Science.gov

Sample records for 3rd codon positions

  1. The most deviated codon position in AT-rich bacterial genomes: a function related analysis.

    PubMed

    Ma, Bin-Guang; Chen, Ling-Ling

    2005-10-01

    We have performed systematic study on more than 120 archaeal and bacterial genomes. Based on the index proposed in the current paper, clear patterns are observed showing the relation between the base compositional deviation at three codon positions and the genomic GC content. For AT-rich genomes, the Most Deviated Codon Position (MDCP) is the 1st codon position, while for GC-rich genomes, MDCP appears at the 2nd or 3rd codon position alternatively. According to MDCP, the CDSs of a genome can be classified into two types: typical and atypical. In AT-rich genomes the typical represent the majority and account for about 3/4 of all the CDSs. Based on the functional classification of COG database, the two types of CDSs are examined. An apparent bias of distribution is observed that the CDSs with the function of 'information processing' are more likely to present in typical type. PMID:16060688

  2. Model for Codon Position Bias in RNA Editing

    NASA Astrophysics Data System (ADS)

    Liu, Tsunglin; Bundschuh, Ralf

    2005-08-01

    RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of Physarum polycephalum, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in Physarum. This suggests that the codon position bias in Physarum is mainly a consequence of selection at the protein level.

  3. A model for codon position bias in RNA editing

    NASA Astrophysics Data System (ADS)

    Bundschuh, Ralf; Liu, Tsunglin

    2006-03-01

    RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of Physarum polycephalum, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in Physarum. This suggests that the codon position bias in Physarum is mainly a consequence of selection at the protein level.

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

    NASA Astrophysics Data System (ADS)

    Mitarai, Namiko; Pedersen, Steen

    2013-10-01

    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.

  5. Recurrent positive selection and heterogeneous codon usage bias events leading to coexistence of divergent pigeon circoviruses.

    PubMed

    Liao, Pei-Chun; Wang, Kung-Kai; Tsai, Shinn-Shyong; Liu, Hung-Jen; Huang, Bing-Hong; Chuang, Kuo-Pin

    2015-08-01

    The capsid genes from 14 pigeon circovirus (PiCV) sequences, collected from Taiwan between 2009 and 2010, were sequenced and compared with 14 PiCV capsid gene sequences from GenBank. Based on pairwise comparison, PiCV strains from Taiwan shared 73.9-100% nucleotide identity and 72-100% amino acid identity with those of the 14 reported PiCV sequences. Phylogenetic analyses revealed that Taiwanese PiCV isolates can be grouped into two clades: clade 1 comprising isolates from Belgium, Australia, USA, Italy and China, and clade 2 showing close relation to isolates from Germany and France. Recurrent positive selection was detected in clade 1 PiCV lineages, which may contribute to the diversification of predominant PiCV sequences in Taiwan. Further observations suggest that synonymous codon usage variations between PiCV clade 1 and clade 2 may reflect the adaptive divergence on translation efficiency of capsid genes in infectious hosts. Variation in selective pressures acting on the evolutionary divergence and codon usage bias of both clades explains the regional coexistence of virus sequences congeners prevented from competitive exclusion within an island such as Taiwan. Our genotyping results also provide insight into the aetiological agents of PiCV outbreak in Taiwan and we present a comparative analysis of the central coding region of PiCV genome. From the sequence comparison results of 28 PiCVs which differs in regard to the geographical origin and columbid species, we identified conserved regions within the capsid gene that are likely to be suitable for primer selection and vaccine development. PMID:25911731

  6. Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning.

    PubMed

    Berry, Katherine E; Waghray, Shruti; Mortimer, Stefanie A; Bai, Yun; Doudna, Jennifer A

    2011-10-12

    Translation of hepatitis C viral proteins requires an internal ribosome entry site (IRES) located in the 5' untranslated region of the viral mRNA. The core domain of the hepatitis C virus (HCV) IRES contains a four-way helical junction that is integrated within a predicted pseudoknot. This domain is required for positioning the mRNA start codon correctly on the 40S ribosomal subunit during translation initiation. Here, we present the crystal structure of this RNA, revealing a complex double-pseudoknot fold that establishes the alignment of two helical elements on either side of the four-helix junction. The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit. This structure, representing the last major domain of HCV-like IRESs to be determined at near-atomic resolution, provides the basis for a comprehensive cryoelectron microscopy-guided model of the intact HCV IRES and its interaction with 40S ribosomal subunits. PMID:22000514

  7. Focusing the Debate for Positive Change in Teacher Education. Proceedings of the Forum on Teacher Education (3rd, Little Rock, Arkansas, March 1987).

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    In the third regional forum on positive change in teacher education, two themes dominated discussions: the pros and cons of the "fifth-year" plan for teacher education, and the impact and future of standardized testing. In both areas, a major emphasis on traditonally black institutions emerged. This report outlines the discussions, and presents…

  8. Codon usage patterns in Chinese bayberry (Myrica rubra) based on RNA-Seq data

    PubMed Central

    2013-01-01

    Background Codon usage analysis has been a classical topic for decades and has significances for studies of evolution, mRNA translation, and new gene discovery, etc. While the codon usage varies among different members of the plant kingdom, indicating the necessity for species-specific study, this work has mostly been limited to model organisms. Recently, the development of deep sequencing, especial RNA-Seq, has made it possible to carry out studies in non-model species. Result RNA-Seq data of Chinese bayberry was analyzed to investigate the bias of codon usage and codon pairs. High frequency codons (AGG, GCU, AAG and GAU), as well as low frequency ones (NCG and NUA codons) were identified, and 397 high frequency codon pairs were observed. Meanwhile, 26 preferred and 141 avoided neighboring codon pairs were also identified, which showed more significant bias than the same pairs with one or more intervening codons. Codon patterns were also analyzed at the plant kingdom, organism and gene levels. Changes during plant evolution were evident using RSCU (relative synonymous codon usage), which was even more significant than GC3s (GC content of 3rd synonymous codons). Nine GO categories were differentially and independently influenced by CAI (codon adaptation index) or GC3s, especially in 'Molecular function’ category. Within a gene, the average CAI increased from 0.720 to 0.785 in the first 50 codons, and then more slowly thereafter. Furthermore, the preferred as well as avoided codons at the position just following the start codon AUG were identified and discussed in relation to the key positions in Kozak sequences. Conclusion A comprehensive codon usage Table and number of high-frequency codon pairs were established. Bias in codon usage as well as in neighboring codon pairs was observed, and the significance of this in avoiding DNA mutation, increasing protein production and regulating protein synthesis rate was proposed. Codon usage patterns at three levels were

  9. The ribosome prohibits the G•U wobble geometry at the first position of the codon-anticodon helix.

    PubMed

    Rozov, Alexey; Westhof, Eric; Yusupov, Marat; Yusupova, Gulnara

    2016-07-27

    Precise conversion of genetic information into proteins is essential to cellular health. However, a margin of error exists and is at its highest on the stage of translation of mRNA by the ribosome. Here we present three crystal structures of 70S ribosome complexes with messenger RNA and transfer RNAs and show that when a G•U base pair is at the first position of the codon-anticodon helix a conventional wobble pair cannot form because of inescapable steric clash between the guanosine of the A codon and the key nucleotide of decoding center adenosine 1493 of 16S rRNA. In our structure the rigid ribosomal decoding center, which is identically shaped for cognate or near-cognate tRNAs, forces this pair to adopt a geometry close to that of a canonical G•C pair. We further strengthen our hypothesis that spatial mimicry due either to base tautomerism or ionization dominates the translation infidelity mechanism. PMID:27174928

  10. Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

    PubMed Central

    2010-01-01

    Background CC chemokine receptor proteins (CCR1 through CCR10) are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions. In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events. Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML) were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR) gene family. The results of neutral vs. adaptive evolution (positive selection) hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω) >1. Results Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive selection code for amino acid

  11. 2nd & 3rd Generation Vehicle Subsystems

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This paper contains viewgraph presentation on the "2nd & 3rd Generation Vehicle Subsystems" project. The objective behind this project is to design, develop and test advanced avionics, power systems, power control and distribution components and subsystems for insertion into a highly reliable and low-cost system for a Reusable Launch Vehicles (RLV). The project is divided into two sections: 3rd Generation Vehicle Subsystems and 2nd Generation Vehicle Subsystems. The following topics are discussed under the first section, 3rd Generation Vehicle Subsystems: supporting the NASA RLV program; high-performance guidance & control adaptation for future RLVs; Evolvable Hardware (EHW) for 3rd generation avionics description; Scaleable, Fault-tolerant Intelligent Network or X(trans)ducers (SFINIX); advance electric actuation devices and subsystem technology; hybrid power sources and regeneration technology for electric actuators; and intelligent internal thermal control. Topics discussed in the 2nd Generation Vehicle Subsystems program include: design, development and test of a robust, low-maintenance avionics with no active cooling requirements and autonomous rendezvous and docking systems; design and development of a low maintenance, high reliability, intelligent power systems (fuel cells and battery); and design of a low cost, low maintenance high horsepower actuation systems (actuators).

  12. BACODINE/3rd Interplanetary Network burst localization

    SciTech Connect

    Hurley, K.; Barthelmy, S.; Butterworth, P.; Cline, T.; Sommer, M.; Boer, M.; Niel, M.; Kouveliotou, C.; Fishman, G.; Meegan, C.

    1996-08-01

    Even with only two widely separated spacecraft (Ulysses and GRO), 3rd Interplanetary Network (IPN) localizations can reduce the areas of BATSE error circles by two orders of magnitude. Therefore it is useful to disseminate them as quickly as possible following BATSE bursts. We have implemented a system which transmits the light curves of BACODINE/BATSE bursts directly by e-mail to UC Berkeley immediately after detection. An automatic e-mail parser at Berkeley watches for these notices, determines the Ulysses crossing time window, and initiates a search for the burst data on the JPL computer as they are received. In ideal cases, it is possible to retrieve the Ulysses data within a few hours of a burst, generate an annulus of arrival directions, and e-mail it out to the astronomical community by local nightfall. Human operators remain in this loop, but we are developing a fully automated routine which should remove them, at least for intense events, and reduce turn-around times to an absolute minimum. We explain the current operations, the data types used, and the speed/accuracy tradeoffs.

  13. Positions of Trp codons in the leader peptide-coding region of the at operon influence anti-trap synthesis and trp operon expression in Bacillus licheniformis.

    PubMed

    Levitin, Anastasia; Yanofsky, Charles

    2010-03-01

    Tryptophan, phenylalanine, tyrosine, and several other metabolites are all synthesized from a common precursor, chorismic acid. Since tryptophan is a product of an energetically expensive biosynthetic pathway, bacteria have developed sensing mechanisms to downregulate synthesis of the enzymes of tryptophan formation when synthesis of the amino acid is not needed. In Bacillus subtilis and some other Gram-positive bacteria, trp operon expression is regulated by two proteins, TRAP (the tryptophan-activated RNA binding protein) and AT (the anti-TRAP protein). TRAP is activated by bound tryptophan, and AT synthesis is increased upon accumulation of uncharged tRNA(Trp). Tryptophan-activated TRAP binds to trp operon leader RNA, generating a terminator structure that promotes transcription termination. AT binds to tryptophan-activated TRAP, inhibiting its RNA binding ability. In B. subtilis, AT synthesis is upregulated both transcriptionally and translationally in response to the accumulation of uncharged tRNA(Trp). In this paper, we focus on explaining the differences in organization and regulatory functions of the at operon's leader peptide-coding region, rtpLP, of B. subtilis and Bacillus licheniformis. Our objective was to correlate the greater growth sensitivity of B. licheniformis to tryptophan starvation with the spacing of the three Trp codons in its at operon leader peptide-coding region. Our findings suggest that the Trp codon location in rtpLP of B. licheniformis is designed to allow a mild charged-tRNA(Trp) deficiency to expose the Shine-Dalgarno sequence and start codon for the AT protein, leading to increased AT synthesis. PMID:20061467

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

    PubMed

    Hauber, David J; Grogan, Dennis W; DeBry, Ronald W

    2016-01-01

    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. PMID:26727272

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

    PubMed Central

    Hauber, David J.; Grogan, Dennis W.; DeBry, Ronald W.

    2016-01-01

    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. PMID:26727272

  16. AT2-AT3-profiling: a new look at synonymous codon usage.

    PubMed

    Pluhar, Wolfgang

    2006-12-01

    The teleology of synonymous codon usage (SCU) still awaits a unifying concept. Here the 2nd codon letter of human mRNA-codons was graphically, aided by a computer program, put in relation to the 3rd codon letter, the carrier of SCU: AT2, the density of A+T in 2nd codon position, behaves to AT3, the analogous density of the 3rd codon position, mostly in an inverse fashion that can be expressed as typical figures: mRNAs with an overall AT-density below 50% have a tendency to produce bulky figures called "red dragons" (when redness is attributed to graph-areas, where AT3< AT2), while mRNAs with an AT-density above 50% produce a pattern called "harlequin" consisting of alternating red and blue (blueness, in analogy, when AT3>AT2) diamonds. With more diversion of AT3 from AT2, the harlequin patterns can assume the pattern of a "blue dragon". By analysing the mRNA of known proteins, these patterns can be correlated with certain functional regions: proteins with multiple transmembrane passages show bulky "red dragons", structural proteins with a high glycine- and proline content such as collagen result in "blue dragons". Non-coding mRNAs tend to show a balance between AT2 and AT3 and hence "harlequin patterns". Signal peptides usually code red due to a low AT3 with an AT2-density at the expectance level. With this technique DNA-sequences of as yet unknown functional meaning were scanned. When stretches of harlequin patterns appear interrupted by red or blue dragons, closer scrutiny of these stretches can reveal ORFs which deserve to be looked at more closely for their protein-informational content. At least in humans, SCU appears to follow protein-dependent AT2-density in a reciprocal fashion and does not seem to serve the purpose of influencing mRNA secondary structure which is discussed in depth. PMID:16930630

  17. Presenting the 3rd edition of WRB

    NASA Astrophysics Data System (ADS)

    Schad, Peter

    2014-05-01

    The third edition of the international soil classification system "World Reference Base for Soil Resources" (WRB) will be presented during der 20th World Congress of Soil Science, Jeju, Korea, June 9-12. The second edition was published in 2006 and the first in 1998, which, in turn, was based on the Legends of the FAO Soil Map of the World. Now, after eight years of experience with the second edition, time was due for a revision. The major changes are: 1. The second edition had two different qualifier sequences for naming soils (IUSS Working Group WRB, 2006, update 2007) and for creating map legends (Guidelines for creating small-scale map legends using the WRB; IUSS Working Group WRB, 2010). The third edition has one sequence for both. The qualifiers for every Reference Soil Group are subdivided into a small number of main qualifiers that are ranked and a larger number of additional qualifiers that are not ranked and given in an alphabetical order. The name of a pedon must comprise all applying qualifiers. The name of a map unit comprises a specified small number of main qualifiers, depending on scale, whereas all other qualifiers are optional. 2. For some soils, problems have been reported. Albeluvisols are difficult to detect in the field and cover only small surfaces. They have been replaced by Retisols, which have a broader definition that is easier to identify in the field. 3. The use of some diagnostics was difficult. Examples are: The argic horizon had too low limit values, so we had much more soils with argic horizons than justified. The definitions of the cambic horizon and the gleyic and stagnic properties were not precise enough. Organic material, mollic and umbric horizons had an unnecessary complicated definition. 4. Some changes in the key to the Reference Soil Groups seemed to be justified. Fluvisols were moved further down, Durisols and Gypsisols switched their position, also Arenosols and Cambisols. The soils with an argic horizon were brought

  18. PREFACE: 3rd International Congress on Mechanical Metrology (CIMMEC2014)

    NASA Astrophysics Data System (ADS)

    2015-10-01

    From October 14th to 16th 2014, The Brazilian National Institute of Metrology, Quality, and Technology (Inmetro) and the Brazilian Society of Metrology (SBM) organized the 3rd International Congress on Mechanical Metrology (3rd CIMMEC). The 3rd CIMMEC was held in the city of Gramado, Rio Grande do Sul, Brazil. Anticipating the interest and enthusiasm of the technical-scientific community, the Organizing Institutions invite people and organizations to participate in this important congress, reiterating the commitment to organize an event according to highest international standards. This event has been conceived to integrate people and organizations from Brazil and abroad in the discussion of advanced themes in metrology. Manufacturers and dealers of measuring equipment and standards, as well as of auxiliary accessories and bibliographic material, had the chance to promote their products and services in stands at the Fair, which has taken place alongside the Congress. The 3rd CIMMEC consisted of five Keynote Speeches and 116 regular papers. Among the regular papers, the 25 most outstanding ones, comprising a high quality content on Mechanical Metrology, were selected to be published in this issue of Journal of Physics: Conference Series. It is our great pleasure to present this volume of Journal of Physics: Conference Series to the scientific community to promote further research in Mechanical Metrology and related areas. We believe that this volume will be both an excellent source of scientific material in the fast evolving fields that were covered by CIMMEC 2014.

