dolphins around the nets.

  12. Kidney Dialysis: When Is It Time to Stop?

    Science.gov (United States)

    ... is it time to stop? My 82-year-old husband has been on kidney dialysis for a ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  13. Analysis of movable bus stop boarding and alighting areas.

    Science.gov (United States)

    2013-05-01

    This study explored the feasibility of using movable and reusable boarding and alighting (B&A) pads at bus stops. : Potential design alternatives in terms of materials and structural support for these pads were evaluated. The review : focused on the ...

  14. Higgs-Stoponium Mixing Near the Stop-Antistop Threshold

    CERN Document Server

    Bodwin, Geoffrey T; Wagner, Carlos E M

    2016-01-01

    Supersymmetric extensions of the standard model contain additional heavy neutral Higgs bosons that are coupled to heavy scalar top quarks (stops). This system exhibits interesting field theoretic phenomena when the Higgs mass is close to the stop-antistop production threshold. Existing work in the literature has examined the digluon-to-diphoton cross section near threshold and has focused on enhancements in the cross section that might arise either from the perturbative contributions to the Higgs-to-digluon and Higgs-to-diphoton form factors or from mixing of the Higgs boson with stoponium states. Near threshold, enhancements in the relevant amplitudes that go as inverse powers of the stop-antistop relative velocity require resummations of perturbation theory and/or nonperturbative treatments. We present a complete formulation of threshold effects at leading order in the stop-antistop relative velocity in terms of nonrelativistic effective field theory. We give detailed numerical calculations for the case in ...

  15. Density dependence of stopping cross sections measured in liquid ethane

    International Nuclear Information System (INIS)

    Both, G.; Krotz, R.; Lohmer, K.; Neuwirth, W.

    1983-01-01

    Electronic stopping cross sections for 7 Li projectiles (840--175 keV) have been measured with the inverted Doppler-shift attenuation method in liquid ethane (C 2 H 6 ) at two different densities. The density of the target has been varied by changing the temperature, and measurements have been performed at 0.525 g/cm 3 (199 K) and 0.362 g/cm 3 (287 K). At the higher density the stopping cross section is about 2% smaller. This result agrees with a calculation of the stopping cross section of liquid ethane, applying Lindhard's theory in the local-density approximation using a simple model of the liquid. It is also in agreement with various observations of the so-called physical-state effect, which show that the stopping cross section of the same substance is smaller in a condensed phase than in the gaseous one

  16. On plasma coupling and turbulence effects in low velocity stopping

    Energy Technology Data Exchange (ETDEWEB)

    Kurilenkov, Yu K [Unified Institute for High Temperatures of Russian Academy of Sciences, 13/19 Izhorskaya Str., 125412 Moscow (Russian Federation); Maynard, G [Laboratoire de Physique des Gaz et des Plasmas, UMR-8578, Bat. 210, Universite Paris XI, F-91405 Orsay (France); Barriga-Carrasco, M D [Laboratoire de Physique des Gaz et des Plasmas, UMR-8578, Bat. 210, Universite Paris XI, F-91405 Orsay (France); Valuev, A A [Unified Institute for High Temperatures of Russian Academy of Sciences, 13/19 Izhorskaya Str., 125412 Moscow (Russian Federation)

    2006-04-28

    The problem of stopping power (SP) for projectile ions is analysed in terms of the dielectric function and effective collision frequency for moderately dense and strongly coupled plasmas (SCP). We consider several issues regarding the calculation of stopping power for correlated ensembles of particles and oscillators. In particular, effects of group (few particle) modes, transition from positive to negative dispersion and excitation of collective modes up to suprathermal level at plasma targets are addressed. Linear SP of dense suprathermal (nonlinear) plasma targets at different levels of target plasma turbulence is estimated. The force of suprathermal plasma oscillations on the projectile ions is mostly in the nature of increased frictional drag. The results obtained show the possibility of increasing low velocity stopping (up to 'turbulent' values) in comparison with losses in equilibrium dense plasma targets. Experimental conditions to create specific turbulent targets as well as some connection between stopping phenomena and SCP transport properties are discussed briefly.

  17. On plasma coupling and turbulence effects in low velocity stopping

    International Nuclear Information System (INIS)

    Kurilenkov, Yu K; Maynard, G; Barriga-Carrasco, M D; Valuev, A A

    2006-01-01

    The problem of stopping power (SP) for projectile ions is analysed in terms of the dielectric function and effective collision frequency for moderately dense and strongly coupled plasmas (SCP). We consider several issues regarding the calculation of stopping power for correlated ensembles of particles and oscillators. In particular, effects of group (few particle) modes, transition from positive to negative dispersion and excitation of collective modes up to suprathermal level at plasma targets are addressed. Linear SP of dense suprathermal (nonlinear) plasma targets at different levels of target plasma turbulence is estimated. The force of suprathermal plasma oscillations on the projectile ions is mostly in the nature of increased frictional drag. The results obtained show the possibility of increasing low velocity stopping (up to 'turbulent' values) in comparison with losses in equilibrium dense plasma targets. Experimental conditions to create specific turbulent targets as well as some connection between stopping phenomena and SCP transport properties are discussed briefly

  18. We Can Stop HIV One Conversation at a Time

    Centers for Disease Control (CDC) Podcasts

    As part of the We Can Stop HIV One Conversation at a Time campaign, this 30 second PSA encourages Hispanics/Latinos to talk openly about HIV and AIDS with their families, friends, partners, and communities.

  19. Stopping the Spread of Germs at Home, Work and School

    Science.gov (United States)

    ... Pandemic Other Stopping the Spread of Germs at Home, Work & School Language: English (US) Español Recommend on Facebook ... everyone from getting germs or spreading germs at home, work, or school. Clean and disinfect surfaces or objects. ...

  20. Vaccines Stop Illness | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table of ... like polio and meningitis will affect their children. Vaccine Safety In light of recent questions about vaccine ...

  1. Mechanical stop mechanism for overcoming MEMS fabrication tolerances

    International Nuclear Information System (INIS)

    Hussein, Hussein; Bourbon, Gilles; Le Moal, Patrice; Lutz, Philippe; Haddab, Yassine

    2017-01-01

    A mechanical stop mechanism is developed in order to compensate MEMS fabrication tolerances in discrete positioning. The mechanical stop mechanism is designed to be implemented on SOI wafers using a common DRIE etching process. The various fabrication tolerances obtained due to the etching process are presented and discussed in the paper. The principle and design of the mechanism are then presented. Finally, experiments on microfabricated positioning prototypes show accurate steps unaffected by the fabrication tolerances. (technical note)

  2. Station Stopping of Freight Trains with Pneumatic Braking

    OpenAIRE

    Yun Bai; Baohua Mao; Tinkin Ho; Yu Feng; Shaokuan Chen

    2014-01-01

    In Chinese mainline railway, freight trains need to stop within passenger stations at times because of the delayed passenger trains. Without any decision-support system, it is very difficult for drivers to stop trains within stations with consistency in one braking action. The reasons are that braking performance of train changes with the conditions of braking equipment and the drivers’ subjective evaluations of track profiles and braking distance are vague and imprecise. This paper presents ...

  3. Stopping power of K electrons at extreme relativistic energies

    International Nuclear Information System (INIS)

    Leung, P.T.; Rustgi, M.L.

    1983-01-01

    The recent work of Anholt on K-vacancy production by relativistic projectiles has been applied to calculate the stopping power of the K electrons. The results show that for protons of energy approx.10 3 GeV and heavy target elements, the relativistic contributions to the stopping power amount to several times the resuls due to the longitudinal terms obtained from Walske's work

  4. Motor Preparation Disrupts Proactive Control in the Stop Signal Task

    Directory of Open Access Journals (Sweden)

    Wuyi Wang

    2018-05-01

    Full Text Available In a study of the stop signal task (SST we employed Bayesian modeling to compute the estimated likelihood of stop signal or P(Stop trial by trial and identified regional processes of conflict anticipation and response slowing. A higher P(Stop is associated with prolonged go trial reaction time (goRT—a form of sequential effect—and reflects proactive control of motor response. However, some individuals do not demonstrate a sequential effect despite similar go and stop success (SS rates. We posited that motor preparation may disrupt proactive control more in certain individuals than others. Specifically, the time interval between trial and go signal onset—the fore-period (FP—varies across trials and a longer FP is associated with a higher level of motor preparation and shorter goRT. Greater motor preparatory activities may disrupt proactive control. To test this hypothesis, we compared brain activations and Granger causal connectivities of 81 adults who demonstrated a sequential effect (SEQ and 35 who did not (nSEQ. SEQ and nSEQ did not differ in regional activations to conflict anticipation, motor preparation, goRT slowing or goRT speeding. In contrast, SEQ and nSEQ demonstrated different patterns of Granger causal connectivities. P(Stop and FP activations shared reciprocal influence in SEQ but FP activities Granger caused P(Stop activities unidirectionally in nSEQ, and FP activities Granger caused goRT speeding activities in nSEQ but not SEQ. These findings support the hypothesis that motor preparation disrupts proactive control in nSEQ and provide direct neural evidence for interactive go and stop processes.