  19. National--Alliance for Arts Education; JDR 3rd Fund

    ERIC Educational Resources Information Center

    Rogers, Forbes W.; Bloom, Kathryn

    1978-01-01

    The Alliance for Arts Education is an educational project embracing organizations and individuals at the national, state, and local levels with a mutual commitment to the arts as an integral part of the educational process. The JDR 3rd Fund provides consultant and technical services and, through coordination of the League of Cities for the Arts in…

  20. Codon usage trend in mitochondrial CYB gene.

    PubMed

    Uddin, Arif; Chakraborty, Supriyo

    2016-07-15

    Here we reported the pattern of codon usage and the factors which influenced the codon usage pattern in mitochondrial cytochrome B (MT-CYB) gene among pisces, aves and mammals. The F1 axis of correspondence analysis showed highly significant positive correlation with nucleobases A3, C and C3 and significant negative correlation with T and T3 while F2 of correspondence analysis showed significant positive correlation with C and C3 and significant negative correlation with A and A3. From the neutrality plot, it was evident that the GC12 was influenced by mutation pressure and natural selection with a ratio of 0.10/0.90=0.11 in pisces, 0.024/0.976=0.0245 in aves and in mammals 0.215/0.785=0.273, which indicated that the role of natural selection was more than mutation pressure on structuring the bases at the first and second codon positions. Natural selection played the major role; but compositional constraint and mutation pressure also played a significant role in codon usage pattern. Analysis of codon usage pattern has contributed to the better understanding of the mechanism of distribution of codons and the evolution of MT-CYB gene. PMID:27063508

  1. 75 FR 55313 - Record of Decision (ROD) for Conversion of the 3rd Armored Cavalry Regiment (3rd ACR) to a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... Department of the Army Record of Decision (ROD) for Conversion of the 3rd Armored Cavalry Regiment (3rd ACR...: Notice of Availability (NOA). SUMMARY: The Department of the Army announces a ROD for conversion of the... conversion, the 3rd ACR will provide the Army with a force structure that has the flexibility to...

  2. 3rd latin american and Caribbean congress on health economics.

    PubMed

    Pérez Izquierdo, Victoria; Alvarez Muñiz, Manuel

    2009-02-01

    The 3rd Latin American and Caribbean Congress on Health Economics took place at Havana Convention Center from 28th to 31st October 2008. The conference was an excellent opportunity for the exchange of personal encounters regarding health economics and its related disciplines from the perspectives of research, teaching and management. Specialists from mostly Latin American countries attended the event. High-ranking specialists from other countries highlighted the importance and popularity of the conference. A total of 313 delegates from 23 countries were present at the congress, 160 of whom were Cuban. PMID:19371176

  3. Precipitation Model Validation in 3rd Generation Aeroturbine Disc Alloys

    NASA Technical Reports Server (NTRS)

    Olson, G. B.; Jou, H.-J.; Jung, J.; Sebastian, J. T.; Misra, A.; Locci, I.; Hull, D.

    2008-01-01

    In support of application of the DARPA-AIM methodology to the accelerated hybrid thermal process optimization of 3rd generation aeroturbine disc alloys with quantified uncertainty, equilibrium and diffusion couple experiments have identified available fundamental thermodynamic and mobility databases of sufficient accuracy. Using coherent interfacial energies quantified by Single-Sensor DTA nucleation undercooling measurements, PrecipiCalc(TM) simulations of nonisothermal precipitation in both supersolvus and subsolvus treated samples show good agreement with measured gamma particle sizes and compositions. Observed longterm isothermal coarsening behavior defines requirements for further refinement of elastic misfit energy and treatment of the parallel evolution of incoherent precipitation at grain boundaries.

  4. Designing a 3rd generation, authenticatable attribute measurement system

    SciTech Connect

    Thron, Jonathan; Karpius, Peter; Santi, Peter; Smith, Morag; Vo, Duc; Williams, Richard

    2009-01-01

    Attribute measurement systems (AMS) are designed to measure potentially sensitive items containing Special Nuclear Materials to determine if the items possess attributes which fall within an agreed-upon range. Such systems could be used in a treaty to inspect and verify the identity of items in storage without revealing any sensitive information associated with the item. An AMS needs to satisfy two constraints: the host party needs to be sure that none of their sensitive information is released, while the inspecting party wants to have confidence that the limited amount of information they see accurately reflects the properties of the item being measured. The former involves 'certifying' the system and the latter 'authenticating' it. Previous work into designing and building AMS systems have focused more on the questions of certifiability than on the questions of authentication - although a few approaches have been investigated. The next step is to build a 3rd generation AMS which (1) makes the appropriate measurements, (2) can be certified, and (3) can be authenticated (the three generations). This paper will discuss the ideas, options, and process of producing a design for a 3rd generation AMS.

  5. Microstructure Modeling of 3rd Generation Disk Alloys

    NASA Technical Reports Server (NTRS)

    Jou, Herng-Jeng

    2010-01-01

    The objective of this program is to model, validate, and predict the precipitation microstructure evolution, using PrecipiCalc (QuesTek Innovations LLC) software, for 3rd generation Ni-based gas turbine disc superalloys during processing and service, with a set of logical and consistent experiments and characterizations. Furthermore, within this program, the originally research-oriented microstructure simulation tool will be further improved and implemented to be a useful and user-friendly engineering tool. In this report, the key accomplishment achieved during the second year (2008) of the program is summarized. The activities of this year include final selection of multicomponent thermodynamics and mobility databases, precipitate surface energy determination from nucleation experiment, multiscale comparison of predicted versus measured intragrain precipitation microstructure in quench samples showing good agreement, isothermal coarsening experiment and interaction of grain boundary and intergrain precipitates, primary microstructure of subsolvus treatment, and finally the software implementation plan for the third year of the project. In the following year, the calibrated models and simulation tools will be validated against an independently developed experimental data set, with actual disc heat treatment process conditions. Furthermore, software integration and implementation will be developed to provide material engineers valuable information in order to optimize the processing of the 3rd generation gas turbine disc alloys.

  6. 3rd grade English language learners making sense of sound

    NASA Astrophysics Data System (ADS)

    Suarez, Enrique; Otero, Valerie

    2013-01-01

    Despite the extensive body of research that supports scientific inquiry and argumentation as cornerstones of physics learning, these strategies continue to be virtually absent in most classrooms, especially those that involve students who are learning English as a second language. This study presents results from an investigation of 3rd grade students' discourse about how length and tension affect the sound produced by a string. These students came from a variety of language backgrounds, and all were learning English as a second language. Our results demonstrate varying levels, and uses, of experiential, imaginative, and mechanistic reasoning strategies. Using specific examples from students' discourse, we will demonstrate some of the productive aspects of working within multiple language frameworks for making sense of physics. Conjectures will be made about how to utilize physics as a context for English Language Learners to further conceptual understanding, while developing their competence in the English language.

  7. Results from the UK 3rd generation programme: Albion

    NASA Astrophysics Data System (ADS)

    McEwen, R. K.; Axcell, C.; Knowles, P.; Hoade, K. P.; Wilson, M.; Dennis, P. N. J.; Backhouse, P.; Gordon, N. T.

    2008-10-01

    Following the development of 1st Generation systems in the 1970s, thermal imaging has been in service with the UK armed forces for over 25 years and has proven itself to be a battle winning technology. More recently the wider accessibility to similar technologies within opposing forces has reduced the military advantage provided by these 1st Generation systems and a clear requirement has been identified by the UK MOD for thermal imaging sensors providing increased detection, recognition and identification (DRI) ranges together with a simplified logistical deployment burden and reduced through-life costs. In late 2005, the UK MOD initiated a programme known as "Albion" to develop high performance 3rd Generation single waveband infrared detectors to meet this requirement. At the same time, under a separate programme supporting higher risk technology, a dual waveband infrared detector was also developed. The development phase of the Albion programme has now been completed and prototype detectors are now available and have been integrated into demonstration thermal imaging cameras. The Albion programme has now progressed into the second phase, incorporating both single and dual waveband devices, focussing on low rate initial production (LRIP) and qualification of the devices for military applications. All of the detectors have been fabricated using cadmium mercury telluride material (CMT), grown by metal organic vapour phase epitaxy (MOVPE) on low cost, gallium arsenide (GaAs) substrates and bump bonded to the silicon read out circuit (ROIC). This paper discusses the design features of the 3rd Generation detectors developed in the UK together with the results obtained from the prototype devices both in the laboratory and when integrated into field deployable thermal imaging cameras.

  8. Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP.

    PubMed Central

    Ghetti, B; Piccardo, P; Spillantini, M G; Ichimiya, Y; Porro, M; Perini, F; Kitamoto, T; Tateishi, J; Seiler, C; Frangione, B; Bugiani, O; Giaccone, G; Prelli, F; Goedert, M; Dlouhy, S R; Tagliavini, F

    1996-01-01

    Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA). Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8570627

  9. Codon Adaptation of Plastid Genes.

    PubMed

    Suzuki, Haruo; Morton, Brian R

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  10. Codon Adaptation of Plastid Genes

    PubMed Central

    Suzuki, Haruo; Morton, Brian R.

    2016-01-01

    Codon adaptation is codon usage bias that results from selective pressure to increase the translation efficiency of a gene. Codon adaptation has been studied across a wide range of genomes and some early analyses of plastids have shown evidence for codon adaptation in a limited set of highly expressed plastid genes. Here we study codon usage bias across all fully sequenced plastid genomes which includes representatives of the Rhodophyta, Alveolata, Cryptophyta, Euglenozoa, Glaucocystophyceae, Rhizaria, Stramenopiles and numerous lineages within the Viridiplantae, including Chlorophyta and Embryophyta. We show evidence that codon adaptation occurs in all genomes except for two, Theileria parva and Heicosporidium sp., both of which have highly reduced gene contents and no photosynthesis genes. We also show evidence that selection for codon adaptation increases the representation of the same set of codons, which we refer to as the adaptive codons, across this wide range of taxa, which is probably due to common features descended from the initial endosymbiont. We use various measures to estimate the relative strength of selection in the different lineages and show that it appears to be fairly strong in certain Stramenopiles and Chlorophyta lineages but relatively weak in many members of the Rhodophyta, Euglenozoa and Embryophyta. Given these results we propose that codon adaptation in plastids is widespread and displays the same general features as adaptation in eubacterial genomes. PMID:27196606

  11. PREFACE: 3rd International Conference on Hadron Physics (TROIA'11)

    NASA Astrophysics Data System (ADS)

    Erkol, Güray; Küçükarslan, Ayşe; Özpineci, Altuğ

    2012-03-01

    The 3rd International Conference on Hadron Physics, TROIA'11 was held at Canakkale, Turkey on 22-25 August 2011. Ozyegin University, Middle East Technical University, Canakkale Onsekiz Mart University and HadronPhysics2 Consortium sponsored the conference. Its aim was to bring together the experts and young scientists working on experimental and theoretical hadron physics. About 60 participants from 12 countries attended the conference. The topics covered included: Chiral Perturbation Theory QCD Sum Rules Effective Field Theory Exotic Hadrons Hadron Properties from Lattice QCD Experimental Results and Future Perspectives Hadronic Distribution Amplitudes The conference presentations were organized such that the morning sessions contained invited talks and the afternoon sessions were devoted to contributed talks and poster presentations. The speakers of the invited talks were: D Melikhov, M Nielsen, M Oka, E Oset, S Scherer, T T Takahashi and R Wanke. The conference venue was a resort hotel near Canakkale. As a social program, a guided full-day excursion to the excavation site of the ancient town of Troia and Assos was organized. We believe that this conference provided a medium for young scientists and experts in the field to effectively communicate and share ideas. We would like to express our sincere thanks to all participants for their contributions and stimulating discussions. We are also grateful to the Scientific Secretary, Kadir Utku Can, and all other members of the Organizing Committee for their patience and efforts. 13 February 2012 The Editors Güray Erkol Ayşe Küçükarslan Altuğ Özpineci Conference photograph

  12. PREFACE: 3rd International Meeting on Silicene (IMS-3)

    NASA Astrophysics Data System (ADS)

    Kara, Abdelkader; Enriquez, Hanna; Lemaire, Jean Louis; Oughaddou, Hamid

    2014-03-01

    . Historical summary Every two years, the STARM (science, technologie avanc\\'ee et recherche pour la Mediterran\\'ee, http://www.starm.emcmre.org/) society is organizing an international conference entitled Euro-Mediterranean Conference on Materials and Renewable Energies (EMCMRE, http://www.emcmre.org/) in countries across the Mediterranean Sea. It is in this framework that an international meeting dedicated to silicene is organized simultaneously since 2010: 1st International Meeting of Silicene (IMS-1), Safi, Morocco, 2010 2nd International Meeting of Silicene (IMS-2), Marrakech, Morocco, 2011 3rd International Meeting of Silicene (IMS-3), Istres-Marseille, France, 2013 Conference pictures are available in the PDF

  13. PREFACE: 3rd International Symposium ''Optics and its Applications''

    NASA Astrophysics Data System (ADS)

    Calvo, M. L.; Dolganova, I. N.; Gevorgyan, N.; Guzman, A.; Papoyan, A.; Sarkisyan, H.; Yurchenko, S.