  5. Stopping power of degenerate electron liquid at metallic densities

    International Nuclear Information System (INIS)

    Tanaka, Shigenori; Ichimaru, Setsuo

    1985-01-01

    We calculate the stopping power of the degenerate electron liquid at metallic densities in the dielectric formalism. The strong Coulomb-coupling effects beyond the random-phase approximation are taken into account through the static and dynamic local-field corrections. It is shown that those strong-coupling and dynamic effects act to enhance the stopping power substantially in the low-velocity regime, leading to an improved agreement with experimental data. (author)

  6. Unsure When to Stop? Ask Your Semantic Neighbors

    OpenAIRE

    Gonçalves, Ivo; Silva, Sara; Fonseca, Carlos M.; Castelli, Mauro

    2017-01-01

    In iterative supervised learning algorithms it is common to reach a point in the search where no further induction seems to be possible with the available data. If the search is continued beyond this point, the risk of overfitting increases significantly. Following the recent developments in inductive semantic stochastic methods, this paper studies the feasibility of using information gathered from the semantic neighborhood to decide when to stop the search. Two semantic stopping criteria are...

  7. Good news is bad news: Leverage cycles and sudden stops

    OpenAIRE

    Akinci, Ozge; Chahrour, Ryan

    2015-01-01

    We show that a model with imperfectly forecastable changes in future productivity and an occasionally binding collateral constraint can match a set of stylized facts about “sudden stop” events. “Good” news about future productivity raises leverage during times of expansion, increasing the probability that the constraint binds, and a sudden stop occurs, in future periods. The economy exhibits a boom period in the run-up to the sudden stop, with output, consumption, and investment all above tre...

  8. Modeling Stop-and-Go Waves in Pedestrian Dynamics

    OpenAIRE

    Portz, Andrea; Seyfried, Armin

    2010-01-01

    Several spatially continuous pedestrian dynamics models have been validated against empirical data. We try to reproduce the experimental fundamental diagram (velocity versus density) with simulations. In addition to this quantitative criterion, we tried to reproduce stop-and-go waves as a qualitative criterion. Stop-and-go waves are a characteristic phenomenon for the single file movement. Only one of three investigated models satisfies both criteria.

  9. Benzimidazole -Resistance in Haemonchus Contortus: New PCR-RFLP Method for the Detection of Point Mutation at Codon 167 of Isotype 1 Β-Tubulin Gene

    Directory of Open Access Journals (Sweden)

    A Eslami

    2012-12-01

    Full Text Available Background: Due to the lack of a suitable and economic test for the analysis of the polymorphism at codon 167, we developed a new PCR-RFLP technique, based on a modified forward primer (UT-HC167 MF-primer, to identify simultaneously the SNPs at codons 167 and 200 of isotype 1 β-tubu­lin gene of Haemonchus contortus.Methods: There already are several safe and easy methods for identification of point mutations at codons 198 and 200. Due to the lack of a reliable and easy method for the detection of the single nucleo­tide polymorphism (SNP at codon 167, we developed an innovative PCR-RFLP technique based on a modified forward primer (UT-HC167 MF-primer, in which the nucleotide T at the posi­tion 443 was substituted through a nucleotide A creating a restriction site for restriction endonuc­lease SnaB I in the nucleotide sequences including codon 167. A total of 138 adult male H. contortus were collected from three different geo-climatic areas of Iran. The isolated genomic DNA of each single worm was amplified by PCR using primers flanking codon 167. The PCR product (527 bp was then amplified by semi-nested PCR using the UT-HC167 MF-primer and the reverse primer achiev­ing a PCR product of 451 bp in length. This PCR product was subsequently digested with the restriction endonucleases SnaB I and TaaI for analysis of the mutations at codons 167 and 200, respec­tively.Results: All worms had two alleles encoding for phenylalanine (BZss homozygote for both codons.Conclusion: Using the UT-HC167 MF-primer and a suitable reverse primer designed upstream from codon 200, it is possible to amplify a PCR product which can be used for analysis of the SNPs at all three mentioned codons using RFLP.

  10. RNA-ID, a highly sensitive and robust method to identify cis-regulatory sequences using superfolder GFP and a fluorescence-based assay.

    Science.gov (United States)

    Dean, Kimberly M; Grayhack, Elizabeth J

    2012-12-01

    We have developed a robust and sensitive method, called RNA-ID, to screen for cis-regulatory sequences in RNA using fluorescence-activated cell sorting (FACS) of yeast cells bearing a reporter in which expression of both superfolder green fluorescent protein (GFP) and yeast codon-optimized mCherry red fluorescent protein (RFP) is driven by the bidirectional GAL1,10 promoter. This method recapitulates previously reported progressive inhibition of translation mediated by increasing numbers of CGA codon pairs, and restoration of expression by introduction of a tRNA with an anticodon that base pairs exactly with the CGA codon. This method also reproduces effects of paromomycin and context on stop codon read-through. Five key features of this method contribute to its effectiveness as a selection for regulatory sequences: The system exhibits greater than a 250-fold dynamic range, a quantitative and dose-dependent response to known inhibitory sequences, exquisite resolution that allows nearly complete physical separation of distinct populations, and a reproducible signal between different cells transformed with the identical reporter, all of which are coupled with simple methods involving ligation-independent cloning, to create large libraries. Moreover, we provide evidence that there are sequences within a 9-nt library that cause reduced GFP fluorescence, suggesting that there are novel cis-regulatory sequences to be found even in this short sequence space. This method is widely applicable to the study of both RNA-mediated and codon-mediated effects on expression.

  11. Evolutionary rates at codon sites may be used to align sequences and infer protein domain function

    Directory of Open Access Journals (Sweden)

    Hazelhurst Scott

    2010-03-01

    Full Text Available Abstract Background Sequence alignments form part of many investigations in molecular biology, including the determination of phylogenetic relationships, the prediction of protein structure and function, and the measurement of evolutionary rates. However, to obtain meaningful results, a significant degree of sequence similarity is required to ensure that the alignments are accurate and the inferences correct. Limitations arise when sequence similarity is low, which is particularly problematic when working with fast-evolving genes, evolutionary distant taxa, genomes with nucleotide biases, and cases of convergent evolution. Results A novel approach was conceptualized to address the "low sequence similarity" alignment problem. We developed an alignment algorithm termed FIRE (Functional Inference using the Rates of Evolution, which aligns sequences using the evolutionary rate at codon sites, as measured by the dN/dS ratio, rather than nucleotide or amino acid residues. FIRE was used to test the hypotheses that evolutionary rates can be used to align sequences and that the alignments may be used to infer protein domain function. Using a range of test data, we found that aligning domains based on evolutionary rates was possible even when sequence similarity was very low (for example, antibody variable regions. Furthermore, the alignment has the potential to infer protein domain function, indicating that domains with similar functions are subject to similar evolutionary constraints. These data suggest that an evolutionary rate-based approach to sequence analysis (particularly when combined with structural data may be used to study cases of convergent evolution or when sequences have very low similarity. However, when aligning homologous gene sets with sequence similarity, FIRE did not perform as well as the best traditional alignment algorithms indicating that the conventional approach of aligning residues as opposed to evolutionary rates remains the

  12. Association between p53 codon 72 polymorphism and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Mohammad Nabavi

    2014-06-01

    Full Text Available Aim : Systemic lupus erythematosus (SLE is a systemic vasculitic disorder, with multiple genes involved in the disease pathogenesis. The p53 gene plays an important role in controlling the cell cycle. We aimed to study the prevalence of p53 polymorphism in SLE patients and analyze the relationship between the p53 polymorphism and clinical-laboratory features of the disease. Material and methods : This case-control study was conducted on patients with confirmed SLE at Namazi Hospital, Shiraz, Iran. Seventy-seven patients with SLE including 9 (11.8% men and 68 (88.2% women with mean age of 25.61 ±10.69 years and 80 healthy controls with mean age of 51.82 ±14.25 years were included. The patients’ information, including the epidemiological profile, disease history, disease symptoms and also the laboratory findings, were extracted from the hospital records. The p53 expression was determined in lyzed lymphocytes. The data were analyzed using SPSS software version 14.00 for Windows considering p < 0.05 as statistically significant. Results : The frequencies of Arg/Arg, Pro/Pro and Arg/Pro among normal controls were 38.8%, 28.8% and 37.5%, respectively, but in the patients, Arg/Arg, Pro/Pro and Arg/Pro genotypes frequencies were shown to be 29.2%, 12.3% and 58.5%, respectively. Thus, heterozygous form of this polymorphism was shown to be associated with the disease more than the homozygous alleles. There was a significant relationship between the different allele types of p53 and some clinical features of SLE. There was no association between the different allele types and any of the initial manifestations of the disease and the laboratory findings, as well. Conclusions: In an Iranian population the functional oncoprotein of p53 with codon 72 polymorphism may play an important role in the pathogenesis and clinical presentation of SLE.

  13. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K.C.; Qiu, Jian-Wen

    2017-01-01

    responses of two congeneric snails to various hypoxic conditions, as well as codon substitution analysis at transcriptomic level to detect signals of positive selection in hypoxia-responsive genes. The integrated physiological, proteomic and transcriptomic approach can be applied in other non-model species to understand the molecular mechanisms of adaptation to global environmental change.

  14. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    responses of two congeneric snails to various hypoxic conditions, as well as codon substitution analysis at transcriptomic level to detect signals of positive selection in hypoxia-responsive genes. The integrated physiological, proteomic and transcriptomic approach can be applied in other non-model species to understand the molecular mechanisms of adaptation to global environmental change.

  15. The frequentist implications of optional stopping on Bayesian hypothesis tests.

    Science.gov (United States)

    Sanborn, Adam N; Hills, Thomas T

    2014-04-01

    Null hypothesis significance testing (NHST) is the most commonly used statistical methodology in psychology. The probability of achieving a value as extreme or more extreme than the statistic obtained from the data is evaluated, and if it is low enough, the null hypothesis is rejected. However, because common experimental practice often clashes with the assumptions underlying NHST, these calculated probabilities are often incorrect. Most commonly, experimenters use tests that assume that sample sizes are fixed in advance of data collection but then use the data to determine when to stop; in the limit, experimenters can use data monitoring to guarantee that the null hypothesis will be rejected. Bayesian hypothesis testing (BHT) provides a solution to these ills because the stopping rule used is irrelevant to the calculation of a Bayes factor. In addition, there are strong mathematical guarantees on the frequentist properties of BHT that are comforting for researchers concerned that stopping rules could influence the Bayes factors produced. Here, we show that these guaranteed bounds have limited scope and often do not apply in psychological research. Specifically, we quantitatively demonstrate the impact of optional stopping on the resulting Bayes factors in two common situations: (1) when the truth is a combination of the hypotheses, such as in a heterogeneous population, and (2) when a hypothesis is composite-taking multiple parameter values-such as the alternative hypothesis in a t-test. We found that, for these situations, while the Bayesian interpretation remains correct regardless of the stopping rule used, the choice of stopping rule can, in some situations, greatly increase the chance of experimenters finding evidence in the direction they desire. We suggest ways to control these frequentist implications of stopping rules on BHT.

  16. Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sigal, R.J.; Doria, A.; Warram, J.H.; Krolewski, A.S. [Joslin Diabetes Center, Boston, MA (United States)

    1996-04-01

    Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-AGG single base substitution (corresponding to a glycine-arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG{r_arrow}AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases ({approximately}3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight. 9 refs., 2 tabs.

  17. Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

    Science.gov (United States)

    Larocca, Nancy; Moreno, Dolores; Garmendia, Jenny Valentina; Velasquez, Olga; Martin-Rojo, Joana; Talamo, Carlos; Garcia, Alexis; De Sanctis, Juan Bautista

    2013-12-01

    One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

  18. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634

    Directory of Open Access Journals (Sweden)

    Ješić Maja D.

    2014-01-01

    Full Text Available Introduction. The multiple endocrine neoplasia type 2A (MEN 2A syndrome, comprising medullary thyroid carcinoma (MTC, pheochromocytoma and primary hyperparathyroidism (PHPT is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy’s father and grandmother and paternal aunt in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml, has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  19. SCREENING FOR GENETIC CHANGES AND CODON 129 POLYMORPHISM IN PRNP GENE IN HEALTHY SLOVENIAN POPULATION AND SPORADIC CASES OF CREUTZFELDT-JAKOB DISEASE

    Directory of Open Access Journals (Sweden)

    Sava Smerkolj

    2004-11-01

    Full Text Available Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD. Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes.Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer.Results. Methionine homozygotes comprised 46.8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%, 1 was valine homozygote (8.3% and 1 was heterozygote (8.3%.Found SNPs were combination of codon 76 change (228C > T and codon 84 change (252T > C in a single sample of healthy population, combination of codon 68 change (204T > C and codon 76 change (228C > T in two samples of healthy population and codon 117 change (351A > G in a healthy population sample and in a valine homozygote patient.Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD, because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non-familial, sporadic disease form.

  20. Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

    Science.gov (United States)

    Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A

    2018-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

  1. Prion protein with Y145STOP mutation induces mitochondria-mediated apoptosis and PrP-containing deposits in vitro

    International Nuclear Information System (INIS)

    Hachiya, Naomi S.; Watanabe, Kota; Kawabata, Makiko Y.; Jozuka, Akiko; Kozuka, Yoshimichi; Sakasegawa, Yuji; Kaneko, Kiyotoshi

    2005-01-01

    A pathogenic truncation of an amber mutation at codon 145 (Y145STOP) in Gerstmann-Straussler-Scheinker disease (GSS) was investigated through the real-time imaging in living cells, by utilizing GFP-PrP constructs. GFP-PrP(1-144) exhibited an aberrant localization to mitochondria in mouse neuroblastoma neuro2a (N2a) and HpL3-4 cells, a hippocampal cell line established from prnp gene-ablated mice, whereas full-length GFP-PrP did not. The aberrant mitochondrial localization was also confirmed by Western blot analysis. Since GFP-PrP(1-121), as previously reported, and full-length GFP-PrP do not exhibit such mitochondrial localization, the mitochondrial localization of GFP-PrP(1-144) requires not only PrP residues 121-144 (in human sequence) but also COOH-terminal truncation in the current experimental condition. Subsequently, the GFP-PrP(1-144) induced a change in the mitochondrial innermembrane potential (ΔΨ m ), release of cytochrome c from the intermembrane space into the cytosol, and DNA fragmentation in these cells. Non-fluorescent PrP(1-144) also induced the DNA fragmentation in N2a and HpL3-4 cells after the proteasomal inhibition. These data may provide clues as to the molecular mechanism of the neurotoxic property of Y145STOP mutation. Furthermore, immunoelectron microscopy revealed numerous electron-dense deposits in mitochondria clusters of GFP-PrP(1-144)-transfected N2a cells, whereas no deposit was detected in the cells transfected with full-length GFP-PrP. Co-localization of GFP/PrP-immunogold particles with porin-immunogold particles as a mitochondrial marker was observed in such electron-dense vesicular foci, resembling those found in autophagic vacuoles forming secondary lysosomes. Whether such electron-dense deposits may serve as a seed for the growth of amyloid plaques, a characteristic feature of GSS with Y145STOP, awaits further investigations

  2. Exploring the nearly degenerate stop region with sbottom decays

    Energy Technology Data Exchange (ETDEWEB)

    An, Haipeng [Walter Burke Institute for Theoretical Physics, California Institute of Technology,1200 E. California Blvd, Pasadena, CA, 91125 (United States); Gu, Jiayin [Center for Future High Energy Physics, Institute of High Energy Physics,19B YuquanLu, Chinese Academy of Sciences, Beijing, 100049 (China); DESY,Notkestraße 85, Hamburg, D-22607 (Germany); Wang, Lian-Tao [Enrico Fermi Institute, University of Chicago,5640 S Ellis Ave., Chicago, IL, 60637 (United States); Kavli Institute for Cosmological Physics, University of Chicago,5640 S Ellis Ave., Chicago, IL, 60637 (United States)

    2017-04-13

    A light stop with mass almost degenerate with the lightest neutralino has important connections with both naturalness and dark matter relic abundance. This region is also very hard to probe at colliders. In this paper, we demonstrate the potential of searching for such stop particles at the LHC from sbottom decays, focusing on two channels with final states 2ℓ+E{sub T}{sup miss} and 1b1ℓ+E{sub T}{sup miss}. We found that, if the lightest sbottom has mass around or below 1 TeV and has a significant branching ratio to decay to stop and W (b̃→t̃ W), a stop almost degenerate with neutralino can be excluded up to about 500–600 GeV at the 13 TeV LHC with 300 fb{sup −1} data. The searches we propose are complementary to other SUSY searches at the LHC and could have the best sensitivity to the stop-bino coannihilation region. Since they involve final states which have already been used in LHC searches, a reinterpretation of the search results already has sensitivity. Further optimization could deliver the full potential of these channels.