    2016-01-01

    The SPIE.FOCUS Armenia: 3rd International Symposium ''Optics and its Applications'' (OPTICS-2015) http://rau.am/optics2015/ was held in Yerevan, Armenia, in the period October 1 - 5, 2015. The symposium was organized by the International Society for Optics and Photonics (SPIE), the Armenian SPIE student chapter with collaboration of the Armenian TC of ICO, the Russian-Armenian University (RAU), the Institute for Physical Research of National Academy of Sciences of Armenia (IPR of NAS), the Greek-Armenian industrial company LT-PYRKAL, and the Yerevan State University (YSU). The Symposium was co-organized by the SPIE & OSA student chapters of BMSTU, the Armenian OSA student chapter, and the SPIE student chapters of Lund University and Wroclaw University of Technology. The symposium OPTICS-2015 was dedicated to the International Year of Light and Light-Based Technologies. OPTICS-2015 was devoted to modern topics and optical technologies such as: optical properties of nanostructures, silicon photonics, quantum optics, singular optics & its applications, laser spectroscopy, strong field optics, biomedical optics, nonlinear & ultrafast optics, photonics & fiber optics, and mathematical methods in optics. OPTICS-2015 was attended by 100 scientists and students representing 17 countries: Armenia, China, Czech Republic, France, Georgia, Germany, India, Iran, Italy, Latvia, Mexico, Poland, Russia, Saudi Arabia, Sweden, Ukraine, and USA. Such a broad international community confirmed the important mission of science to be a uniting force between different countries, religions, and nations. We hope that OPTICS-2015 inspired and motivated students and young scientists to work in optics and in science in general. The present volume of Journal of Physics: Conference Series includes proceedings of the symposium covering various aspects of modern problems in optics. We are grateful to all people who were involved in the organization process. We gratefully acknowledge support from

  14. An Evidence-Based Approach to Estimating the National and State Costs of PreK-3rd. FCD Policy Brief Advancing PK-3rd. No.10

    ERIC Educational Resources Information Center

    Picus, Lawrence O.; Odden, Allan; Goetz, Michael

    2009-01-01

    This study estimates the costs of providing a high-quality PreK-3rd education approach in all 50 states plus the District of Columbia. Relying on an Evidence-Based approach to school finance adequacy, it identifies the staffing resources needed to offer high-quality integrated PreK-3rd programs and then estimates the costs of those resources. By…

  15. PREFACE: 3rd International Congress on Ceramics (ICC3)

    NASA Astrophysics Data System (ADS)

    Niihara, Koichi; Ohji, Tatsuki; Sakka, Yoshio

    2011-10-01

    Early in 2005, the American Ceramic Society, the European Ceramic Society and the Ceramic Society of Japan announced a collaborative effort to provide leadership for the global ceramics community that would facilitate the use of ceramic and glass materials. That effort resulted in an agreement to organize a new biennial series of the International Congress on Ceramics, convened by the International Ceramic Federation (ICF). In order to share ideas and visions of the future for ceramic and glass materials, the 1st International Congress on Ceramics (ICC1) was held in Canada, 2006, under the organization of the American Ceramic Society, and the 2nd Congress (ICC2) was held in Italy, 2008, hosted by the European Ceramic Society. Organized by the Ceramic Society of Japan, the 3rd Congress (ICC3) was held in Osaka, Japan, 14-18 November 2010. Incorporating the 23rd Fall Meeting of the Ceramic Society of Japan and the 20th Iketani Conference, ICC3 was also co-organized by the Iketani Science and Technology Foundation, and was endorsed and supported by ICF, Asia-Oceania Ceramic Federation (AOCF) as well as many other organizations. Following the style of the previous two successful Congresses, the program was designed to advance ceramic and glass technologies to the next generation through discussion of the most recent advances and future perspectives, and to engage the worldwide ceramics community in a collective effort to expand the use of these materials in both conventional as well as new and exciting applications. ICC3 consisted of 22 voluntarily organized symposia in the most topical and essential themes of ceramic and glass materials, including Characterization, design and processing technologies Electro, magnetic and optical ceramics and devices Energy and environment related ceramics and systems Bio-ceramics and bio-technologies Ceramics for advanced industry and safety society Innovation in traditional ceramics It also contained the Plenary Session and the

  16. 80. GENERAL VIEW TO NORTH ON 3RD AVENUE EL AT ...

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

    80. GENERAL VIEW TO NORTH ON 3RD AVENUE EL AT GUN HILL STATION. 7TH AVENUE EL EXPRESS IS VISIBLE ABOVE THE 3RD AVENUE EL WHICH JOINED ONTO THE SAME STRUCTURE AT GUN HILL ROAD. NOTE: GUN HILL ROAD IS THE NORTH TERMINUS OF THE 3RD AVENUE ELEVATED. TRAINS DID NOT CARRY PASSENGERS BEYOND THIS POINT, ALTHOUGH THE 3RD AVENUE TRACK DID EXTEND FURTHER NORTH FOR SWITCHING PURPOSES AND INTO THE YARDS. - Interborough Rapid Transit Company, Third Avenue Elevated Line, Borough of the Bronx, New York County, NY

  17. Evaluation of the "Respect Not Risk" firearm safety lesson for 3rd-graders.

    PubMed

    Liller, Karen D; Perrin, Karen; Nearns, Jodi; Pesce, Karen; Crane, Nancy B; Gonzalez, Robin R

    2003-12-01

    The purpose of this study was to evaluate the MORE HEALTH "Respect Not Risk" Firearm Safety Lesson for 3rd-graders in Pinellas County, Florida. Six schools representative of various socioeconomic levels were selected as the test sites. Qualitative and quantitative data were collected. A total of 433 matched pretests/posttests were used to determine the effectiveness of the class in increasing student knowledge about firearm safety. The results revealed a significant increase in the mean scores on the posttest compared with the pretest. Qualitative findings showed the lesson was positively received by both students and teachers, and 65% of responding students reported discussing the lesson with family members. School nurses are encouraged to take a leading role in promoting firearm injury prevention to students. PMID:14622039

  18. Structural basis for stop codon recognition in eukaryotes

    PubMed Central

    Murray, Jason; Hegde, Ramanujan S.; Ramakrishnan, V.

    2015-01-01

    Termination of protein synthesis occurs when a translating ribosome encounters one of three universally conserved stop codons: UGA, UAA, or UAG. Release factors recognise stop codons in the ribosomal A site to mediate release of the nascent chain and recycling of the ribosome. Bacteria decode stop codons using two separate release factors with differing specificities for the second and third bases1. By contrast, eukaryotes rely on an evolutionarily unrelated omnipotent release factor (eRF1) to recognise all three stop codons2. The molecular basis of eRF1 discrimination for stop codons over sense codons is not known. Here, we present electron cryo-microscopy (cryo-EM) structures at 3.5 – 3.8 Å resolution of mammalian ribosomal complexes containing eRF1 interacting with each of the three stop codons in the A site. Binding of eRF1 flips nucleotide A1825 of 18S rRNA so that it stacks on the second and third stop codon bases. This configuration pulls the fourth position base into the A site, where it is stabilised by stacking against G626 of 18S rRNA. Thus, eRF1 exploits two rRNA nucleotides also used during tRNA selection to drive mRNA compaction. Stop codons are favoured in this compacted mRNA conformation by a hydrogen-bonding network with essential eRF1 residues that constrains the identity of the bases. These results provide a molecular framework for eukaryotic stop codon recognition and have implications for future studies on the mechanisms of canonical and premature translation termination3,4. PMID:26245381

  19. Codon Bias Patterns of E. coli’s Interacting Proteins

    PubMed Central

    Dilucca, Maddalena; Cimini, Giulio; Semmoloni, Andrea; Deiana, Antonio; Giansanti, Andrea

    2015-01-01

    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. PMID:26566157

  20. Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses

    PubMed Central

    Tong, Yigang

    2014-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment. PMID:24595095

  1. [3rd Hungarian Breast Cancer Consensus Conference - Radiotherapy Guidelines].

    PubMed

    Polgár, Csaba; Kahán, Zsuzsanna; Csejtei, András; Gábor, Gabriella; Landherr, László; Mangel, László; Mayer, Árpád; Fodor, János

    2016-09-01

    The radiotherapy expert panel revised and updated the radiotherapy (RT) guidelines accepted in 2009 at the 2nd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy of the conserved breast is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence by 60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following breast conserving surgery. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated (15×2.67 Gy) whole breast irradiation and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional (25×2 Gy) whole breast irradiation. Following mastectomy RT significantly decreases the risk of locoregional recurrence and improves overall survival of patients having 1 to 3 (pN1a) or ≥4 (pN2a, pN3a) positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be omitted and substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by breast conserving surgery whole breast irradiation is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status. PMID:27579722

  2. Measurement and correction of the 3rd order resonance in the Tevatron

    SciTech Connect

    Schmidt, F.; Alexahin, Y.; Lebedev, V.; Still, D.; Valishev, A.; /Fermilab

    2006-06-01

    At Fermilab Tevatron BPM system has been recently upgraded resulting much better accuracy of beam position measurements and improvements of data acquisition for turn-by-turn measurements. That allows one to record the beam position at each turn for 8000 turns for all BPMs (118 in each plane) with accuracy of about 10-20 {micro}m. In the last decade a harmonic analysis tool has been developed at CERN that allows relating each FFT line derived from the BPM data with a particular non-linear resonance in the machine. In fact, one can even detect the longitudinal position of the sources of these resonances. Experiments have been performed at the Tevatron in which beams have been kicked to various amplitudes to analyze the 3rd order resonance. It was possible to address this rather large resonance to some regular machine sextupoles. An alternative sextupole scheme allowed the suppression of this resonance by a good factor of 2. Lastly, the experimental data are compared with model calculations.

  3. Explanatory Supplement to the Astronomical Almanac (3rd Edition)

    NASA Astrophysics Data System (ADS)

    Urban, Sean E.; Seidelmann, P. K.

    2014-01-01

    Publications and software from the the Astronomical Applications Department of the US Naval Observatory (USNO) are used throughout the world, not only in the Department of Defense for safe navigation, but by many people including other navigators, astronomers, aerospace engineers, and geodesists. Products such as The Nautical Almanac, The Astronomical Almanac, and the Multiyear Interactive Computer Almanac (MICA) are regarded as international standards. To maintain credibility, it is imperative that the methodologies employed and the data used are well documented. "The Explanatory Supplement to the Astronomical Almanac" (hereafter, "The ES") is a major source of such documentation. It is a comprehensive reference book on positional astronomy, covering the theories and algorithms used to produce The Astronomical Almanac, an annual publication produced jointly by the Nautical Almanac Office of USNO and Her Majesty's Nautical Almanac Office (HMNAO). The first edition of The ES appeared in 1961, and the second followed in 1992. Several major changes have taken place in fundamental astronomy since the second edition was published. Advances in radio observations allowed the celestial reference frame to be tied to extragalactic radio sources, thus the International Celestial Reference System replaced the FK5 system. The success of ESA's Hipparcos satellite dramatically altered observational astrometry. Improvements in Earth orientation observations lead to new precession and nutation theories. Additionally, a new positional paradigm, no longer tied to the ecliptic and equinox, was accepted. Largely because of these changes, staff at USNO and HMNAO decided the time was right for the next edition of The ES. The third edition is now available; it is a complete revision of the 1992 book. Along with subjects covered in the previous two editions, the book also contains descriptions of the major advancements in positional astronomy over the last 20 years, some of which are

  4. A comparative analysis on the synonymous codon usage pattern in viral functional genes and their translational initiation region of ASFV.

    PubMed

    Zhou, Jian-Hua; Gao, Zong-Liang; Sun, Dong-Jie; Ding, Yao-Zhong; Zhang, Jie; Stipkovits, Laszlo; Szathmary, Susan; Pejsak, Zygmunt; Liu, Yong-Sheng

    2013-04-01

    The synonymous codon usage pattern of African swine fever virus (ASFV), the similarity degree of the synonymous codon usage between this virus and some organisms and the synonymous codon usage bias for the translation initiation region of viral functional genes in the whole genome of ASFV have been investigated by some simply statistical analyses. Although both GC12% (the GC content at the first and second codon positions) and GC3% (the GC content at the third codon position) of viral functional genes have a large fluctuation, the significant correlations between GC12 and GC3% and between GC3% and the first principal axis of principle component analysis on the relative synonymous codon usage of the viral functional genes imply that mutation pressure of ASFV plays an important role in the synonymous codon usage pattern. Turning to the synonymous codon usage of this virus, the codons with U/A end predominate in the synonymous codon family for the same amino acid and a weak codon usage bias in both leading and lagging strands suggests that strand compositional asymmetry does not take part in the formation of codon usage in ASFV. The interaction between the absolute codon usage bias and GC3% suggests that other selections take part in the formation of codon usage, except for the mutation pressure. It is noted that the similarity degree of codon usage between ASFV and soft tick is higher than that between the virus and the pig, suggesting that the soft tick plays a more important role than the pig in the codon usage pattern of ASFV. The translational initiation region of the viral functional genes generally have a strong tendency to select some synonymous codons with low GC content, suggesting that the synonymous codon usage bias caused by translation selection from the host takes part in modulating the translation initiation efficiency of ASFV functional genes. PMID:23161403

  5. 19. MILL NO. 1, 3rd FLOOR, CEILING TRACKING WITH AIR ...

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

    19. MILL NO. 1, 3rd FLOOR, CEILING TRACKING WITH AIR CLEANER (BLEW DUST/LINT DOWNWARD WHILE TRAVELING ON TRACK OVER MILL MACHINERY). - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  6. 1. WEST SIDE AND ENTRY, FROM ACROSS 3RD STREET, LOOKING ...

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

    1. WEST SIDE AND ENTRY, FROM ACROSS 3RD STREET, LOOKING EAST. - Oakland Naval Supply Center, Administration Building-Dental Annex-Dispensary, Between E & F Streets, East of Third Street, Oakland, Alameda County, CA

  7. 19. OFFSHORE VIEW OF 3RD TEE, LOOKING NORTHWEST, SHOWING SOUTHEAST ...

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

    19. OFFSHORE VIEW OF 3RD TEE, LOOKING NORTHWEST, SHOWING SOUTHEAST SIDE OF TACKLE BOX IN FOREGROUND - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  8. 15. OFFSHORE VIEW OF PIER, LOOKING EASTNORTHEAST, 3RD TEE, SHOWING ...

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

    15. OFFSHORE VIEW OF PIER, LOOKING EAST-NORTHEAST, 3RD TEE, SHOWING RESTROOMS IN FOREGROUND WITH PUMPHOUSE AND TACKLE BOX BEHIND - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  9. 3rd International Conference on Turbulent Mixing and Beyond

    NASA Astrophysics Data System (ADS)

    Abarzhi, Snezhana I.; Gauthier, Serge; Keane, Christopher J.; Niemela, Joseph J.

    2013-07-01

    , technology and mathematics; (iii) TMB participants conduct highly innovative research and their interactions strengthen the community's might. Based on the success of the first and second conferences and on the recommendations of the conference round table discussions, and in response to the inquiry of the community, the Third International Conference on Turbulent Mixing and Beyond was organized. The Third International Conference on Turbulent Mixing and Beyond, TMB-2011, was held on 21-28 August 2011 at the Abdus Salam International Centre for Theoretical Physics (ICTP), Trieste, Italy. This was a highly informative and exciting meeting, and it strengthened and reaffirmed the success of TMB-2009 and 2007. The objectives of the Third International Conference on Turbulent Mixing and Beyond were to: (i) focus the integration of theory, experiments, large-scale numerical simulations and state-of-the-art technologies on the exploration of physical mechanisms of non-equilibrium dynamics, from micro to macro-scales, in both high and low energy density regimes; (ii) foster the application of innovative approaches for tackling the fundamental aspects of turbulent mixing problems and for understanding and further extending the range of applicability of canonical considerations; (iii) encourage the development of new approaches and stimulate the application of advanced data analysis techniques for unified characterization of experimental and numerical data sets, for estimation of their quality and information capacity, and for transforming data to knowledge; (iv) further develop the 'Turbulent Mixing and Beyond' community via organizing a positive and constructive collaborative environment, maintaining the quality of information flux in the community and sharing research methodologies, tools and data among the community members. The objectives were accomplished at TMB-2011. 4. Programme of TMB-2011 TMB-2011 brought together 150 participants, ranging from students to members of

  10. Analysis of synonymous codon usage patterns in seven different citrus species.

    PubMed

    Xu, Chen; Dong, Jing; Tong, Chunfa; Gong, Xindong; Wen, Qiang; Zhuge, Qiang

    2013-01-01

    We used large samples of expressed sequence tags to characterize the patterns of codon usage bias (CUB) in seven different Citrus species and to analyze their evolutionary effect on selection and base composition. We found that A- and T-ending codons are predominant in Citrus species. Next, we identified 21 codons for 18 different amino acids that were considered preferred codons in all seven species. We then performed correspondence analysis and constructed plots for the effective number of codons (ENCs) to analyze synonymous codon usage. Multiple regression analysis showed that gene expression in each species had a constant influence on the frequency of optional codons (FOP). Base composition differences between the proportions were large. Finally, positive selection was detected during the evolutionary process of the different Citrus species. Overall, our results suggest that codon usages were the result of positive selection. Codon usage variation among Citrus genes is influenced by translational selection, mutational bias, and gene length. CUB is strongly affected by selection pressure at the translational level, and gene length plays only a minor role. One possible explanation for this is that the selection-mediated codon bias is consistently strong in Citrus, which is one of the most widely cultivated fruit trees. PMID:23761955

  11. Survey of K-3rd-Grade Teachers' Knowledge of Ear Infections and Willingness to Participate in Prevention Programs

    ERIC Educational Resources Information Center

    Danhauer, Jeffrey L.; Johnson, Carole E.; Caudle, Abby T.