  3. Exploring the nearly degenerate stop region with sbottom decays

    Energy Technology Data Exchange (ETDEWEB)

    An, Haipeng [California Institute of Technology, Pasadena, CA (United States). Walter Burke Inst. for Theoretical Physics; Gu, Jiayin [Chinese Academy of Sciences, Beijing (China). Inst. of High Energy Physics; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Wang, Lian-Tao [Chicago Univ., IL (United States). Enrico Fermi Inst.; Chicago Univ., IL (United States). Kavli Inst. for Cosmological Physics

    2016-11-15

    A light stop with mass almost degenerate with the lightest neutralino has important connections with both naturalness and dark matter relic abundance. This region is also very hard to probe at colliders. In this paper, we demonstrate the potential of searching for such stop particles at the LHC from sbottom decays, focusing on two channels with final states 2l+E{sup miss}{sub T} and 1b1l+E{sup miss}{sub T}. We found that, if the lightest sbottom has mass around or below 1 TeV and has a significant branching ratio to decay to stop and W (b→tW), a stop almost degenerate with neutralino can be excluded up to about 500-600 GeV at the 13 TeV LHC with 300 fb{sup -1} data. The searches we propose are complementary to other SUSY searches at the LHC and could have the best sensitivity to the stop-bino coannihilation region. Since they involve final states which have already been used in LHC searches, a reinterpretation of the search results already has sensitivity. Further optimization could deliver the full potential of these channels.

  4. Stopping time of a one-dimensional bounded quantum walk

    International Nuclear Information System (INIS)

    Luo Hao; Zhang Peng; Zhan Xiang; Xue Peng

    2016-01-01

    The stopping time of a one-dimensional bounded classical random walk (RW) is defined as the number of steps taken by a random walker to arrive at a fixed boundary for the first time. A quantum walk (QW) is a non-trivial generalization of RW, and has attracted a great deal of interest from researchers working in quantum physics and quantum information. In this paper, we develop a method to calculate the stopping time for a one-dimensional QW. Using our method, we further compare the properties of stopping time for QW and RW. We find that the mean value of the stopping time is the same for both of these problems. However, for short times, the probability for a walker performing a QW to arrive at the boundary is larger than that for a RW. This means that, although the mean stopping time of a quantum and classical walker are the same, the quantum walker has a greater probability of arriving at the boundary earlier than the classical walker. (paper)

  5. Reciprocity in the electronic stopping of slow ions in matter

    International Nuclear Information System (INIS)

    Sigmund, P.

    2008-01-01

    The principle of reciprocity, i.e., the invariance of the inelastic excitation in ion-atom collisions against interchange of projectile and target, has been applied to the electronic stopping cross section of low-velocity ions and tested empirically on ion-target combinations supported by a more or less adequate amount of experimental data. Reciprocity is well obeyed (within ∼10%) for many systems studied, and deviations exceeding ∼20% are exceptional. Systematic deviations such as gas-solid or metal-insulator differences have been looked for but not identified on the present basis. A direct consequence of reciprocity is the equivalence of Z 1 with Z 2 structure for random slowing down. This feature is reasonably well supported empirically for ion-target combinations involving carbon, nitrogen, aluminium and argon. Reciprocity may be utilized as a criterion to reject questionable experimental data. In cases where a certain stopping cross section has not been or cannot be measured, the stopping cross section for the inverted system may be available and serve as a first estimate. It is suggested to build in reciprocity as a fundamental requirement into empirical interpolation schemes directed at the stopping of low-velocity ions. Examination of the SRIM and MSTAR codes reveals cases where reciprocity is obeyed accurately, but deviations of up to a factor of two are common. In case of heavy ions such as gold, electronic stopping cross sections predicted by SRIM are asserted to be almost an order of magnitude too high. (authors)

  6. Simulation on effect of stopping nuclear power generation

    International Nuclear Information System (INIS)

    Yajima, Masayuki; Kumakura, Osamu; Sakurai, Norihisa; Nagata, Yutaka; Hattori, Tsuneaki

    1990-01-01

    The effects that the stopping of nuclear power generation exerts on the price of primary energy such as petroleum, LNG and coal and the trend of Japanese energy and economy are analyzed by using the medium term economy forecasting system. In the simulation, the case of stopping nuclear power generation in seven countries of OECD is supposed, and as for the process of stopping, two cases of immediate stopping and stopping by gradual reduction are set up. The models used for the simulation are the world energy model, the competition among energies model and the multiple category model. By the decrease of nuclear power generation, thermal power generation increases, and the demand of fossil fuel increases. As the result, the price of fossil fuel rises (the world energy model), and the price of fossil fuel imported to Japan rises. Also the quantity of fossil fuel import to Japan increase. These price rise and quantity increase exert deflation effect to Japanese economy (the multiple category model). The price rise of fossil fuel affects the competition among energies in Japan through the relative change of secondary energy price (the competition among energies model). The impact to the world and to Japan is discussed. (K.I.)

  7. Reciprocity in the electronic stopping of slow ions in matter

    Science.gov (United States)

    Sigmund, P.

    2008-04-01

    The principle of reciprocity, i.e., the invariance of the inelastic excitation in ion-atom collisions against interchange of projectile and target, has been applied to the electronic stopping cross section of low-velocity ions and tested empirically on ion-target combinations supported by a more or less adequate amount of experimental data. Reciprocity is well obeyed (within ~10%) for many systems studied, and deviations exceeding ~20% are exceptional. Systematic deviations such as gas-solid or metal-insulator differences have been looked for but not identified on the present basis. A direct consequence of reciprocity is the equivalence of Z1 with Z2 structure for random slowing down. This feature is reasonably well supported empirically for ion-target combinations involving carbon, nitrogen, aluminium and argon. Reciprocity may be utilized as a criterion to reject questionable experimental data. In cases where a certain stopping cross section has not been or cannot be measured, the stopping cross section for the inverted system may be available and serve as a first estimate. It is suggested to build in reciprocity as a fundamental requirement into empirical interpolation schemes directed at the stopping of low-velocity ions. Examination of the SRIM and MSTAR codes reveals cases where reciprocity is obeyed accurately, but deviations of up to a factor of two are common. In case of heavy ions such as gold, electronic stopping cross sections predicted by SRIM are asserted to be almost an order of magnitude too high.

  8. Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions.

    Science.gov (United States)

    Subramanian, Abhishek; Sarkar, Ram Rup

    2015-10-01

    Understanding the variations in gene organization and its effect on the phenotype across different Leishmania species, and to study differential clinical manifestations of parasite within the host, we performed large scale analysis of codon usage patterns between Leishmania and other known Trypanosomatid species. We present the causes and consequences of codon usage bias in Leishmania genomes with respect to mutational pressure, translational selection and amino acid composition bias. We establish GC bias at wobble position that governs codon usage bias across Leishmania species, rather than amino acid composition bias. We found that, within Leishmania, homogenous codon context coding for less frequent amino acid pairs and codons avoiding formation of folding structures in mRNA are essentially chosen. We predicted putative differences in global expression between genes belonging to specific pathways across Leishmania. This explains the role of evolution in shaping the otherwise conserved genome to demonstrate species-specific function-level differences for efficient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Codon and amino acid usage in two major human pathogens of genus Bartonella--optimization between replicational-transcriptional selection, translational control and cost minimization.

    Science.gov (United States)

    Das, Sabyasachi; Paul, Sandip; Chatterjee, Sanjib; Dutta, Chitra

    2005-01-01

    Intra-genomic variation in synonymous codon and amino acid usage in two human pathogens Bartonella henselae and B. quintana has been carried out through multivariate analysis. Asymmetric mutational bias, coupled with replicational-transcriptional selection, has been identified as the prime selection force behind synonymous codon selection--a characteristic of the genus Bartonella, not exhibited by any other alpha-proteobacterial genome. Distinct codon usage patterns and low synonymous divergence values between orthologous sequences of highly expressed genes from the two Bartonella species indicate that there exists a residual intra-strand synonymous codon bias in the highly expressed genes, possibly operating at the level of translation. In the case of amino acid usage, the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact, while strand-specific mutational pressure and gene expressivity strongly influence the inter-strand variations. In both species under study, the highly expressed gene products tend not to contain heavy and/or aromatic residues, following the cost-minimization hypothesis in spite of their intracellular lifestyle. The codon and amino acid usage in these two human pathogens are, therefore, consequences of a complex balance between replicational-transcriptional selection, translational control, protein hydropathy and cost minimization.

  10. Stopping and energy deposition of hadrons in target nuclei

    International Nuclear Information System (INIS)

    Strugalski, Z.

    1983-01-01

    In an analysis of pion-xenon nucleus collisions at 2.34-9 GeV/c momentum events are identified in which incident pions were completely stopped and deposited their energy in target nucleus. Probability of appearance of such ''stopped'' events among any-type pion-xenon collision events depends on the incident pion momentum and is: approximately 0.15 at 2.34 GeV/c, approximately 0.02 at 3.5 GeV/c, and approximately 0 at higher momenta. Formula expressing probability of appearance of the ''stopped'' events is derived. Range-energy relation in nuclear matter for pions and protons is given

  11. Proposal for a CINDA-type stopping data bibliography (CISDA)

    International Nuclear Information System (INIS)

    Ivascu, M.; Bucurescu, D.; Avrigeanu, V.