    2011-01-01

    Purpose: Ear infections are prevalent in kindergarten through 3rd-grade (K-3rd) children and can affect their performance at school. Chewing gum, when administered by parents and teachers, can help prevent ear infections in children. This pilot study surveyed K-3rd-grade teachers in the Santa Barbara School Districts to assess their knowledge…

  12. Characterization of Codon usage bias in the newly identified DEV UL18 gene

    NASA Astrophysics Data System (ADS)

    Chen, Xiwen; Cheng, Anchun; Wang, Mingshu; Xiang, Jun

    2011-10-01

    In this study, Codon usage bias (CUB) of DEV UL18 gene was analyzed, the results showed that codon usage bias in the DEV UL18 gene was strong bias towards the synonymous codons with A and T at the third codon position. Phylogenetic tree based on the amino acid sequences of the DEV UL18 gene and the 27 other herpesviruses revealed that UL18 gene of the DEV CHv strain and some fowl herpesviruses such as MeHV-1, GaHV-2 and GaHV-3 were clustered within a monophyletic clade and grouped within alphaherpesvirinae. The ENC-GC3S plot indicated that codon usage bias has strong species-specificity between DEV and 27 reference herpesviruses, and suggests that factors other than gene composition, such as translational selection leading to the codon usage variation among genes in different organisms, contribute to the codon usage among the different herpesviruses. Comparison of codon preferences of DEV UL18 gene with those of E. coli , yeast and humans showed that there were 20 codons showing distinct usage differences between DEV UL18 and yeast, 22 between DEV UL18 and humans, 23 between DEV UL18 and E.coli, which indicated the codon usage bias pattern in the DEV UL18 gene was similar to that of yeast. It is infered that the yeast expression system may be more suitable for the DEV UL18 expression.

  13. A detailed comparative analysis of codon usage bias in Zika virus.

    PubMed

    Cristina, Juan; Fajardo, Alvaro; Soñora, Martín; Moratorio, Gonzalo; Musto, Héctor

    2016-09-01

    Zika virus (ZIKV) is a member of the family Flaviviridae and its genome consists of a single-stranded positive sense RNA molecule with 10,794 nucleotides. Clinical manifestations of disease caused by ZIKV infection range from asymptomatic cases to an influenza-like syndrome. There is an increasing concern about the possible relation among microcephaly and ZIKV infection. To get insight into the relation of codon usage among viruses and their hosts is extremely important to understand virus survival, fitness, evasion from host's immune system and evolution. In this study, we performed a comprehensive analysis of codon usage and composition of ZIKV. The overall codon usage among ZIKV strains is similar and slightly biased. Different codon preferences in ZIKV genes in relation to codon usage of human, Aedes aegypti and Aedes albopictus genes were found. Most of the highly frequent codons are A-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. G+C compositional constraint as well as dinucleotide composition also influence the codon usage of ZIKV. The results of these studies suggest that the emergence of ZIKV outside Africa, in the Pacific and the Americas may also be reflected in ZIKV codon usage. No significant differences were found in codon usage among strains isolated from microcephaly cases and the rest of strains from the Asian cluster enrolled in these studies. PMID:27449601

  14. Radiographic findings on 3rd molars removed in 20-year-old men.

    PubMed

    Rajasuo, Ari; Peltola, Jaakko; Ventä, Irja; Murtomaa, Heikki

    2003-10-01

    In this study we assess radiographic findings characteristic of mandibular 3rd molars that had required either routine or surgical extraction. X-ray findings relating to acute pericoronitis were also examined. The material was collected by investigating patient records and rotational panoramic radiographs of 20-year-old Finnish male conscripts (n = 738) treated during military service because of 3rd-molar-related problems. The follicle around the crown of mandibular 3rd molars with acute pericoronitis was enlarged in 19% of cases and in 13% of chronic symptom-free pericoronitis cases (not statistically significant difference). Mandibular 3rd molars extracted surgically were more often mesially inclined than those extracted routinely (61% vs. 23%; P < 0.001), partially or totally intrabony impacted (92% vs. 66%; P < 0.001) and deep situated (on average 4.2 mm vs. 2.5 mm under the occlusal plane). Surgical extraction was also associated with the roots completely developed [92% vs. 84% of the teeth routinely extracted, odds ratio (OR) 2.6, 95% confidence interval (CI) 1.2-5.5] and with the absence of radiographic pericoronitis [around 27% vs. 39% of the teeth routinely extracted (OR 0.5, 95% CI 0.3-0.8)]. In 86% of cases the space between 2nd molar and ramus of the mandible was narrower than the 3rd molar extracted surgically, whereas this was 62% in routine extraction cases (P < 0.001). We conclude that there are some typical 3rd-molar findings in rotational panoramic radiographs that show a need for surgical extraction. PMID:14763776

  15. Vertebrate codon bias indicates a highly GC-rich ancestral genome.

    PubMed

    Nabiyouni, Maryam; Prakash, Ashwin; Fedorov, Alexei

    2013-04-25

    Two factors are thought to have contributed to the origin of codon usage bias in eukaryotes: 1) genome-wide mutational forces that shape overall GC-content and create context-dependent nucleotide bias, and 2) positive selection for codons that maximize efficient and accurate translation. Particularly in vertebrates, these two explanations contradict each other and cloud the origin of codon bias in the taxon. On the one hand, mutational forces fail to explain GC-richness (~60%) of third codon positions, given the GC-poor overall genomic composition among vertebrates (~40%). On the other hand, positive selection cannot easily explain strict regularities in codon preferences. Large-scale bioinformatic assessment, of nucleotide composition of coding and non-coding sequences in vertebrates and other taxa, suggests a simple possible resolution for this contradiction. Specifically, we propose that the last common vertebrate ancestor had a GC-rich genome (~65% GC). The data suggest that whole-genome mutational bias is the major driving force for generating codon bias. As the bias becomes prominent, it begins to affect translation and can result in positive selection for optimal codons. The positive selection can, in turn, significantly modulate codon preferences. PMID:23376453

  16. Using Food as a Tool to Teach Science to 3rd Grade Students in Appalachian Ohio

    ERIC Educational Resources Information Center

    Duffrin, Melani W.; Hovland, Jana; Carraway-Stage, Virginia; McLeod, Sara; Duffrin, Christopher; Phillips, Sharon; Rivera, David; Saum, Diana; Johanson, George; Graham, Annette; Lee, Tammy; Bosse, Michael; Berryman, Darlene

    2010-01-01

    The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. In 2007 to 2008, a foods curriculum developed by professionals in nutrition and education was implemented in 10 3rd-grade classrooms in Appalachian Ohio; teachers in these…

  17. PreK-3rd: What Is the Price Tag? Policy to Action Brief. No. 2

    ERIC Educational Resources Information Center

    Shore, Rima

    2009-01-01

    In an era of intense fiscal pressures, educators are focusing on those investments most likely to lift student achievement. They are also trying to make more strategic use of existing resources. To achieve these goals, a growing number of policymakers are considering integrated PreK-3rd approaches. Increasingly, they are recognizing that the first…

  18. Patient protection at risk in IEC 60601-1 3rd edition.

    PubMed

    Dybdahl, K

    2009-09-01

    Engineers developing medical electrical equipment in accordance with IEC 60601-1 3rd edition are in immediate need of short- and long-term solutions to avoid potentially hazardous designs as a result of misinterpretation of the requirements. Several options are described to ensure consistency and safety of devices. PMID:19852179

  19. Evaluation of the "Respect Not Risk" Firearm Safety Lesson for 3rd-Graders

    ERIC Educational Resources Information Center

    Liller, Karen D.; Perrin, Karen; Nearns, Jodi; Pesce, Karen; Crane, Nancy B.; Gonzalez, Robin R.

    2003-01-01

    The purpose of this study was to evaluate the MORE HEALTH "Respect Not Risk" Firearm Safety Lesson for 3rd-graders in Pinellas County, Florida. Six schools representative of various socioeconomic levels were selected as the test sites. Qualitative and quantitative data were collected. A total of 433 matched pretests/posttests were used to…

  20. 75 FR 34450 - Filing Dates for the Indiana Special Election in the 3rd Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ELECTION COMMISSION Filing Dates for the Indiana Special Election in the 3rd Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Indiana has scheduled a...

  1. Prediction of High School Dropout or Graduation from 3rd Grade Data.

    ERIC Educational Resources Information Center

    Lloyd, Dee Norman; Bleach, Gail

    Measures of background characteristics, school performance, and tested achievement were analyzed for four race-by-sex samples of 3rd graders who were known to have later become high school dropouts or graduates. Results showed that as early as five to eight years before leaving school, dropouts differed significantly from graduates in age, tested…

  2. AL State Profile. Alabama: Alabama High School Graduation Exam (AHSGE), 3rd Edition

    ERIC Educational Resources Information Center

    Center on Education Policy, 2010

    2010-01-01

    This paper provides information about Alabama High School Graduation Exam, 3rd Edition, a comprehensive standards-based exam. The purpose of the exam is to: (1) Provide schools with student academic diagnostic information; (2) Determine prospective high school graduates' mastery of the state curriculum; (3) Increase alignment of local curriculum…

  3. 16. 3RD FLOOR, J.M. LEHMANN CO. FIVEROLL TOILET SOAP MILL ...

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

    16. 3RD FLOOR, J.M. LEHMANN CO. FIVE-ROLL TOILET SOAP MILL INSTALLED 1950, TO WEST; BUCKET CONVEYOR AT RIGHT MOVED WASTE FROM 2ND FLOOR SOAP PRESSES TO 5TH FLOOR RE-MANUFACTURE - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  4. Linking Learning: The PreK-3rd Path to School Success

    ERIC Educational Resources Information Center

    Advocates for Children of New Jersey, 2010

    2010-01-01

    Giving children high-quality preschool is the first step in the journey to school success. The next steps--kindergarten through 3rd grade--are equally important. Advocates for Children of New Jersey (ACNJ) is working on several fronts to help school districts across the state build strong early learning programs, which can significantly improve…

  5. 78. VIEW OF 3RD TEE, TAKEN FROM SOUTHEAST SIDE OF ...

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

    78. VIEW OF 3RD TEE, TAKEN FROM SOUTHEAST SIDE OF PIER, FACING SOUTHWEST, SHOWING NORTHEAST SIDE OF THE TACKLE BOX (LEFT), SOUTHEAST SIDE AND NORTHEAST FRONT OF PUMPHOUSE (RIGHT), AND RESTROOMS IN BACKGROUND - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  6. Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

    PubMed Central

    Hudson, Nicholas J.; Gu, Quan; Nagaraj, Shivashankar H.; Ding, Yong-Sheng; Dalrymple, Brian P.; Reverter, Antonio

    2011-01-01

    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. PMID:21966531

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

    PubMed

    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. PMID:25623487

  8. An Investigation of the Relationship Between Retention in First Grade and Performance on High Stakes Tests in 3rd Grade

    PubMed Central

    Hughes, Jan N.; Chen, Qi; Thoemmes, Felix; Kwok, Oi-man

    2010-01-01

    The association between grade retention in first grade and passing the third grade state accountability tests, the Texas Assessment of Knowledge and Skills (TAKS) reading and math, was investigated in a sample of 769 students who were recruited into the study when they were in first grade. Of these 769 students, 165 were retained in first grade and 604 were promoted. Using propensity matching, we created five imputed datasets (average N=321) in which promoted and retained students were matched on 67 comprehensive covariates. Using GEE models, we obtained the association between retention and passing the 3rd grade TAKS reading and math tests. The positive association between retention and math scores was significant while the association was marginally significant for reading scores. PMID:20628547

  9. Modal Codon Usage: Assessing the Typical Codon Usage of a Genome

    PubMed Central

    Davis, James J.; Olsen, Gary J.

    2010-01-01

    Most genomes are heterogeneous in codon usage, so a codon usage study should start by defining the codon usage that is typical to the genome. Although this is commonly taken to be the genomewide average, we propose that the mode—the codon usage that matches the most genes—provides a more useful approximation of the typical codon usage of a genome. We provide a method for estimating the modal codon usage, which utilizes a continuous approximation to the number of matching genes and a simplex optimization. In a survey of bacterial and archaeal genomes, as many as 20% more of the genes in a given genome match the modal codon usage than the average codon usage. We use the mode to examine the evolution of the multireplicon genomes of Agrobacterium tumefaciens C58 and Borrelia burgdorferi B31. In A. tumefaciens, the circular and linear chromosomes are characterized by a common “chromosome-like” codon usage, whereas both plasmids share a distinct “plasmid-like” codon usage. In B. burgdorferi, in addition to different codon-usage biases on the leading and lagging strands of DNA replication found by McInerney (McInerney JO. 1998. Replicational and transcriptional selection on codon usage in Borrelia burgdorferi. Proc Natl Acad Sci USA. 95:10698–10703), we also detect a codon-usage similarity between linear plasmid lp38 and the leading strand of the chromosome and a high similarity among the cp32 family of plasmids. PMID:20018979

  10. Codon Usage Patterns in Corynebacterium glutamicum: Mutational Bias, Natural Selection and Amino Acid Conservation.

    PubMed

    Liu, Guiming; Wu, Jinyu; Yang, Huanming; Bao, Qiyu

    2010-01-01

    The alternative synonymous codons in Corynebacterium glutamicum, a well-known bacterium used in industry for the production of amino acid, have been investigated by multivariate analysis. As C. glutamicum is a GC-rich organism, G and C are expected to predominate at the third position of codons. Indeed, overall codon usage analyses have indicated that C and/or G ending codons are predominant in this organism. Through multivariate statistical analysis, apart from mutational selection, we identified three other trends of codon usage variation among the genes. Firstly, the majority of highly expressed genes are scattered towards the positive end of the first axis, whereas the majority of lowly expressed genes are clustered towards the other end of the first axis. Furthermore, the distinct difference in the two sets of genes was that the C ending codons are predominate in putatively highly expressed genes, suggesting that the C ending codons are translationally optimal in this organism. Secondly, the majority of the putatively highly expressed genes have a tendency to locate on the leading strand, which indicates that replicational and transciptional selection might be invoked. Thirdly, highly expressed genes are more conserved than lowly expressed genes by synonymous and nonsynonymous substitutions among orthologous genes fromthe genomes of C. glutamicum and C. diphtheriae. We also analyzed other factors such as the length of genes and hydrophobicity that might influence codon usage and found their contributions to be weak. PMID:20445740

  11. Correlates and Phenomenology of 1st and 3rd Person Memories

    PubMed Central

    Sutin, Angelina R.; Robins, Richard W.

    2010-01-01

    The present research addressed fundamental questions about the visual perspective of autobiographical memories: Are stable personality characteristics associated with visual perspective? Does visual perspective influence the memory's phenomenological qualities? Participants in Study 1 (N = 1,684) completed individual-difference measures and indicated the perspective from which they generally retrieve memories. Participants in Study 2 (N = 706) retrieved a memory from their natural or manipulated perspective, rated its phenomenology, and completed the same individual-difference measures. Dissociation and anxiety were associated with 3rd person retrieval style; the Big Five personality traits were primarily unrelated to perspective. Compared to 3rd person memories, naturally-occurring 1st person memories were higher on Vividness, Coherence, Accessibility, Sensory Detail, Emotional Intensity, and Time Perspective and lower on Distancing; manipulating perspective eliminated these differences. Visual perspective is associated with clinically-relevant constructs and, although associated with the memory's phenomenology, perspective does not shape it. PMID:20665336

  12. Conference report: the 3rd Global CRO Council for Bioanalysis at the International Reid Bioanalytical Forum.

    PubMed

    Breda, Massimo; Garofolo, Fabio; Caturla, Maria Cruz; Couerbe, Philippe; Maltas, John; White, Peter; Struwe, Petra; Sangster, Timothy; Riches, Suzanne; Hillier, Jim; Garofolo, Wei; Zimmerman, Thomas; Pawula, Maria; Collins, Eileen; Schoutsen, Dick; Wieling, Jaap; Green, Rachel; Houghton, Richard; Jeanbaptiste, Bernard; Claassen, Quinton; Harter, Tammy; Seymour, Mark

    2011-12-01

    The 3rd Global CRO Council Closed Forum was held on the 3rd and 4th July 2011 in Guildford, United Kingdom, in conjunction with the 19th International Reid Bioanalytical Forum. In attendance were 21 senior-level representatives from 19 CROs on behalf of nine European countries and, for many of the attendees, this occasion was the first time that they had participated in a GCC meeting. Therefore, this closed forum was an opportunity to increase awareness of the aim of the GCC and how it works, share information about bioanalytical regulations and audit findings from different agencies, their policies and procedures and also to discuss some topics of interest and aim to develop ideas and provide recommendations for bioanalytical practices at future GCC meetings in Europe. PMID:22185271

  13. 1st Central and Eastern European Proteomic Conference and 3rd Czech Proteomic Conference.

    PubMed

    Kovarova, Hana; Gadher, Suresh Jivan; Archakov, Alexander

    2008-02-01

    The 1st Central and Eastern European Proteomic Conference was organized together with the 3rd Czech Proteomic Conference in the TOP Hotel, Prague in the Czech Republic from the 29th to the 31st October, 2007. The aim was to strengthen links with scientists from Central and Eastern Europe including Russia, which until now have been weak or nonexistent, and to highlight the emergence of excellent proteomic studies from various countries, which until now were not visible. PMID:18282121

  14. Higher order modes of a 3rd harmonic cavity with an increased end-cup iris

    SciTech Connect

    T. Khabibouline; N. Solyak; R. Wanzenberg

    2003-05-19

    The cavity design for a 3rd harmonic cavity for the TTF 2 photoinjector has been revised to increase the coupling between the main coupler and the cavity cells. The iris radius of the end cup of the cavity has been increased to accomplish a better coupling. The basic rf-parameters and the higher order modes of the modified design are summarized in this report.

  15. What is FirstSchool? Issues in PreK-3rd Education. Number One

    ERIC Educational Resources Information Center

    Ritchie, Sharon; Maxwell, Kelly; Clifford, Richard

    2009-01-01

    FirstSchool is part of a national PreK-3rd movement of schools, districts, educators and universities seeking to improve how children from ages 3 to 8 learn and develop in schools. While these different projects use a variety of names, all are working to connect high-quality PreK programs with high-quality elementary schools. FirstSchool is…

  16. 13. Photocopy of 1920 drawing titled: BUILDING 78, 3RD FLOOR ...

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

    13. Photocopy of 1920 drawing titled: BUILDING 78, 3RD FLOOR BALCONY AND FIRE ESCAPES, including plans for skylight and North Elevation. HABS photograph is an 8x10' contact print made from a high contrast negative of an enlargement made from microfiche. Original is in the collection of Department of Public Works, Puget Sound Naval Shipyard, Bremerton, WA. - Puget Sound Naval Shipyard, Administration Building, Farragut Avenue, Bremerton, Kitsap County, WA

  17. Insights from the 3rd World Congress on Integrated Computational Materials Engineering

    NASA Astrophysics Data System (ADS)

    Howe, D.; Goodlet, B.; Weaver, J.; Spanos, G.

    2016-05-01

    The 3rd World Congress on Integrated Computational Materials Engineering (ICME) was a forum for presenting the "state-of-the-art" in the ICME discipline, as well as for charting a path for future community efforts. The event concluded with in an interactive panel-led discussion that addressed such topics as integrating efforts between experimental and computational scientists, uncertainty quantification, and identifying the greatest challenges for future workforce preparation. This article is a summary of this discussion and the thoughts presented.

  18. CLINICAL ASSESSMENT OF THE 1/3rd RADIUS USING A NEW DESKTOP ULTRASONIC BONE DENSITOMETER

    PubMed Central

    Stein, Emily M.; Rosete, Fernando; Young, Polly; Kamanda-Kosseh, Mafo; McMahon, Donald J.; Luo, Gangming; Kaufman, Jonathan J.; Shane, Elizabeth; Siffert, Robert S.

    2012-01-01

    The objectives of this study were to evaluate the capability of a novel ultrasound device to clinically estimate bone mineral density (BMD) at the 1/3rd radius. The device rests on a desktop and is portable, and permits real-time evaluation of the radial BMD. The device measures two (2) net time delay (NTD) parameters, NTDDW and NTDCW. NTDDW is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue, cortex and medullary cavity, and the transit time through soft tissue only of equal overall distance. NTDCW is defined as the difference between the transit time of an ultrasound pulse to travel through soft-tissue and cortex only, and the transit time through soft tissue only again of equal overall distance. The square root of the product of these two parameters is a measure of the radial BMD at the 1/3rd location as measured by dual-energy x-ray absorptiometry (DXA). A clinical IRB-approved study measured ultrasonically sixty adults at the 1/3rd radius. BMD was also measured at the same anatomical site and time using DXA. A linear regression using NTD produced a linear correlation coefficient of 0.93 (P<0.001). These results are consistent with previously reported simulation and in vitro studies. In conclusion, although x-ray methods are effective in bone mass assessment, osteoporosis remains one of the largest undiagnosed and under-diagnosed diseases in the world today. The research described here should enable significant expansion of diagnosis and monitoring of osteoporosis through a desktop device that ultrasonically assesses bone mass at the 1/3rd radius. PMID:23312957

  19. 3rd Workshop on Semantic Ambient Media Experience (SAME) - In Conjunction with AmI-2010

    NASA Astrophysics Data System (ADS)

    Lugmayr, Artur; Stockleben, Bjoern; Kaario, Juha; Pogorelc, Bogdan; Risse, Thomas

    The SAME workshop takes place for the 3rd time in 2010, and it's theme in this year was creating the business value-creation, vision, media theories and technology for ambient media. SAME differs from other workshops due to its interactive and creative touch and going beyond simple powerpoint presentations. Several results will be published by AMEA - the AMbient Media Association (www.ambientmediaassociation.org.

  20. The Goodrich 3rd generation DB-110 system: successful flight test on the F-16 aircraft

    NASA Astrophysics Data System (ADS)

    Lange, Davis; Iyengar, Mrinal; Maver, Larry; Dyer, Gavin; Francis, John

    2007-04-01

    The 3rd Generation Goodrich DB-110 system provides users with a three (3) field-of-view high performance Airborne Reconnaissance capability that incorporates a dual-band day and nighttime imaging sensor, a real time recording and a real time data transmission capability to support long range, medium range, and short range standoff and over-flight mission scenarios, all within a single pod. Goodrich developed their 3rd Generation Airborne Reconnaissance Pod for operation on a range of aircraft types including F-16, F-15, F-18, Euro-fighter and older aircraft such as the F-4, F-111, Mirage and Tornado. This system upgrades the existing, operationally proven, 2nd generation DB-110 design with enhancements in sensor resolution, flight envelope and other performance improvements. Goodrich recently flight tested their 3rd Generation Reconnaissance System on a Block 52 F-16 aircraft with first flight success and excellent results. This paper presents key highlights of the system and presents imaging results from flight test.

  1. Recent advances on developing 3rd generation enzyme electrode for biosensor applications.

    PubMed

    Das, Priyanki; Das, Madhuri; Chinnadayyala, Somasekhar R; Singha, Irom Manoj; Goswami, Pranab

    2016-05-15

    The electrochemical biosensor with enzyme as biorecognition element is traditionally pursued as an attractive research topic owing to their high commercial perspective in healthcare and environmental sectors. The research interest on the subject is sharply increased since the beginning of 21st century primarily, due to the concomitant increase in knowledge in the field of material science. The remarkable effects of many advance materials such as, conductive polymers and nanomaterials, were acknowledged in the developing efficient 3rd generation enzyme bioelectrodes which offer superior selectivity, sensitivity, reagent less detection, and label free fabrication of biosensors. The present review article compiles the major knowledge surfaced on the subject since its inception incorporating the key review and experimental papers published during the last decade which extensively cover the development on the redox enzyme based 3rd generation electrochemical biosensors. The tenet involved in the function of these direct electrochemistry based enzyme electrodes, their characterizations and various strategies reported so far for their development such as, nanofabrication, polymer based and reconstitution approaches are elucidated. In addition, the possible challenges and the future prospects in the development of efficient biosensors following this direct electrochemistry based principle are discussed. A comparative account on the design strategies and critical performance factors involved in the 3rd generation biosensors among some selected prominent works published on the subject during last decade have also been included in a tabular form for ready reference to the readers. PMID:26735873

  2. Codon preferences in free-living microorganisms.

    PubMed Central

    Andersson, S G; Kurland, C G

    1990-01-01

    A popular interpretation of the major codon preference is that it reflects the operation of a regulatory device that controls the expression of individual proteins. In this popular model, rapidly translated codons are thought to promote the accumulation of the highly expressed proteins and slowly translated codons are thought to retard the expression of poorly expressed proteins. However, this widely accepted model is not supported by kinetic theory or by experimental results. A less fashionable model in which the major codon preference has nothing to do with the expression level of the individual proteins is forwarded. In this model, the major codon preference is viewed as a global strategy to support the efficient function of the translation system and thereby to maximize the growth rates of cells under favorable conditions. PMID:2194095

  3. Codon information value and codon transition-probability distributions in short-term evolution

    NASA Astrophysics Data System (ADS)

    Jiménez-Montaño, M. A.; Coronel-Brizio, H. F.; Hernández-Montoya, A. R.; Ramos-Fernández, A.

    2016-07-01

    To understand the way the Genetic Code and the physical-chemical properties of coded amino acids affect accepted amino acid substitutions in short-term protein evolution, taking into account only overall amino acid conservation, we consider an underlying codon-level model. This model employs codon pair-substitution frequencies from an empirical matrix in the literature, modified for single-base mutations only. Ordering the degenerated codons according to their codon information value (Volkenstein, 1979), we found that three-fold and most of four-fold degenerated codons, which have low codon values, were best fitted to rank-frequency distributions with constant failure rate (exponentials). In contrast, almost all two-fold degenerated codons, which have high codon values, were best fitted to rank-frequency distributions with variable failure rate (inverse power-laws). Six-fold degenerated codons are considered to be doubly assigned. The exceptional behavior of some codons, including non-degenerate codons, is discussed.

  4. CodonPhyML: Fast Maximum Likelihood Phylogeny Estimation under Codon Substitution Models

    PubMed Central

    Gil, Manuel; Zoller, Stefan; Anisimova, Maria

    2013-01-01

    Markov models of codon substitution naturally incorporate the structure of the genetic code and the selection intensity at the protein level, providing a more realistic representation of protein-coding sequences compared with nucleotide or amino acid models. Thus, for protein-coding genes, phylogenetic inference is expected to be more accurate under codon models. So far, phylogeny reconstruction under codon models has been elusive due to computational difficulties of dealing with high dimension matrices. Here, we present a fast maximum likelihood (ML) package for phylogenetic inference, CodonPhyML offering hundreds of different codon models, the largest variety to date, for phylogeny inference by ML. CodonPhyML is tested on simulated and real data and is shown to offer excellent speed and convergence properties. In addition, CodonPhyML includes most recent fast methods for estimating phylogenetic branch supports and provides an integral framework for models selection, including amino acid and DNA models. PMID:23436912

  5. NURSING EMERGING. ANA Nursing: Scope and Standards of Practice, (2015) 3rd Edition.

    PubMed

    Mariano, Carla

    2016-04-01

    AHNA Past-President Carla Mariano recently had the privilege of serving on the American Nurses Association's (ANA) Nursing Scope and Standards Revision Workgroup. Representing the specialty practice of holistic nursing, Carla's presence within this workgroup contributed greatly to the inclusion of holistic principles and values throughout the new 2015 Nursing: Scope and Standards of Practice, 3rd edition, the foundational document that informs and guides professional nursing practice within the United States. This is a significant step forward for holistic nursing and an indicator of our growing influence as specialty practice. PMID:27305802

  6. Preface to Special Topic: Invited Papers of the 3rd International Conference on Ultrafast Structural Dynamics

    PubMed Central

    Johnson, S. L.

    2016-01-01

    The ability to visualize the real-time dynamics of atomic, magnetic, and electronic structure is widely recognized in many fields as a key element underpinning many important processes in chemistry, materials science, and biology. The need for an improved understanding of such processes becomes acute as energy conversion processes on fast time scales become increasingly relevant to problems in science and technology. This special issue, containing invited papers from participants at the 3rd International Conference on Ultrafast Structural Dynamics held June 10–12, 2015 in Zurich, Switzerland, discusses several recent developments in this area. PMID:27191008

  7. Preface to Special Topic: Invited Papers of the 3rd International Conference on Ultrafast Structural Dynamics.

    PubMed

    Johnson, S L

    2016-03-01

    The ability to visualize the real-time dynamics of atomic, magnetic, and electronic structure is widely recognized in many fields as a key element underpinning many important processes in chemistry, materials science, and biology. The need for an improved understanding of such processes becomes acute as energy conversion processes on fast time scales become increasingly relevant to problems in science and technology. This special issue, containing invited papers from participants at the 3rd International Conference on Ultrafast Structural Dynamics held June 10-12, 2015 in Zurich, Switzerland, discusses several recent developments in this area. PMID:27191008

  8. Overview of the 3rd isirv-Antiviral Group Conference – advances in clinical management

    PubMed Central

    Hurt, Aeron C; Hui, David S; Hay, Alan; Hayden, Frederick G

    2015-01-01

    This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference - advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted. PMID:25399715

  9. A global drought climatology for the 3rd edition of the World Atlas of Desertification (WAD)

    NASA Astrophysics Data System (ADS)

    Spinoni, Jonathan; Carrao, Hugo; Naumann, Gustavo; Antofie, Tiberiu; Barbosa, Paulo; Vogt, Jürgen

    2013-04-01

    A new version of the World Atlas of Desertification (WAD) is being compiled in the framework of cooperation between the Joint Research Centre (JRC) of the European Commission and the United Nations Environment Programme (UNEP). This initiative aims at mapping the global land degradation and desertification, as well as introducing the reader with complex interactions of geo-physical, socio-economic, and political aspects that affect the environmental sustainability. Recurrent extreme events resulting from climate change, such as more severe droughts, combined with non-adapted land use practices can affect the resilience of ecosystems tipping them into a less productive state. Thus, to describe the effects of climatological hazards on land degradation and desertification processes, we computed a World drought climatology that will be part of the 3rd edition of the WAD and will replace and update to 2010 the results presented in the 2nd edition in 1997. This paper presents the methodology used to compute three parameters included in the WAD drought climatology, i.e. drought frequency, intensity and duration, and discusses their spatio-temporal patterns both at global and continental scales. Because drought is mainly driven and triggered by a rainfall deficit, we chose the Standardized Precipitation Index (SPI) as the drought indicator to estimate our climatological parameters. The SPI is a statistical precipitation-based drought indicator widely used in drought-related studies. We calculated the SPI on three different accumulation periods: 3 months (SPI-3), 6 months (SPI-6), and 12 months (SPI-12), in order to take into account meteorological, agricultural, and hydrological drought-related features. Each quantity has been calculated on a monthly basis using the baseline period between January 1951 and December 2010. As data input, we used the Full Data Reanalysis Version 6.0 (0.5˚x0.5˚) of gridded monthly precipitation provided by the Global Precipitation