    1980-11-01

    The present status and requirements of stopping power data (SD) are reviewed, by considering the significant trends in applications of nuclear data. The need of centralized information on SD is emphasized. If the establishing of compiled and evaluated SD libraries format is possible only through an internationally co-ordinated action, to produce a computerized index to bibliographic references on SD is an easier task. One describes a plan of a CINDA-type SD bibliography (named CISDA - Computer Index of Stopping Data) containing experimental, theoretical and evaluated works for stopping powers, range, energy and range straggling of ions with atomic mass and charge both larger than or equal to 1. The index organization and detailed field descriptions of reference records are presented. (author)

  12. New developments in stopping power for fast ions

    International Nuclear Information System (INIS)

    Paul, Helmut

    2007-01-01

    We discuss the available stopping power tables and codes, and new experimental methods. Among the semi-empirical stopping power tables, SRIM and MSTAR describe experimental data best. Of the recent theoretical stopping codes CasP, PASS, TCS and dielectric formalism, all describe some data well. PASS is the only theoretical code with an extended table for many ions and targets, but on the average, its predictive value at low energies is less than that of SRIM or MSTAR. The first-principle extended classical trajectory Monte Carlo method is very promising. The ToF-E ERDA arrangements have made it possible to produce accurate data for many ion-target combinations. A new liquid jet target method promises data for liquid water which is an important substance for medical dosimetry

  13. Ball Screw Actuator Including a Compliant Ball Screw Stop

    Science.gov (United States)

    Wingett, Paul T. (Inventor); Hanlon, Casey (Inventor)

    2017-01-01

    An actuator includes a ball nut, a ball screw, and a ball screw stop. The ball nut is adapted to receive an input torque and in response rotates and supplies a drive force. The ball screw extends through the ball nut and has a first end and a second end. The ball screw receives the drive force from the ball nut and in response selectively translates between a retract position and a extend position. The ball screw stop is mounted on the ball screw proximate the first end to translate therewith. The ball screw stop engages the ball nut when the ball screw is in the extend position, translates, with compliance, a predetermined distance toward the first end upon engaging the ball nut, and prevents further rotation of the ball screw upon translating the predetermined distance.

  14. Ball Screw Actuator Including an Axial Soft Stop

    Science.gov (United States)

    Wingett, Paul T. (Inventor); Forrest, Steven Talbert (Inventor); Abel, Steve (Inventor); Woessner, George (Inventor); Hanlon, Casey (Inventor)

    2016-01-01

    An actuator includes an actuator housing, a ball screw, and an axial soft stop assembly. The ball screw extends through the actuator housing and has a first end and a second end. The ball screw is coupled to receive a drive force and is configured, upon receipt of the drive force, to selectively move in a retract direction and an extend direction. The axial soft stop assembly is disposed within the actuator housing. The axial soft stop assembly is configured to be selectively engaged by the ball screw and, upon being engaged thereby, to translate, with compliance, a predetermined distance in the extend direction, and to prevent further movement of the ball screw upon translating the predetermined distance.

  15. Why do People Stop Playing On-Line Games?

    DEFF Research Database (Denmark)

    Sudzina, Frantisek; Razmerita, Liana

    2012-01-01

    The recent initial public offering of shares of Zynga, probably the most important on-line game provider, drew interest of potential investors but also of general public to their business model. What the most interested people learned so far is that if Zynga had not changed their accounting...... practice, they would be in red numbers for several months already. This is most likely caused by people stopping to play their games. This paper provides an estimate of what proportion of people, who played on-line games, already stopped playing them. Additionally, it analyzed the reasons why people...... stopped playing on-line games. It also compares Facebook and other on-line games....

  16. Fricative-stop coarticulation: acoustic and perceptual evidence.

    Science.gov (United States)

    Repp, B H; Mann, V A

    1982-06-01

    Eight native speakers of American English each produced ten tokens of all possible CV, FCV, and VFCV utterances with V = [a] or [u], F = [s] or [integral of], and C = [t] or [k]. Acoustic analysis showed that the formant transition onsets following the stop consonant release were systematically influenced by the preceding fricative, although there were large individual differences. In particular, F3 and F4 tended to be higher following [s] than following [integral of]. The coarticulatory effects were equally large in FCV (e.g.,/sta/) and VFCV (e.g.,/asda/) utterances; that is, they were not reduced when a syllable boundary intervened between fricative and stop. In a parallel perceptual study, the CV portions of these utterances (with release bursts removed to provoke errors) were presented to listeners for identification of the stop consonant. The pattern of place-of-articulation confusions, too, revealed coarticulatory effects due to the excised fricative context.

  17. Companion classroom activities for "stop faking it!" force and motion

    CERN Document Server

    Robertson, William C

    2011-01-01

    Never has it been so easy for educators to learn to teach physical science with confidence. Award-winning author Bill Robertson launched his bestselling Stop Faking It! series in 2002 with Force and Motion--offering elementary and middle school teachers a jargon-free way to learn the background for teaching physical science with confidence. Combining easy-to-understand if irreverent explanations and quirky diagrams, Stop Faking It! Force and Motion helped thousands of teachers, parents, and homeschoolers conquer topics from Newton s laws to the physics of space travel. Now Companion Classroom Activities for Stop Faking It! Force and Motion proves an ideal supplement to the original book or a valuable resource of its own. The hands-on activities and highly readable explanations allow students to first investigate concepts, then discuss learned concepts, and finally apply the concepts to everyday situations. Robertson's wit and humor are sure to keep students and teachers entertained while they tackle topics ...

  18. 49 CFR 392.22 - Emergency signals; stopped commercial motor vehicles.

    Science.gov (United States)

    2010-10-01

    ... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Stopped Commercial Motor Vehicles § 392.22 Emergency signals; stopped commercial motor vehicles. (a) Hazard warning signal flashers. Whenever a commercial motor vehicle... than necessary traffic stops, the driver of the stopped commercial motor vehicle shall immediately...

  19. Can I Stop Myself From Having a Wet Dream? (For Teens)

    Science.gov (United States)

    ... Can I Stop Myself From Having a Wet Dream? KidsHealth / For Teens / Can I Stop Myself From Having a Wet Dream? Print Can I stop myself from having a wet dream? – Tom* You really can't stop wet dreams, ...

  20. Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

    Science.gov (United States)

    Rivu, Sanzana Fareen; Apu, Mohd Nazmul Hasan; Shabnaz, Samia; Nahid, Noor Ahmed; Islam, Md Reazul; Al-Mamun, Mir Md Abdullah; Nahar, Zabun; Rabbi, Sikder Nahidul Islam; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul

    2017-08-01

    Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160Ccolorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, pcolorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (pcolorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, pcolorectal cancer development in Bangladeshi population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Codon Optimization Significantly Improves the Expression Level of α-Amylase Gene from Bacillus licheniformis in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Jian-Rong Wang

    2015-01-01

    Full Text Available α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis, the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use.

  2. Transgenic rice expressing a codon-modified synthetic CP4-EPSPS confers tolerance to broad-spectrum herbicide, glyphosate.

    Science.gov (United States)

    Chhapekar, Sushil; Raghavendrarao, Sanagala; Pavan, Gadamchetty; Ramakrishna, Chopperla; Singh, Vivek Kumar; Phanindra, Mullapudi Lakshmi Venkata; Dhandapani, Gurusamy; Sreevathsa, Rohini; Ananda Kumar, Polumetla

    2015-05-01

    Highly tolerant herbicide-resistant transgenic rice was developed by expressing codon-modified synthetic CP4--EPSPS. The transformants could tolerate up to 1% commercial glyphosate and has the potential to be used for DSR (direct-seeded rice). Weed infestation is one of the major biotic stress factors that is responsible for yield loss in direct-seeded rice (DSR). Herbicide-resistant rice has potential to improve the efficiency of weed management under DSR. Hence, the popular indica rice cultivar IR64, was genetically modified using Agrobacterium-mediated transformation with a codon-optimized CP4-EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, with N-terminal chloroplast targeting peptide from Petunia hybrida. Integration of the transgenes in the selected rice plants was confirmed by Southern hybridization and expression by Northern and herbicide tolerance assays. Transgenic plants showed EPSPS enzyme activity even at high concentrations of glyphosate, compared to untransformed control plants. T0, T1 and T2 lines were tested by herbicide bioassay and it was confirmed that the transgenic rice could tolerate up to 1% of commercial Roundup, which is five times more in dose used to kill weeds under field condition. All together, the transgenic rice plants developed in the present study could be used efficiently to overcome weed menace.

  3. A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria

    Directory of Open Access Journals (Sweden)

    Farias Fabiana HG

    2012-07-01

    Full Text Available Abstract Background L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia. Case presentation Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional. Conclusions We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

  4. [Correlation of codon biases and potential secondary structures with mRNA translation efficiency in unicellular organisms].