  10. Evolutionary characterization of Tembusu virus infection through identification of codon usage patterns.

    PubMed

    Zhou, Hao; Yan, Bing; Chen, Shun; Wang, Mingshu; Jia, Renyong; Cheng, Anchun

    2015-10-01

    Tembusu virus (TMUV) is a single-stranded, positive-sense RNA virus. As reported, TMUV infection has resulted in significant poultry losses, and the virus may also pose a threat to public health. To characterize TMUV evolutionarily and to understand the factors accounting for codon usage properties, we performed, for the first time, a comprehensive analysis of codon usage bias for the genomes of 60 TMUV strains. The most recently published TMUV strains were found to be widely distributed in coastal cities of southeastern China. Codon preference among TMUV genomes exhibits a low bias (effective number of codons (ENC)=53.287) and is maintained at a stable level. ENC-GC3 plots and the high correlation between composition constraints and principal component factor analysis of codon usage demonstrated that mutation pressure dominates over natural selection pressure in shaping the TMUV coding sequence composition. The high correlation between the major components of the codon usage pattern and hydrophobicity (Gravy) or aromaticity (Aromo) was obvious, indicating that properties of viral proteins also account for the observed variation in TMUV codon usage. Principal component analysis (PCA) showed that CQW1 isolated from Chongqing may have evolved from GX2013H or GX2013G isolated from Guangxi, thus indicating that TMUV likely disseminated from southeastern China to the mainland. Moreover, the preferred codons encoding eight amino acids were consistent with the optimal codons for human cells, indicating that TMUV may pose a threat to public health due to possible cross-species transmission (birds to birds or birds to humans). The results of this study not only have theoretical value for uncovering the characteristics of synonymous codon usage patterns in TMUV genomes but also have significant meaning with regard to the molecular evolutionary tendencies of TMUV. PMID:26205688

  11. Mutation and Selection Cause Codon Usage and Bias in Mitochondrial Genomes of Ribbon Worms (Nemertea)

    PubMed Central

    Chen, Haixia; Sun, Shichun; Norenburg, Jon L.; Sundberg, Per

    2014-01-01

    The phenomenon of codon usage bias is known to exist in many genomes and it is mainly determined by mutation and selection. To understand the patterns of codon usage in nemertean mitochondrial genomes, we use bioinformatic approaches to analyze the protein-coding sequences of eight nemertean species. Neutrality analysis did not find a significant correlation between GC12 and GC3. ENc-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENc values are below it. ENc-plot suggested 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 and we propose that codons containing A or U at third position are used preferentially in nemertean species, regardless of whether corresponding tRNAs are encoded in the mitochondrial DNA. Context-dependent analysis indicated that the nucleotide at the second codon position slightly affects synonymous codon choices. These results suggested that mutational and selection forces are probably acting to codon usage bias in nemertean mitochondrial genomes. PMID:24454907

  12. Mutation and selection cause codon usage and bias in mitochondrial genomes of ribbon worms (Nemertea).

    PubMed

    Chen, Haixia; Sun, Shichun; Norenburg, Jon L; Sundberg, Per

    2014-01-01

    The phenomenon of codon usage bias is known to exist in many genomes and it is mainly determined by mutation and selection. To understand the patterns of codon usage in nemertean mitochondrial genomes, we use bioinformatic approaches to analyze the protein-coding sequences of eight nemertean species. Neutrality analysis did not find a significant correlation between GC12 and GC3. ENc-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENc values are below it. ENc-plot suggested 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 and we propose that codons containing A or U at third position are used preferentially in nemertean species, regardless of whether corresponding tRNAs are encoded in the mitochondrial DNA. Context-dependent analysis indicated that the nucleotide at the second codon position slightly affects synonymous codon choices. These results suggested that mutational and selection forces are probably acting to codon usage bias in nemertean mitochondrial genomes. PMID:24454907

  13. Di-codon Usage for Gene Classification

    NASA Astrophysics Data System (ADS)

    Nguyen, Minh N.; Ma, Jianmin; Fogel, Gary B.; Rajapakse, Jagath C.

    Classification of genes into biologically related groups facilitates inference of their functions. Codon usage bias has been described previously as a potential feature for gene classification. In this paper, we demonstrate that di-codon usage can further improve classification of genes. By using both codon and di-codon features, we achieve near perfect accuracies for the classification of HLA molecules into major classes and sub-classes. The method is illustrated on 1,841 HLA sequences which are classified into two major classes, HLA-I and HLA-II. Major classes are further classified into sub-groups. A binary SVM using di-codon usage patterns achieved 99.95% accuracy in the classification of HLA genes into major HLA classes; and multi-class SVM achieved accuracy rates of 99.82% and 99.03% for sub-class classification of HLA-I and HLA-II genes, respectively. Furthermore, by combining codon and di-codon usages, the prediction accuracies reached 100%, 99.82%, and 99.84% for HLA major class classification, and for sub-class classification of HLA-I and HLA-II genes, respectively.

  14. Escherichia coli and Staphylococcus phages: effect of translation initiation efficiency on differential codon adaptation mediated by virulent and temperate lifestyles

    PubMed Central

    Prabhakaran, Ramanandan; Chithambaram, Shivapriya

    2015-01-01

    Rapid biosynthesis is key to the success of bacteria and viruses. Highly expressed genes in bacteria exhibit a strong codon bias corresponding to the differential availability of tRNAs. However, a large clade of lambdoid coliphages exhibits relatively poor codon adaptation to the host translation machinery, in contrast to other coliphages that exhibit strong codon adaptation to the host. Three possible explanations were previously proposed but dismissed: (1) the phage-borne tRNA genes that reduce the dependence of phage translation on host tRNAs, (2) lack of time needed for evolving codon adaptation due to recent host switching, and (3) strong strand asymmetry with biased mutation disrupting codon adaptation. Here, we examined the possibility that phages with relatively poor codon adaptation have poor translation initiation which would weaken the selection on codon adaptation. We measured translation initiation by: (1) the strength and position of the Shine–Dalgarno (SD) sequence, and (2) the stability of the secondary structure of sequences flanking the SD and start codon known to affect accessibility of the SD sequence and start codon. Phage genes with strong codon adaptation had significantly stronger SD sequences than those with poor codon adaptation. The former also had significantly weaker secondary structure in sequences flanking the SD sequence and start codon than the latter. Thus, lambdoid phages do not exhibit strong codon adaptation because they have relatively inefficient translation initiation and would benefit little from increased elongation efficiency. We also provided evidence suggesting that phage lifestyle (virulent versus temperate) affected selection intensity on the efficiency of translation initiation and elongation. PMID:25614589

  15. Treatment of 3rd molar-induced periodontal defects with guided tissue regeneration.

    PubMed

    Oxford, G E; Quintero, G; Stuller, C B; Gher, M E

    1997-07-01

    Recent reports provide evidence of increased attachment levels when using guided tissue regeneration (GTR) techniques for the treatment of periodontal defects. Periodontal defects frequently occur at the distal aspect of mandibular 2nd molars which are next to mesioangular impacted 3rd molars that have oral communication. The purpose of this study was to determine whether the use of GTR can enhance probing attachment levels (PALs) following extraction of mesioangular impacted third molars. 12 patients with bilateral soft tissue impacted mandibular 3rd molars entered this split mouth study. After extractions, the previously exposed distal root surface of the 2nd molars were debrided. The defects on the randomly selected experimental sites were covered with expanded polytetraflouro-ethylene (e-PTFE) membrane and the tissue was replaced to cover the membrane. Membranes were removed after 6 weeks. Control sites were treated identically except no membrane was placed. GI, P1I, PD, PAL and BOP records were obtained at 0, 3 and 6 months. The use of barrier material did not provide statistically-significant differences in PAL when comparing experimental versus control sites. Nevertheless, PAL gain was consistently greater at 3 and 6 months when GTR techniques were used in sites with deep impactions. PMID:9226386

  16. Using food as a tool to teach science to 3rd grade students in Appalachian Ohio

    PubMed Central

    Duffrin, Melani W.; Hovland, Jana; Carraway-Stage, Virginia; McLeod, Sara; Duffrin, Christopher; Phillips, Sharon; Rivera, David; Saum, Diana; Johanson, George; Graham, Annette; Lee, Tammy; Bosse, Michael; Berryman, Darlene

    2010-01-01

    The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. In 2007–2008, a foods curriculum developed by professionals in nutrition and education was implemented in 10 3rd-grade classrooms in Appalachian Ohio; teachers in these classrooms implemented 45 hands-on foods activities that covered 10 food topics. Subjects included measurement; food safety; vegetables; fruits; milk and cheese; meat, poultry, and fish; eggs; fats; grains; and meal management. Students in four other classrooms served as the control group. Mainstream 3rd-grade students were targeted because of their receptiveness to the subject matter, science standards for upper elementary grades, and testing that the students would undergo in 4th grade. Teachers and students alike reported that the hands-on FoodMASTER curriculum experience was worthwhile and enjoyable. Our initial classroom observation indicated that the majority of students, girls and boys included, were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. PMID:20975982

  17. Understanding discrimination by the ribosome: stability testing and groove measurement of codon-anticodon pairs.

    PubMed

    Sanbonmatsu, K Y; Joseph, S

    2003-04-18

    The ribosome must discriminate between correct and incorrect tRNAs with sufficient speed and accuracy to sustain an adequate rate of cell growth. Here, we report the results of explicit solvent molecular dynamics simulations, which address the mechanism of discrimination by the ribosome. The universally conserved 16S rRNA base A1493 and the kink in mRNA between A and P sites amplify differences in stability between cognate and near-cognate codon-anticodon pairs. Destabilization by the mRNA kink also provides a geometric explanation for the higher error rates observed for mismatches in the first codon position relative to mismatches in the second codon position. For more stable near-cognates, the repositioning of the universally conserved bases A1492 and G530 results in increased solvent exposure and an uncompensated loss of hydrogen bonds, preventing correct codon-anticodon-ribosome interactions from forming. PMID:12683995

  18. PREFACE: 3rd International Symposium on Functional Materials 2009 (ISFM 2009) 3rd International Symposium on Functional Materials 2009 (ISFM 2009)

    NASA Astrophysics Data System (ADS)

    Kiwon, Kim; Li, Lu; Taehyun, Nam; Jouhyeon, Ahn

    2010-05-01

    The 3rd International Symposium on Functional Materials 2009 (ISFM 2009) and its preconference, Advances in Functional Materials 2009 (AFM 2009), were successfully held in the Republic of Korea from 15-18 June 2009 and in the People's Republic of China from 8-12 June 2009, respectively. The two conferences attracted over 300 oral and poster presentations from over 12 countries including Australia, Canada, China, Germany, Japan, India, Israel, Korea, The Netherlands, Thailand, the UK and the USA. In the two conferences, eight keynote lectures were delivered by S Miyazaki, S A Akbar, D J Singh, C Suryanarayana, M~Greenblatt, H Zhang, T Sato and J Ding. This topical issue of Physica Scripta contains papers presented at the ISFM 2009 and AFM 2009. Keyan Li from Dalian University, People's Republic of China, presents some empirical formulae to estimate the elastic moduli of rocksalt-, zincblende- and chalcopyrite-structured crystals, on the basis of electronegativities of bonded atoms in the crystallographic frame. Min-Jung Kim from Hanyang University, Korea, reports on the preparation and characterization of carboxyl functionalization of magnetite nanoparticles for oligonucleotide immobilization. F Yan from the National University of Singapore studies the fabrication of Bi(Fe0.5Sc0.5)O3-PbTiO3 (BSF-PT) thin films by pulsed laser deposition, and the enhanced magnetic moment with respect to BiFeO3-PbTiO3. Dong-Gil Lee from Pusan National University, Korea, reports on the sterilization of enteropathogenic Escherichia coli using nanofiber TiO2 films prepared by the electrostatic spray method. Sang-Eun Park from the Korea Institute of Science and Technology reports on the study of encapsulated Fe3O4 nanoparticles with a silica thin layer with a reversible capacity of about 363 mAhg-1. Other researchers report on many other exiting achievements in the fields of ferromagnetic materials, magneto-optical materials, thermoelectric materials, shape memory materials, fuel-cell and

  19. Analysis of Codon Usage Patterns in Herbaceous Peony (Paeonia lactiflora Pall.) Based on Transcriptome Data.

    PubMed

    Wu, Yanqing; Zhao, Daqiu; Tao, Jun

    2015-01-01

    Codon usage bias, which exists in many genomes, is mainly determined by mutation and selection. To elucidate the genetic features and evolutionary history of herbaceous peony (Paeonia lactiflora), a well-known symbol of prosperity in China, we examined synonymous codon usage in 24,216 reconstructed genes from the P. lactiflora transcriptome. The mean GC content was 44.4%, indicating that the nucleotide content of P. lactiflora genes is slightly AT rich and GC poor. The P. lactiflora genome has a wide range of GC3 (GC content at the third synonymous codon position) distribution, with a significant correlation between GC12 and GC3. ENC (effective number of codons) analysis suggested that mutational bias played a major role in shaping codon usage. Parity Rule 2 (PR2) analysis revealed that GC and AU were not used proportionally. We identified 22 "optimal codons", most ending with an A or U. Our results suggested that nucleotide composition mutation bias and translational selection were the main driving factors of codon usage bias in P. lactiflora. These results lay the foundation for exploring the evolutionary mechanisms and heterologous expression of functionally-important proteins in P. lactiflora. PMID:26506393

  20. PREFACE: 3rd International Conference of Mechanical Engineering Research (ICMER 2015)

    NASA Astrophysics Data System (ADS)

    Mamat, Riazalman; Rahman, Mustafizur; Mohd. Zuki Nik Mohamed, Nik; Che Ghani, Saiful Anwar; Harun, Wan Sharuzi Wan

    2015-12-01

    The 3rd ICMER2015 is the continuity of the NCMER2010. The year 2010 represents a significant milestone in the history for Faculty of Mechanical Engineering, Universiti Malaysia Pahang (UMP) Malaysia with the organization of the first and second national level conferences (1st and 2nd NCMER) at UMP on May 26-27 and Dec 3-4 2010. The Faculty then changed the name from National Conference on Mechanical Engineering Research (NCMER) to International Conference on Mechanical Engineering Research (ICMER) in 2011 and this year, 2015 is our 3rd ICMER. These proceedings contain the selected scientific manuscripts submitted to the conference. It is with great pleasure to welcome you to the "International Conference on Mechanical Engineering Research (ICMER2015)" that is held at Zenith Hotel, Kuantan, Malaysia. The call for papers attracted submissions of over two hundred abstracts from twelve different countries including Japan, Iran, China, Kuwait, Indonesia, Norway, Philippines, Morocco, Germany, UAE and more. The scientific papers published in these proceedings have been revised and approved by the technical committee of the 3rd ICMER2015. All of the papers exhibit clear, concise, and precise expositions that appeal to a broad international readership interested in mechanical engineering, combustion, metallurgy, materials science as well as in manufacturing and biomechanics. The reports present original ideas or results of general significance supported by clear reasoning and compelling evidence, and employ methods, theories and practices relevant to the research. The authors clearly state the questions and the significance of their research to theory and practice, describe how the research contributes to new knowledge, and provide tables and figures that meaningfully add to the narrative. In this edition of ICMER representatives attending are from academia, industry, governmental and private sectors. The plenary and invited speakers will present, discuss, promote and

  1. Codon compression algorithms for saturation mutagenesis.

    PubMed

    Pines, Gur; Pines, Assaf; Garst, Andrew D; Zeitoun, Ramsey I; Lynch, Sean A; Gill, Ryan T

    2015-05-15

    Saturation mutagenesis is employed in protein engineering and genome-editing efforts to generate libraries that span amino acid design space. Traditionally, this is accomplished by using degenerate/compressed codons such as NNK (N = A/C/G/T, K = G/T), which covers all amino acids and one stop codon. These solutions suffer from two types of redundancy: (a) different codons for the same amino acid lead to bias, and (b) wild type amino acid is included within the library. These redundancies increase library size and downstream screening efforts. Here, we present a dynamic approach to compress codons for any desired list of amino acids, taking into account codon usage. This results in a unique codon collection for every amino acid to be mutated, with the desired redundancy level. Finally, we demonstrate that this approach can be used to design precise oligo libraries amendable to recombineering and CRISPR-based genome editing to obtain a diverse population with high efficiency. PMID:25303315

  2. The effect of context on synonymous codon usage in genes with low codon usage bias.

    PubMed Central

    Bulmer, M

    1990-01-01

    The effect of neighbouring bases on the usage of synonymous codons in genes with low codon usage bias in yeast and E. coli is examined. The codon adaptation index is employed to identify a group of genes in each organism with low codon usage bias, which are likely to be weakly expressed. A similar pattern is found in complementary sequences with respect to synonymous usage of A vs G or of U vs C. It is suggested that this may reflect an effect of context on mutation rates in weakly expressed genes. PMID:2190183

  3. Defining a new vision for the retinoblastoma gene: report from the 3rd International Rb Meeting.

    PubMed

    Rubin, Seth M; Sage, Julien

    2013-01-01

    The retinoblastoma tumor suppressor (Rb) pathway is mutated in most, if not all human tumors. In the G0/G1 phase, Rb and its family members p107 and p130 inhibit the E2F family of transcription factors. In response to mitogenic signals, Cyclin-dependent kinases (CDKs) phosphorylate Rb family members, which results in the disruption of complexes between Rb and E2F family members and in the transcription of genes essential for S phase progression. Beyond this role in early cell cycle decisions, Rb family members regulate DNA replication and mitosis, chromatin structure, metabolism, cellular differentiation, and cell death. While the RB pathway has been extensively studied in the past three decades, new investigations continue to provide novel insights into basic mechanisms of cancer development and, beyond cancer, help better understand fundamental cellular processes, from plants to mammals. This meeting report summarizes research presented at the recently held 3rd International Rb Meeting. PMID:24257515

  4. Defining a new vision for the retinoblastoma gene: report from the 3rd International Rb Meeting

    PubMed Central

    2013-01-01

    The retinoblastoma tumor suppressor (Rb) pathway is mutated in most, if not all human tumors. In the G0/G1 phase, Rb and its family members p107 and p130 inhibit the E2F family of transcription factors. In response to mitogenic signals, Cyclin-dependent kinases (CDKs) phosphorylate Rb family members, which results in the disruption of complexes between Rb and E2F family members and in the transcription of genes essential for S phase progression. Beyond this role in early cell cycle decisions, Rb family members regulate DNA replication and mitosis, chromatin structure, metabolism, cellular differentiation, and cell death. While the RB pathway has been extensively studied in the past three decades, new investigations continue to provide novel insights into basic mechanisms of cancer development and, beyond cancer, help better understand fundamental cellular processes, from plants to mammals. This meeting report summarizes research presented at the recently held 3rd International Rb Meeting. PMID:24257515

  5. Dental health in antique population of Vinkovci - Cibalae in Croatia (3rd-5th century).

    PubMed

    Peko, Dunja; Vodanović, Marin

    2016-08-01

    Roman city Cibalae (Vinkovci) - the birthplace of Roman emperors Valentinian I and Valens was a very well developed urban ares in the late antique what was evidenced by numerous archaeological findings. The aim of this paper is to get insight in dental health of antique population of Cibalae. One hundred individuals with 2041 teeth dated to 3rd - 5th century AD have been analyzed for caries, antemortem tooth loss, periapical diseases and tooth wear. Prevalence of antemortem tooth loss was 4.3% in males, 5.2% in females. Prevalence of caries per tooth was 8.4% in males, 7.0% in females. Compared to other Croatian antique sites, ancient inhabitants of Roman Cibalae had rather good dental health with low caries prevalence and no gender differences. Statistically significant difference was found between males in females in the prevalence of periapical lesions and degree of tooth wear. Periapical lesions were found only in males. PMID:27598951

  6. Passive solar progress: a simplified guide to the 3rd national passive solar conference

    SciTech Connect

    Miller, H.; Howell, Y.; Richards, D.

    1980-10-01

    Some of the concepts and practices that have come to be known as passive solar heating and cooling are introduced, and a current picture of the field is presented. Much of the material presented is derived from papers given at the 3rd National Passive Solar Conference held in San Jose, California in January 1979 and sponsored by the US Department of Energy. Extracts and data from these papers have been integrated in the text with explanatory and descriptive material. In this way, it is attempted to present technical information in an introductory context. Topics include design considerations, passive and hybrid systems and applications, sizing methods and performance prediction, and implementation issues. A glossary is included. (WHK)

  7. John D. Rockefeller 3rd, statesman and founder of the Population Council.

    PubMed

    Dunlop, J

    2000-01-01

    This article presents a profile of John D. Rockefeller 3rd, statesman and founder of the Population Council. It is noted that Rockefeller took a broad view of population control as a means to address poverty and economic development rather than as an end in itself. In 1952 he initiated the convocation of the Conference on Population Problems held in Williamsburg, Virginia. The discussion focused on food supply, industrial development, depletion of natural resources, and political instability resulting from unchecked population growth. In 1967, Rockefeller initiated, lobbied for, and finally achieved a World Leaders' Statement signed by 30 heads of state including US President Lyndon Johnson. The document drew attention to population growth as a world problem and engendered political support for family planning as a solution. After 3 years the Commission on Population Growth and the American Future was established, and Rockefeller was made its chairman. Several issues were debated, including more safer fertility control and the legalization of abortion. PMID:12349764

  8. Cotranslational insertion of selenocysteine into formate dehydrogenase from Escherichia coli directed by a UGA codon

    SciTech Connect

    Zinoni, F.; Birkmann, A.; Leinfelder, W.; Boeck, A.

    1987-05-01

    The structural gene (fdhF) for the 80-kDa selenopolypeptide of formate dehydrogenase from Escherichia coli contains an in-frame UGA codon at amino acid position 140 that is translated. Translation of gene fusions between N-terminal parts of fdhF with lacZ depends on the availability of selenium in the medium when the hybrid gene contains the UGA codon; it is independent of the presence of selenium when an fdhF portion upstream of the UGA position is fused to lacZ. Transcription does not require the presence of selenium in either case. By localized mutagenesis, the UGA codon was converted into serine (UCA) and cysteine (UGC and UGU) codons. Each mutagion relieved the selenium dependency of fdhF mRNA translation. Selenium incorporation was completely abolished in the case of the UCA insertion and was reduced to about 10% when the UGA was replaced by a cysteine codon. Insertion of UCA yielded an inactive fdhF gene product, while insertion of UGC and UGU resulted in polypeptides with lowered activities as components in the system formerly known as formate hydrogenlyase. Altogether the results indicate that the UGA codon at position 140 directs the cotranslational insertion of selenocysteine into the fdhF polypeptide chain.

  9. Detection and clinical evolution of scrapie in sheep by 3rd eyelid biopsy.

    PubMed

    Vargas, Francisco; Luján, Lluís; Bolea, Rosa; Monleón, Eva; Martín-Burriel, Inmaculada; Fernández, Antonio; De Blas, Ignacio; Badiola, Juan José

    2006-01-01

    The goal of this article was to characterize the clinical evolution of scrapie in naturally affected sheep. Eighteen sheep with scrapie diagnosed by examination of 3rd eyelid biopsy and 12 control ewes were studied throughout the duration of their disease. Diagnosis was confirmed postmortem by histopathologic, immunohistochemical, and Western blot analysis of nervous tissue. Complete clinical examinations were performed every 2 weeks for each animal, of which 3 clinical examinations per animal are reported. Those clinical signs that showed a significant frequency within the corresponding clinical examination were considered representative of each stage of the disease (ie, early, middle, and late). The representative clinical signs for the early stage were hypoesthesia in the limbs, alteration of mental status, and a body condition score <3. Remarkably, hypoesthesia in the limbs was one of the 1st signs appearing during the early clinical stage in the affected animals, even before the appearance of other signs. For the middle stage, representative signs were the same as those for the early stage, together with hyporreflexia in the limbs, cardiac arrhythmia, pruritus/wool loss, and the appearance of the nibbling reflex. Representative clinical signs for the late stage were the same as those for the early and middle stage, together with head tremors, hyperexcitability to external stimuli, ataxia or gait abnormalities, and teeth grinding. On the basis of these results, we propose the calculation of an objective clinical index that allows the differentiation among clinical stages and that could be useful for further studies. The usefulness of 3rd eyelid lymphoid tissue biopsies for sequential clinical studies in naturally scrapie-affected sheep is demonstrated. PMID:16496940

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

    PubMed

    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. PMID:26544153

  11. To keep the catch – that is the question: a personal account of the 3rd Annual EULAR Congress, Stockholm

    PubMed Central

    Wollheim, Frank A

    2002-01-01

    The 3rd Annual EULAR Congress, held in Stockholm on 12–15 June 2002, had a turnout of 8300 delegates, almost identical to last year's record attendance level in Prague. The venue was close to ideal, allowing ample space for poster sessions in the exhibition hall. The manned poster sessions were well attended, even on the last day of the Congress. The numerous invited speakers represented the world's elite, allowing the staging of excellent state-of-the-art podium sessions. The aim of attracting the young scientific community was partly achieved, but individual delegates' dependence on industry sponsorship poses potential problems. The organization was a big improvement compared to that of the two previous congresses. Approximately 1800 abstracts were submitted, an increase of 50%, resulting in a higher quality of accepted abstracts. The satellite symposia held every morning and late afternoon were well attended; thus, industry exposure of new products, both in podium sessions and at the exhibitions, was well accommodated. The Annual EULAR Congress consolidates its position as one of the two most important annual congresses of rheumatology, but EULAR economy and commercial aspects are still too dominant in relation to science. PMID:12223107

  12. Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons.

    PubMed Central

    Berry, M J; Banu, L; Harney, J W; Larsen, P R

    1993-01-01

    We investigated the requirements for selenocysteine insertion at single or multiple UGA codons in eukaryotic selenoproteins. Two functional SECIS elements were identified in the 3' untranslated region of the rat selenoprotein P mRNA, with predicted stem-loops and critical nucleotides similar to those in the SECIS elements in the type I iodothyronine 5' deiodinase (5'DI) and glutathione peroxidase selenoprotein mRNAs. Site-directed mutational analyses of three SECIS elements confirmed that conserved nucleotides in the loop and in unpaired regions of the stem are critical for activity. This indicates that multiple contact sites are required for SECIS function. Stop codon function at any of five out-of-context UGA codons in the 5'DI mRNA was suppressed by SECIS elements from the 5'DI or selenoprotein P genes linked downstream. Thus, the presence of SECIS elements in eukaryotic selenoprotein mRNAs permits complete flexibility in UGA codon position. Images PMID:8344267

  13. SENCA: A Multilayered Codon Model to Study the Origins and Dynamics of Codon Usage.

    PubMed

    Pouyet, Fanny; Bailly-Bechet, Marc; Mouchiroud, Dominique; Guéguen, Laurent

    2016-01-01

    Gene sequences are the target of evolution operating at different levels, including the nucleotide, codon, and amino acid levels. Disentangling the impact of those different levels on gene sequences requires developing a probabilistic model with three layers. Here we present SENCA (site evolution of nucleotides, codons, and amino acids), a codon substitution model that separately describes 1) nucleotide processes which apply on all sites of a sequence such as the mutational bias, 2) preferences between synonymous codons, and 3) preferences among amino acids. We argue that most synonymous substitutions are not neutral and that SENCA provides more accurate estimates of selection compared with more classical codon sequence models. We study the forces that drive the genomic content evolution, intraspecifically in the core genome of 21 prokaryotes and interspecifically for five Enterobacteria. We retrieve the existence of a universal mutational bias toward AT, and that taking into account selection on synonymous codon usage has consequences on the measurement of selection on nonsynonymous substitutions. We also confirm that codon usage bias is mostly driven by selection on preferred codons. We propose new summary statistics to measure the relative importance of the different evolutionary processes acting on sequences. PMID:27401173

  14. SENCA: A Multilayered Codon Model to Study the Origins and Dynamics of Codon Usage

    PubMed Central

    Pouyet, Fanny; Bailly-Bechet, Marc; Mouchiroud, Dominique; Guéguen, Laurent

    2016-01-01

    Gene sequences are the target of evolution operating at different levels, including the nucleotide, codon, and amino acid levels. Disentangling the impact of those different levels on gene sequences requires developing a probabilistic model with three layers. Here we present SENCA (site evolution of nucleotides, codons, and amino acids), a codon substitution model that separately describes 1) nucleotide processes which apply on all sites of a sequence such as the mutational bias, 2) preferences between synonymous codons, and 3) preferences among amino acids. We argue that most synonymous substitutions are not neutral and that SENCA provides more accurate estimates of selection compared with more classical codon sequence models. We study the forces that drive the genomic content evolution, intraspecifically in the core genome of 21 prokaryotes and interspecifically for five Enterobacteria. We retrieve the existence of a universal mutational bias toward AT, and that taking into account selection on synonymous codon usage has consequences on the measurement of selection on nonsynonymous substitutions. We also confirm that codon usage bias is mostly driven by selection on preferred codons. We propose new summary statistics to measure the relative importance of the different evolutionary processes acting on sequences. PMID:27401173

  15. When should orthostatic blood pressure changes be evaluated in elderly: 1st, 3rd or 5th minute?

    PubMed

    Soysal, Pinar; Aydin, Ali Ekrem; Koc Okudur, Saadet; Isik, Ahmet Turan

    2016-01-01

    Detection of orthostatic hypotension (OH) is very important in geriatric practice, since OH is associated with mortality, ischemic stroke, falls, cognitive failure and depression. It was aimed to determine the most appropriate time for measuring blood pressure in transition from supine to upright position in order to diagnose OH in elderly. Comprehensive geriatric assessment (CGA) including Head up Tilt Table (HUT) test was performed in 407 geriatric patients. Orthostatic changes were assessed separately for the 1st, 3rd and 5th minutes (HUT1, HUT3 and HUT5, respectively) taking the data in supine position as the basis. The mean age, recurrent falls, presence of dementia and Parkinson's disease, number of drugs, alpha-blocker and anti-dementia drug use, and fasting blood glucose levels were significantly higher in the patients with versus without OH; whereas, albumin and 25-hydroxy vitamin D levels were significantly lower (p<0.05). However, different from HUT3 and HUT5, Charlson Comorbidity Index and the prevalence of diabetes mellitus were higher, the use of antidiabetics, antipsychotics, benzodiazepine, opioid and levodopa were more common (p<0.05). Statistical significance of the number of drugs and fasting blood glucose level was prominent in HUT1 as compared to HUT3 (p<0.01, p<0.05). Comparison of the patients that had OH only in HUT1, HUT3or HUT5 revealed no difference in terms of CGA parameters. These results suggests that orthostatic blood pressure changes determined at the 1st minute might be more important for geriatric practice. Moreover, 1st minute measurement might be more convenient in the elderly as it requires shorter time in practice. PMID:27077324

  16. Effect of non-erupted 3rd molars on distal roots and supporting structures of approximal teeth. A radiographic survey of 202 cases.

    PubMed

    Nemcovsky, C E; Libfeld, H; Zubery, Y

    1996-09-01

    Root resorption of 2nd molars in proximity to non-erupted 3rd molars has been widely reported. The purpose of this study was to determine the prevalence of root resorption in second molars adjacent to non-erupted third molars. Its association to age and gender of the patient, location and inclination of the non-erupted third molar and to distal bone support of the 2nd molars was analyzed. A radiographic survey of 202 periapical radiographs taken in patients with clinically missing third molars was conducted. 3 examiners independently evaluated the radiographs and only those cases where at least 2 observers agreed were included in this report. Statistical analysis was performed on 186 radiographs. Associations were analyzed with the Pearson chi 2 test. Radiographic evidence of root resorption was found in 45 2nd molars (24.2%) of which 12 (6.5%) showed moderate to complete root resorption. Non-erupted tooth apical position and mesio-inclination of 60 degrees or more relative to the distal root of the second molar were significantly associated with root resorption (p = 0.01368 and p = 0.0194, respectively). Resorption was positively associated with age of patient (p = 0.00606). These results may support early extraction of impacted 3rd molars especially in cases with a mesio-angulation of 60 degrees or more and an apical location in proximity to the distal root of the 2nd molar. PMID:8891930

  17. The 3^rd International Conference on Women in Physics: Global Perspectives, Common Concerns, Worldwide Views

    NASA Astrophysics Data System (ADS)

    Zastavker, Yevgeniya V.