    Science.gov (United States)

    Vladimirov, N V; Likhoshvaĭ, V A; Matushkin, Iu G

    2007-01-01

    Gene expression is known to correlate with degree of codon bias in many unicellular organisms. However, such correlation is absent in some organisms. Recently we demonstrated that inverted complementary repeats within coding DNA sequence must be considered for proper estimation of translation efficiency, since they may form secondary structures that obstruct ribosome movement. We have developed a program for estimation of potential coding DNA sequence expression in defined unicellular organism using its genome sequence. The program computes elongation efficiency index. Computation is based on estimation of coding DNA sequence elongation efficiency, taking into account three key factors: codon bias, average number of inverted complementary repeats, and free energy of potential stem-loop structures formed by the repeats. The influence of these factors on translation is numerically estimated. An optimal proportion of these factors is computed for each organism individually. Quantitative translational characteristics of 384 unicellular organisms (351 bacteria, 28 archaea, 5 eukaryota) have been computed using their annotated genomes from NCBI GenBank. Five potential evolutionary strategies of translational optimization have been determined among studied organisms. A considerable difference of preferred translational strategies between Bacteria and Archaea has been revealed. Significant correlations between elongation efficiency index and gene expression levels have been shown for two organisms (S. cerevisiae and H. pylori) using available microarray data. The proposed method allows to estimate numerically the coding DNA sequence translation efficiency and to optimize nucleotide composition of heterologous genes in unicellular organisms. http://www.mgs.bionet.nsc.ru/mgs/programs/eei-calculator/.

  5. ANCAC: amino acid, nucleotide, and codon analysis of COGs--a tool for sequence bias analysis in microbial orthologs.

    Science.gov (United States)

    Meiler, Arno; Klinger, Claudia; Kaufmann, Michael

    2012-09-08

    The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC's NUCOCOG dataset as the largest one available for that purpose thus far. Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills.

  6. ANCAC: amino acid, nucleotide, and codon analysis of COGs – a tool for sequence bias analysis in microbial orthologs

    Directory of Open Access Journals (Sweden)

    Meiler Arno

    2012-09-01

    Full Text Available Abstract Background The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Results Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC’s NUCOCOG dataset as the largest one available for that purpose thus far. Conclusions Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills.

  7. ANCAC: amino acid, nucleotide, and codon analysis of COGs – a tool for sequence bias analysis in microbial orthologs

    Science.gov (United States)

    2012-01-01

    Background The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Results Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC’s NUCOCOG dataset as the largest one available for that purpose thus far. Conclusions Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills. PMID:22958836

  8. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

    Science.gov (United States)

    BANERJI, JULIAN

    2015-01-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

  9. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

    Science.gov (United States)

    Banerji, Julian

    2015-09-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

  10. One-stop endoscopic hernia surgery: efficient and satisfactory.

    Science.gov (United States)

    Voorbrood, C E H; Burgmans, J P J; Clevers, G J; Davids, P H P; Verleisdonk, E J M M; Schouten, N; van Dalen, T

    2015-06-01

    One-stop surgery offers patients diagnostic work-up and subsequent surgical treatment on the same day. In the present study, patient satisfaction and efficiency from an institutional perspective were evaluated in patients who were referred for one-stop endoscopic inguinal hernia repair. In a high-volume inguinal hernia clinic, all consecutive patients referred for one-stop surgical treatment, were registered prospectively. An instructed secretary screened patients for eligibility for the one-stop option when the appointment was made. Totally extraperitoneal hernia repair under general anaesthesia was the preferred operative technique. Patient's satisfaction, successful day surgery and institutional efficiency were evaluated. Between January 2010 and January 2012 a total of 349 patients (17 % of all patients in the hernia clinic) were referred for one-stop hernia repair. Mean age was 47.5 years and 96.3 % were males. Three hundred thirty-six patients underwent hernia surgery on the same day (96.3 %). In thirteen patients (3.7 %) no operative repair was done on the day of presentation due to an incorrect diagnosis (n = 7), a watchful waiting policy for asymptomatic hernia (n = 3), rescheduling due to a large scrotal hernia, and there were two "no shows". Following hernia repair 97 % of the patients were discharged on the same day, while ten patients required hospitalization. Based on the questionnaires the main satisfaction score among patients was 9.0 (8.89-9.17 95 % CI) on a scale ranging from 0 to 10. One-stop hernia surgery is feasible and satisfactory from an institutional as well as from a patient's perspective.

  11. A Conceptual Approach for Optimising Bus Stop Spacing

    Science.gov (United States)

    Johar, Amita; Jain, S. S.; Garg, P. k.

    2017-06-01

    An efficient public transportation system is essential of any country. The growth, development and shape of the urban areas are mainly due to availability of good transportation (Shah et al. in Inst Town Plan India J 5(3):50-59, 1). In developing countries, like India, travel by local bus in a city is very common. The accidents, congestion, pollution and appropriate location of bus stops are the major problems arising in metropolitan cities. Among all the metropolitan cities in India, Delhi has highest percentage of growth of population and vehicles. Therefore, it is important to adopt efficient and effective ways to improve mobility in different metropolitan cities in order to overcome the problem and to reduce the number of private vehicles on the road. The primary objective of this paper is to present a methodology for developing a model for optimum bus stop spacing (OBSS). It describes the evaluation of existing urban bus route, data collection, development of model for optimizing urban bus route and application of model. In this work, the bus passenger generalized cost method is used to optimize the spacing between bus stops. For the development of model, a computer program is required to be written. The applicability of the model has been evaluated by taking the data of urban bus route of Delhi Transport Corporation (DTC) in Excel sheet in first phase. Later on, it is proposed to develop a programming in C++ language. The developed model is expected to be useful to transport planner for rational design of the spacing of bus stops to save travel time and to generalize operating cost. After analysis it is found that spacing between the bus stop comes out to be between 250 and 500 m. The Proposed Spacing of bus stops is done considering the points that they don't come nearer to metro/rail station, entry or exit of flyover and near traffic signal.

  12. Light stops and fine-tuning in MSSM

    Energy Technology Data Exchange (ETDEWEB)

    Cici, Ali; Kirca, Zerrin; Uen, Cem Salih [Uludag Univ., Department of Physics, Bursa (Turkey)

    2018-01-15

    We discuss the fine-tuning issue within the MSSM framework. Following the idea that the fine-tuning can measure effects of some missing mechanism, we impose non-universal gaugino masses at the GUT scale, and explore the low scale implications. We realize that the fine-tuning parametrized with Δ{sub EW} can be as low as zero. We consider the stop mass with a special importance and focus on the mass scales as m{sub t} ≤ 700 GeV, which are excluded by the current experiments when the stop decays into a neutralino along with a top quark or a chargino along with a bottom quark. We find that the stop mass can be as low as about 250 GeV with Δ{sub EW} ∝ 50. We find that the solutions in this region can be excluded only up to 60% when stop decays into a neutralino-top quark, and 50% when it decays into a chargino-b quark. Setting 65% CL to be potential exclusion and 95% to be pure exclusion limit such solutions will be tested in near future experiments, which are conducted with higher luminosity. In addition to stop, the region with low fine-tuning and light stops predicts masses for the other supersymmetric particles such as m{sub b} >or similar 700 GeV, m{sub τ} >or similar 1 TeV, m{sub χ{sub 1}{sup {sub ±}}} >or similar 120 GeV. The details for the mass scales and decay rates are also provided by tables of benchmark points. (orig.)

  13. Light stops and fine-tuning in MSSM

    Science.gov (United States)

    Çiçi, Ali; Kırca, Zerrin; Ün, Cem Salih

    2018-01-01

    We discuss the fine-tuning issue within the MSSM framework. Following the idea that the fine-tuning can measure effects of some missing mechanism, we impose non-universal gaugino masses at the GUT scale, and explore the low scale implications. We realize that the fine-tuning parametrized with Δ _{EW} can be as low as zero. We consider the stop mass with a special importance and focus on the mass scales as m_{\\tilde{t}} ≤ 700 GeV, which are excluded by the current experiments when the stop decays into a neutralino along with a top quark or a chargino along with a bottom quark. We find that the stop mass can be as low as about 250 GeV with Δ _{EW} ˜ 50. We find that the solutions in this region can be exluded only up to 60% when stop decays into a neutralino-top quark, and 50% when it decays into a chargino-b quark. Setting 65% CL to be potential exclusion and 95% to be pure exclusion limit such solutions will be tested in near future experiments, which are conducted with higher luminosity. In addition to stop, the region with low fine-tuning and light stops predicts masses for the other supersymmetric particles such as m_{\\tilde{b}} ≳ 700 GeV, m_{\\tilde{τ }} ≳ 1 TeV, m_{\\tilde{χ }1^{± }} ≳ 120 GeV. The details for the mass scales and decay rates are also provided by tables of benchmark points.

  14. International Symposium of Scientists for Nuclear test Stopping

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    Problems discussed at International Symposium of Scientists for Nuclear Test Stopping in July 1986 in Moscow were considered. Scientists discussed complex of possible measures directed at strengthening of peace supporting mechanism, spoke in support of prohibition of all nuclear weapon tests. Necessity of measures preventing the weapon delivery to space, construction of the regime of using cosmic equipment exclusively for peace was noted. Attention was paid to the problem of control for test stopping (by means of sattelites and seismic methods), cooperation establishment between the USSR Academy of Sciences and the Council for the protection of the USA Natural Resources

  15. Anatomy of maximal stop mixing in the MSSM

    International Nuclear Information System (INIS)

    Bruemmer, Felix; Kraml, Sabine; Kulkarni, Suchita

    2012-05-01

    A Standard Model-like Higgs near 125 GeV in the MSSM requires multi-TeV stop masses, or a near-maximal contribution to its mass from stop mixing. We investigate the maximal mixing scenario, and in particular its prospects for being realized it in potentially realistic GUT models. We work out constraints on the possible GUT-scale soft terms, which we compare with what can be obtained from some well-known mechanisms of SUSY breaking mediation. Finally, we analyze two promising scenarios in detail, namely gaugino mediation and gravity mediation with non-universal Higgs masses.

  16. Anatomy of maximal stop mixing in the MSSM

    Energy Technology Data Exchange (ETDEWEB)

    Bruemmer, Felix [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kraml, Sabine; Kulkarni, Suchita [CNRS/IN2P3, INPG, Grenoble (France). Laboratoire de Physique Subatomique et de Cosmologie

    2012-05-15

    A Standard Model-like Higgs near 125 GeV in the MSSM requires multi-TeV stop masses, or a near-maximal contribution to its mass from stop mixing. We investigate the maximal mixing scenario, and in particular its prospects for being realized it in potentially realistic GUT models. We work out constraints on the possible GUT-scale soft terms, which we compare with what can be obtained from some well-known mechanisms of SUSY breaking mediation. Finally, we analyze two promising scenarios in detail, namely gaugino mediation and gravity mediation with non-universal Higgs masses.

  17. Summary the race to reinvent energy and stop global warming

    CERN Document Server

    2013-01-01

    Complete summary of Fred Krupp and Miriam Horn's book: ""Earth: The Sequel: The Race to Reinvent Energy and Stop Global Warming"". This summary of the ideas from Fred Krupp and Miriam Horn's book ""Earth: The Sequel"" explains how capitalism, as the most powerful economic force in the world, is the only engine of change that has the strength to stop global warming. In their book, the authors demonstrate how this can be achieved by installing a cap-and-trade initiative, providing genuine economic incentives for companies and reducing their carbon footprint. This summary explains their theory in

  18. Maintenance cost savings - snubber elimination with limit stops

    International Nuclear Information System (INIS)

    Monette, P.; Baltus, R.; Cloud, R.L.

    1995-01-01

    ''Active'' snubbers can be replaced with ''passive'' Limit Stops using two separate strategies. One is a straightforward piping re-analysis to optimize the number of dynamics supports and replace remaining snubbers with Limit Stops. A second approach is to take implicit advantage of the margins afforded by the ASME Code Case N-411 damping ratios and simply replace snubbers one-for-one with no re-analysis. Both methods result in major maintenance cost savings and both have been received favorably by the USNRC (United States Nuclear Regulatory Commission). Approaches to maintenance cost reduction using these strategies are discussed in this paper. (Author). 11 refs., 4 figs

  19. Maintenance cost savings - snubber elimination with limit stops

    International Nuclear Information System (INIS)

    Cloud, R.L.; Taylor, W.H.

    1993-01-01

    'Active' snubbers can be replaced with 'passive' Limit Stops using two separate strategies. One is a straightforward piping re-analysis to optimize the number of dynamic supports and replace remaining snubbers with Limit Stops. A second approach is to take implicit advantage of the margins afforded by the ASME Code Case N-411 reduced damping ratios and simply replace snubbers one-for-one with no re-analysis. Both methods result in major maintenance cost savings and both have been discussed with the NRC. Approaches to maintenance cost reduction using these strategies are discussed in this paper

  20. The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa

    OpenAIRE

    Benke, Amalia; Williams, Alford Joseph; MacNeil, Adam

    2017-01-01

    The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and sur...

  1. Over Expression of a tRNALeu Isoacceptor Changes Charging Pattern of Leucine tRNAs and Reveals New Codon Reading

    DEFF Research Database (Denmark)

    Sørensen, Michael Askvad; Elf, J.; Bouakaz, E.

    2005-01-01

    During mRNA translation, synonymous codons for one amino acid are often read by different isoaccepting tRNAs. The theory of selective tRNA charging predicts greatly varying percentages of aminoacylation among isoacceptors in cells starved for their common amino acid. It also predicts major changes...... in tRNA charging patterns upon concentration changes of single isoacceptors, which suggests a novel type of translational control of gene expression. We therefore tested the theory by measuring with Northern blots the charging of Leu-tRNAs in Escherichia coli under Leu limitation in response to over...... postulated a previously unknown common codon for tRNALeu GAG and tRNALeu UAG. Subsequently, we demonstrated that the tRNALeu GAG codon CUU is, in fact, read also by tRNALeu UAG, due to a uridine-5-oxyacetic acid modification....

  2. Analysis of phylogeny and codon usage bias and relationship of GC content, amino acid composition with expression of the structural nif genes.

    Science.gov (United States)

    Mondal, Sunil Kanti; Kundu, Sudip; Das, Rabindranath; Roy, Sujit

    2016-08-01

    Bacteria and archaea have evolved with the ability to fix atmospheric dinitrogen in the form of ammonia, catalyzed by the nitrogenase enzyme complex which comprises three structural genes nifK, nifD and nifH. The nifK and nifD encodes for the beta and alpha subunits, respectively, of component 1, while nifH encodes for component 2 of nitrogenase. Phylogeny based on nifDHK have indicated that Cyanobacteria is closer to Proteobacteria alpha and gamma but not supported by the tree based on 16SrRNA. The evolutionary ancestor for the different trees was also different. The GC1 and GC2% analysis showed more consistency than GC3% which appeared to below for Firmicutes, Cyanobacteria and Euarchaeota while highest in Proteobacteria beta and clearly showed the proportional effect on the codon usage with a few exceptions. Few genes from Firmicutes, Euryarchaeota, Proteobacteria alpha and delta were found under mutational pressure. These nif genes with low and high GC3% from different classes of organisms showed similar expected number of codons. Distribution of the genes and codons, based on codon usage demonstrated opposite pattern for different orientation of mirror plane when compared with each other. Overall our results provide a comprehensive analysis on the evolutionary relationship of the three structural nif genes, nifK, nifD and nifH, respectively, in the context of codon usage bias, GC content relationship and amino acid composition of the encoded proteins and exploration of crucial statistical method for the analysis of positive data with non-constant variance to identify the shape factors of codon adaptation index.

  3. Is one-stop surgery for carpal tunnel syndrome safe?

    DEFF Research Database (Denmark)

    Jørgensen, Louise Møller; Piil, Karin; Bashir, Asma

    2017-01-01

    OBJECTIVES: The aim of this study was to evaluate one-stop surgery (OSS) for carpal tunnel syndrome (CTS) regarding symptom relief and patient satisfaction. OSS in our setting means only one visit to the hospital for surgery and no hospital appointments for preassessment or follow-up. We hypothes...

  4. What You Can Do to Stop the Flu

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Flu What You Can Do to Stop the Flu Past Issues / Fall 2009 Table of Contents To ... Health and Human Services: http://flu.gov NIH Flu Research to Results Scientists at the National Institute ...

  5. Inferring Stop-Locations from WiFi.

    Directory of Open Access Journals (Sweden)

    David Kofoed Wind

    Full Text Available Human mobility patterns are inherently complex. In terms of understanding these patterns, the process of converting raw data into series of stop-locations and transitions is an important first step which greatly reduces the volume of data, thus simplifying the subsequent analyses. Previous research into the mobility of individuals has focused on inferring 'stop locations' (places of stationarity from GPS or CDR data, or on detection of state (static/active. In this paper we bridge the gap between the two approaches: we introduce methods for detecting both mobility state and stop-locations. In addition, our methods are based exclusively on WiFi data. We study two months of WiFi data collected every two minutes by a smartphone, and infer stop-locations in the form of labelled time-intervals. For this purpose, we investigate two algorithms, both of which scale to large datasets: a greedy approach to select the most important routers and one which uses a density-based clustering algorithm to detect router fingerprints. We validate our results using participants' GPS data as well as ground truth data collected during a two month period.

  6. Detector for recoil nuclei stopping in the spark chamber gas

    International Nuclear Information System (INIS)

    Aleksanyan, A.S.; Asatiani, T.L.; Ivanov, V.I.; Mkrtchyan, G.G.; Pikhtelev, R.N.

    1974-01-01

    A detector consisting of the combination of a drift and a wide gap spark chambers and designed to detect recoil nuclei stopping in the spark chamber gas is described. It is shown, that by using an appropriate discrimination the detector allows to detect reliably the recoil nuclei in the presence of intensive electron and γ-quanta beams

  7. On a rational stopping rule for facilities location algorithms

    DEFF Research Database (Denmark)

    Juel, Henrik

    1984-01-01

    In the multifacility location problem, a number of new facilities are to be located so as to minimize a sum of weighted distances. Love and Yeong (1981) developed a lower bound on the optimal value for use in deciding when to stop an iterative solution procedure. The authors develop a stronger...

  8. Stopping particles in the Mont Blanc spark chamber telescopes

    Energy Technology Data Exchange (ETDEWEB)

    Bergamasco, L; Bilokon, H; Piazzoli, B E; Mannocchi, G; Picchi, P [Consiglio Nazionale delle Ricerche, Turin (Italy). Lab. di Cosmo-Geofisica; Turin Univ. (Italy). Ist. di Fisica Generale)

    1982-02-01

    We present the final results on the ratio of stopping to traversing muons as measured by two spark chamber telescopes in the Mont Blanc Station, Italy, at 4300 hg/cm/sup 2/. The experimental results are in agreement with the theoretical values within the limits of the error.

  9. 32 CFR 636.30 - Stopping, standing and parking.

    Science.gov (United States)

    2010-07-01

    ... ENFORCEMENT AND CRIMINAL INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION (SPECIFIC INSTALLATIONS) Fort... which obstructs traffic. (g) No driver will stand or park a vehicle, whether occupied or not, except...) Within 20 feet upon the approach to any flashing signal, a stop sign, yield sign, or traffic control...

  10. Inferring Stop-Locations from WiFi

    DEFF Research Database (Denmark)

    Wind, David Kofoed; Sapiezynski, Piotr; Furman, Magdalena Anna

    2016-01-01

    methods are based exclusively on WiFi data. We study two months of WiFi data collected every two minutes by a smartphone, and infer stop-locations in the form of labelled time-intervals. For this purpose, we investigate two algorithms, both of which scale to large datasets: a greedy approach to select...

  11. 14 CFR 25.109 - Accelerate-stop distance.

    Science.gov (United States)

    2010-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Flight Performance § 25.109 Accelerate-stop distance. (a...) The maximum tire-to-ground wet runway braking coefficient of friction is defined as: ER18FE98.004 Where— Tire Pressure=maximum airplane operating tire pressure (psi); μt/gMAX=maximum tire-to-ground...

  12. Annihilation of antiprotons stopped in liquid hydrogen and deuterium

    International Nuclear Information System (INIS)

    Dalkarov, O.D.; Kerbikov, B.O.; Markushin, V.E.

    1976-01-01

    Detailed analysis is given of stopping antiproton annihilation in liquid hydrogen and deuterium. Connection between capture schedule and properties of bound states in nucleon-antinucleon system is established. The theoretical predictions are compared with experimental data which appeared in 1971-75

  13. Theoretical model for calculation of molecular stopping power

    International Nuclear Information System (INIS)

    Xu, Y.J.

    1984-01-01

    A modified local plasma model based on the work of Linhard-Winther, Bethe, Brown, and Walske is established. The Gordon-Kim's molecular charged density model is employed to obtain a formula to evaluate the stopping power of many useful molecular systems. The stopping power of H 2 and He gas was calculated for incident proton energy ranging from 100 KeV to 2.5 MeV. The stopping power of O 2 , N 2 , and water vapor was also calculated for incident proton energy ranging from 40 keV to 2.5 MeV. Good agreement with experimental data was obtained. A discussion of molecular effects leading to departure from Bragg's rule is presented. The equipartition rule and the effect of nuclear momentum recoiling in stopping power are also discussed in the appendix. The calculation procedure presented hopefully can easily be extended to include the most useful organic systems such as the molecules composed of carbon, nitrogen, hydrogen and oxygen which are useful in radiation protection field

  14. Assessing One-stop-shop Best Practices for South African ...

    African Journals Online (AJOL)

    One stop shop (OSS) models are an investment process that came about to create a centralised place for the voluminous documentation required in international trade between companies. Bureaucracy has proven to be a major barrier to the development of international trade, particularly in African countries that still lag ...

  15. Reasons for Starting and Stopping Electronic Cigarette Use

    Directory of Open Access Journals (Sweden)

    Jessica K. Pepper

    2014-10-01

    Full Text Available The aim of our study was to explore reasons for starting and then stopping electronic cigarette (e-cigarette use. Among a national sample of 3878 U.S. adults who reported ever trying e-cigarettes, the most common reasons for trying were curiosity (53%; because a friend or family member used, gave, or offered e-cigarettes (34%; and quitting or reducing smoking (30%. Nearly two-thirds (65% of people who started using e-cigarettes later stopped using them. Discontinuation was more common among those whose main reason for trying was not goal-oriented (e.g., curiosity than goal-oriented (e.g., quitting smoking (81% vs. 45%, p < 0.001. The most common reasons for stopping e-cigarette use were that respondents were just experimenting (49%, using e-cigarettes did not feel like smoking cigarettes (15%, and users did not like the taste (14%. Our results suggest there are two categories of e-cigarette users: those who try for goal-oriented reasons and typically continue using and those who try for non-goal-oriented reasons and then typically stop using. Research should distinguish e-cigarette experimenters from motivated users whose decisions to discontinue relate to the utility or experience of use. Depending on whether e-cigarettes prove to be effective smoking cessation tools or whether they deter cessation, public health programs may need distinct strategies to reach and influence different types of users.

  16. Reasons for starting and stopping electronic cigarette use.

    Science.gov (United States)

    Pepper, Jessica K; Ribisl, Kurt M; Emery, Sherry L; Brewer, Noel T

    2014-10-03

    The aim of our study was to explore reasons for starting and then stopping electronic cigarette (e-cigarette) use. Among a national sample of 3878 U.S. adults who reported ever trying e-cigarettes, the most common reasons for trying were curiosity (53%); because a friend or family member used, gave, or offered e-cigarettes (34%); and quitting or reducing smoking (30%). Nearly two-thirds (65%) of people who started using e-cigarettes later stopped using them. Discontinuation was more common among those whose main reason for trying was not goal-oriented (e.g., curiosity) than goal-oriented (e.g., quitting smoking) (81% vs. 45%, p reasons for stopping e-cigarette use were that respondents were just experimenting (49%), using e-cigarettes did not feel like smoking cigarettes (15%), and users did not like the taste (14%). Our results suggest there are two categories of e-cigarette users: those who try for goal-oriented reasons and typically continue using and those who try for non-goal-oriented reasons and then typically stop using. Research should distinguish e-cigarette experimenters from motivated users whose decisions to discontinue relate to the utility or experience of use. Depending on whether e-cigarettes prove to be effective smoking cessation tools or whether they deter cessation, public health programs may need distinct strategies to reach and influence different types of users.

  17. Drinking and driving behavior at stop signs and red lights.

    Science.gov (United States)

    Wan, Jingyan; Wu, Changxu; Zhang, Yiqi; Houston, Rebecca J; Chen, Chang Wen; Chanawangsa, Panya

    2017-07-01

    Alcohol is one of the principal risk factors for motor vehicle crashes. One factor that contributes to vehicle crashes is noncompliance with stop signs and red lights. The present experiment investigated the effects of alcohol and drinking patterns on driving behavior at stop signs and red lights. 28 participants participated in drinking and simulated driving sessions during which they received a moderate dose of alcohol (0.08% BAC) or a placebo. Simulated driving tasks measured participants' driving performance at stop signs and red lights in response to each dose. Results suggested that alcohol impaired the driver control of speed and direction and prolonged their simple and complex reaction time, which were exhibited by impaired speed and lateral control, longer reaction time when the lights turned yellow, and lower deceleration towards stop signs and red lights. Visual degradation may also occur under alcohol intake. It was also suggested that alcohol impaired non-binge drinkers more severely. To be specific, higher acceleration was observed in impaired non-binge drinkers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. "STOP the Violence": FCCLA Program Tackles School Issue

    Science.gov (United States)

    Journal of Family and Consumer Sciences, 2004

    2004-01-01

    "STOP the Violence--Students Taking on Prevention" is a program designed to involve students and address school violence at its core from the peer-to- peer perspective. Developed by members of the Family, Career and Community Leaders of America (FCCLA), the program empowers young persons to recognize, report, and reduce the potential for youth…

  19. A Connection between Singular Stochastic Control and Optimal Stopping

    International Nuclear Information System (INIS)

    Espen Benth, Fred; Reikvam, Kristin

    2003-01-01

    We show that the value function of a singular stochastic control problem is equal to the integral of the value function of an associated optimal stopping problem. The connection is proved for a general class of diffusions using the method of viscosity solutions

  20. Stopping Power of Solid Argon for Helium Ions

    DEFF Research Database (Denmark)

    Besenbacher, F.; Bøttiger, Jørgen; Grauersen, O.

    1981-01-01

    By means of the Rutherford-backscattering method, the stopping cross section of solid argon has been measured for 0.5–3 MeV helium ions to an accuracy of not, vert, similar3%. The results agree within the experimental accuracies with our earlier measurements for gaseous argon over the energy region...