    2009-03-01

    The 3^rd International Conference on Women in Physics (ICWIP), held in Seoul, Korea, in October 2008, brought together 300 participants from 57 countries, including a diverse 22-member U.S. Delegation, for a 3-day summit of stimulating discussions, thought-provoking presentations, inspirational posters, and networking. Held under the auspices of the Working Group on Women in Physics of the International Union of Pure and Applied Physics (IUPAP), this meeting built on the successes of the 1^st (Paris, 2002) and 2^nd (Rio de Janeiro, 2005) Conferences and further clarified the importance of diversifying the field of physics worldwide. Although considerable progress has been made since 2002, it was clear that the global scientific workforce is still under-utilizing a large percentage of the available female talent pool. If human society is to benefit to its fullest from various contributions that the field of physics can offer in addressing global issues of economic crisis, energy, environment, water, health, poverty, and hunger, women of all races and nationalities need to become fully included and engaged in the national and international physical community. To address these and many other issues, the ICWIP unanimously approved a five-part resolution to IUPAP recommending actions to promote the recruitment, retention, and advancement of women in physics and related fields.

  18. Effects of notetaking instruction on 3rd grade student's science learning and notetaking behavior

    NASA Astrophysics Data System (ADS)

    Lee, Pai-Lin

    The research examined effects of notetaking instruction on elementary-aged students' ability to recall science information and notetaking behavior. Classes of 3rd grade students were randomly assigned to three treatment conditions, strategic notetaking, partial strategic notetaking, and control, for 4 training sessions. The effects of the notetaking instruction were measured by their performances on a test on science information taught during the training, a long-term free recall of the information, and number of information units recalled with or without cues. Students' prior science achievement was used to group students into two levels (high vs. low) and functioned as another independent variable in analysis. Results indicated significant treatment effect on cued and non-cued recall of the information units in favor of the strategy instruction groups. Students with higher prior achievement in science performed better on cued recall and long-term free recall of information. The results suggest that students as young as at the third grade can be instructed to develop the ability of notetaking that promotes their learning.

  19. Resurgence of duckweed research and applications: report from the 3rd International Duckweed Conference.

    PubMed

    Appenroth, Klaus-J; Sree, K Sowjanya; Fakhoorian, Tamra; Lam, Eric

    2015-12-01

    Duckweed, flowering plants in the Lemnaceae family, comprises the smallest angiosperms in the plant kingdom. They have some of the fastest biomass accumulation rates reported to date for plants and have the demonstrated ability to thrive on wastewater rich in dissolved organic compounds and thus could help to remediated polluted water resources and prevents eutrophication. With a high quality genome sequence now available and increased commercial interest worldwide to develop duckweed biomass for renewables such as protein and fuel, the 3rd International Duckweed Conference convened at Kyoto, Japan, in July of 2015, to update the community of duckweed researchers and developers on the progress in the field. In addition to sharing results and ideas, the conference also provided ample opportunities for new-comers as well as established workers in the field to network and create new aliances. We hope this meeting summary will also help to disseminate the key advances and observations that have been presented in this conference to the broader plant biology community in order to encourage increased cross-fertilization of ideas and technologies. PMID:26506824

  20. Measuring the cascade rate in anisotropic turbulence through 3rd order structure functions.

    NASA Astrophysics Data System (ADS)

    Verdini, Andrea; Landi, Simone; Hellinger, Petr

    2014-05-01

    We employ the Von-Karman-Howart-Yaglom-Politano-Poquet (KHYPP)law, to compute the cascade rate by means of 3rd order structure functions in homogeneous, forced, DNS at high resolution. We consider first the isotropic case (no guide field) and verify that the cascade rate is consistent with the dissipation rate. Then we consider an anisotropic case (with guide field) for which the isotropic KHYPP law does not apply. We compute the parallel and perpendicular cascade rates and find that the latter basically accounts for the total dissipation rate, as expected for anisotropic turbulence. Also, the cascade rate derived from the isotropic law is found to be a good approximation for the total cascade rate. Recent works have shown that the hypothesis of stationary turbulence must be probably relaxed in the solar wind. We present preliminary results on the measure of the cascade rate in the expanding solar wind, obtained with DNS of MHD turbulence in the expanding box model. Such model incorporates the basic physic of expansion thus inducing anisotropies driven by both the magnetic field and expansion, along with an energy decrease due to the conservation of linear invariants (angular momentum and magnetic flux). The correction due to non-stationary conditions is found to be important and to become negligible only at small scales, thus suggesting that solar wind measurements over- estimate the actual cascade rate.

  1. Visual, Critical, and Scientific Thinking Dispositions in a 3rd Grade Science Classroom

    NASA Astrophysics Data System (ADS)

    Foss, Stacy

    Many American students leave school without the required 21st century critical thinking skills. This qualitative case study, based on the theoretical concepts of Facione, Arheim, and Vygotsky, explored the development of thinking dispositions through the arts in science on the development of scientific thinking skills when used as a conceptual thinking routine in a rural 3rd grade classroom. Research questions examined the disposition to think critically through the arts in science and focused on the perceptions and experiences of 25 students with the Visual Thinking Strategy (VTS) process. Data were collected from classroom observations (n = 10), student interviews (n = 25), teacher interviews ( n = 1), a focus group discussion (n = 3), and artifacts of student work (n = 25); these data included perceptions of VTS, school culture, and classroom characteristics. An inductive analysis of qualitative data resulted in several emergent themes regarding disposition development and students generating questions while increasing affective motivation. The most prevalent dispositions were open-mindedness, the truth-seeking disposition, the analytical disposition, and the systematicity disposition. The findings about the teachers indicated that VTS questions in science supported "gradual release of responsibility", the internalization of process skills and vocabulary, and argumentation. This case study offers descriptive research that links visual arts inquiry and the development of critical thinking dispositions in science at the elementary level. A science curriculum could be developed, that emphasizes the development of thinking dispositions through the arts in science, which in turn, could impact the professional development of teachers and learning outcomes for students.

  2. SESAME, A 3rd Generation Synchrotron Light Source for the Middle East

    SciTech Connect

    Einfeld, D.; Hasnain, S.S.; Sayers, Z.; Schopper, H.; Winick, H.; Al-Dmour, E.

    2004-05-12

    Developed under the auspices of UNESCO, SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) will be a major international research centre in the Middle East and Mediterranean region. On 6th of January 2003, the official foundation of SESAME took place. The facility is located in Allan, Jordan, 30 km North-West of Amman. As of August 2003 the Founding Members are Bahrain, Egypt, Iran, Israel, Jordan, Pakistan, Palestine, Turkey and United Arabic Emirates, representing a population of over 300 million. SESAME will be a 2.5 GeV 3rd Generation light source (emittance 24.6 nm.rad, circumference {approx}125m). About 40% of the circumference is available for insertion devices (average length 2.75m) in 13 straight sections. Beam lines are up to 36m. The site and a building are provided by Jordan. Construction started in August 2003. The scientific program will start with up to 6 beam lines: MAD Protein Crystallography, SAXS and WAXS for polymers and proteins, Powder Diffraction for material science, UV/VUV/SXR Photoelectron Spectroscopy and Photoabsorption Spectroscopy, IR Spectroscopy, and EXAFS.

  3. Albion: cost-effective 3rd generation high-performance thermal imaging in the UK

    NASA Astrophysics Data System (ADS)

    McEwen, R. K.; Lupton, M.; Lawrence, M.; Knowles, P.; Wilson, M.; Dennis, P. N. J.; Gordon, N. T.; Lees, D. J.; Parsons, J. F.

    2006-09-01

    The first generation of high performance thermal imaging sensors in the UK was based on two axis opto-mechanical scanning systems and small (4-16 element) arrays of the SPRITE detector, developed during the 1970s. Almost two decades later, a 2nd Generation system, STAIRS C was introduced, based on single axis scanning and a long linear array of approximately 3000 elements. This paper addresses the development of the UK's 3rd Generation High Performance Thermal Imaging sensor systems, under a programme known as "Albion". Three new high performance detectors, manufactured in cadmium mercury telluride, operating in both MWIR and LWIR, providing high resolution and sensitivities without need for opto-mechanical scanning systems will be described. The CMT material is grown by MOVPE on low cost substrates and bump bonded to the silicon read out circuit (ROIC). All three detectors are designed to fit with existing standard Integrated Detector Cooling Assemblies (IDCAs). The two largest detectors will be integrated with field demonstrator cameras providing MWIR and LWIR solutions that can rapidly be tailored to specific military requirements. The remaining detector will be a LWIR device with a smart ROIC, facilitating integration times much longer than can typically be achieved with focal plane arrays and consequently yield very high thermal sensitivity. This device will be demonstrated in a lab based camera system.

  4. Albion: the UK 3rd generation high-performance thermal imaging programme

    NASA Astrophysics Data System (ADS)

    McEwen, R. K.; Lupton, M.; Lawrence, M.; Knowles, P.; Wilson, M.; Dennis, P. N. J.; Gordon, N. T.; Lees, D. J.; Parsons, J. F.

    2007-04-01

    The first generation of high performance thermal imaging sensors in the UK was based on two axis opto-mechanical scanning systems and small (4-16 element) arrays of the SPRITE detector, developed during the 1970s. Almost two decades later, a 2nd Generation system, STAIRS C was introduced, based on single axis scanning and a long linear array of approximately 3000 elements. The UK has now begun the industrialisation of 3 rd Generation High Performance Thermal Imaging under a programme known as "Albion". Three new high performance cadmium mercury telluride arrays are being manufactured. The CMT material is grown by MOVPE on low cost substrates and bump bonded to the silicon read out circuit (ROIC). To maintain low production costs, all three detectors are designed to fit with existing standard Integrated Detector Cooling Assemblies (IDCAs). The two largest focal planes are conventional devices operating in the MWIR and LWIR spectral bands. A smaller format LWIR device is also described which has a smart ROIC, enabling much longer stare times than are feasible with conventional pixel circuits, thus achieving very high sensitivity. A new reference surface technology for thermal imaging sensors is described, based on Negative Luminescence (NL), which offers several advantages over conventional peltier references, improving the quality of the Non-Uniformity Correction (NUC) algorithms.

  5. SESAME-A 3rd Generation Synchrotron Light Source for the Middle East

    NASA Astrophysics Data System (ADS)

    Winick, Herman

    2010-02-01

    Developed under the auspices of UNESCO and modeled on CERN, SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) is an international research center in construction in Jordan. It will enable world class research by scientists from the region, reversing the brain drain. It will also build bridges between diverse societies, contributing to a culture of peace through international cooperation in science. The centerpiece is a synchrotron light source originating from BESSY I, a gift by Germany. The upgraded machine, a 2.5 GeV 3rd Generation Light Source (133m circumference, 26nm-rad emittance and 12 places for insertion devices), will provide light from infra-red to hard X-rays, offering excellent opportunities to train local scientists and attract those working abroad to return. The SESAME Council meets twice each year and presently has nine Members (Bahrain, Cyprus, Egypt, Iran, Israel, Jordan, Pakistan, Palestinian Authority, Turkey). Members have responsibility for the project and provide the annual operations budget (1.5M US dollars in 2009, expected to rise to about 5M when operation starts in 2012-13). Jordan provided the site, building, and infrastructure. A staff of 20 is installing the 0.8 GeV BESSY I injection system. The facility will have the capacity to serve 30 or more experiments operating simultaneously. See www.sesame.org.jo )

  6. Report from the 3rd AIDS Impact Conference: culture, community, empowerment.

    PubMed

    Aggleton, P

    1997-10-01

    Presentations made at the 3rd AIDS Impact Conferences in June 1997 in Melbourne, Australia are summarized. The presentations focused on the importance of local beliefs, practices, and sexual cultures as factors that impact HIV risk. The three dominant themes of this conference were a concern for community, an emphasis on culture, and empowerment for the most vulnerable groups. Speakers illustrated the importance of culture as a factor in the form, context, and meaning of sex among young men and women in Thailand, Australia, Italy, Cambodia, and the United States. Studies conducted in correctional facilities illustrate how the culture of sex and substance use can intensify the HIV risk. Papers examined the sexual revolution in China and the experiences of indigenous people in Brazil, Australia, and New Zealand. The presentations also highlighted drug use cultures among gay men in Australian and German cities and introduced new research methodologies for the analysis of these processes and issues. The closing presentation considered the politics of HIV and their relationship to national and international processes of negative societal responses to HIV diseases. PMID:11364796

  7. PREFACE: 3rd International Conference on Manufacturing, Optimization, Industrial and Material Engineering (MOIME 2015)

    NASA Astrophysics Data System (ADS)

    Lumban Gaol, Ford; Webb, Jeff; Ding, Jun

    2015-05-01

    The 3rd International Conference on Manufacturing, Optimization, Industrial and Material Engineering (MOIME 2015) was held at the Sheraton Kuta, Bali, Indonesia, from 28 - 29 March 2015. The MOIME 2015 conference is aimed to bring together researchers, engineers and scientists in the domain of interest from around the world. MOIME 2015 is placed on promoting interaction between the theoretical, experimental, and applied communities, so that a high level exchange is achieved in new and emerging areas within Material Engineering, Industrial Engineering and all areas that relate to Optimization. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program, as well as the invited and plenary speakers. This year, we received 99 papers and after rigorous review, 24 papers were accepted. The participants come from eight countries. There were four parallel sessions and two invited speakers. It is an honour to present this volume of IOP Conference Series: Materials Science and Engineering (MSE) and we deeply thank the authors for their enthusiastic and high-grade contributions. Finally, we would like to thank the conference chairmen, the members of the steering committee, the organizing committee, the organizing secretariat and the financial support from the conference sponsors that allowed the success of MOIME 2015. The Editors of the MOIME 2015 Proceedings Dr. Ford Lumban Gaol Jeff Webb, Ph.D Prof. Jun DING, Ph.D

  8. Effect of 3rd-degree gravity harmonics and Earth perturbations on lunar artificial satellite orbits

    NASA Astrophysics Data System (ADS)

    Tzirti, S.; Tsiganis, K.; Varvoglis, H.

    2010-12-01

    In a previous work we studied the effects of (I) the J 2 and C 22 terms of the lunar potential and (II) the rotation of the primary on the critical inclination orbits of artificial satellites. Here, we show that, when 3rd-degree gravity harmonics are taken into account, the long-term orbital behavior and stability are strongly affected, especially for a non-rotating central body, where chaotic or collision orbits dominate the phase space. In the rotating case these phenomena are strongly weakened and the motion is mostly regular. When the averaged effect of the Earth’s perturbation is added, chaotic regions appear again for some inclination ranges. These are more important for higher values of semi-major axes. We compute the main families of periodic orbits, which are shown to emanate from the ‘frozen eccentricity’ and ‘critical inclination’ solutions of the axisymmetric problem (‘ J 2 + J 3’). Although the geometrical properties of the orbits are not preserved, we find that the variations in e, I and g can be quite small, so that they can be of practical importance to mission planning.

  9. Hand gesture recognition by analysis of codons

    NASA Astrophysics Data System (ADS)

    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.

  10. New half-film method for measuring Al2O3 film MTF of 3rd generation image intensifier

    NASA Astrophysics Data System (ADS)

    Cheng, Yaojin; Shi, Feng; Bai, Xiaofeng; Zhu, Yufeng; Yan, Lei; Liu, Feng; Li, Min

    2012-10-01

    In 3rd generation image intensifier, Al2O3 film on the input of MCP is a serious influence factor on device MTF due to its electron scattering process. There are no reportes about how to measure the MTF of Al2O3 film. In this paper a new Half-film comparssion test method is creatively established for determing the film MTF, which overcomes the difficulty of measuring super thin film less than a few nm. In this way, the MTF curves of 10nm Al2O3 film can be accurately obtained. The measurement results show that 10nm Al2O3 film obviously decay the MTF performance of the 3rd generation image intensifier and take an important role in the improvement work of 3rd generation image intensifier MTF and resolution performances.

  11. DHX29 reduces leaky scanning through an upstream AUG codon regardless of its nucleotide context

    PubMed Central

    Pisareva, Vera P.; Pisarev, Andrey V.

    2016-01-01

    During eukaryotic translation initiation, the 43S preinitiation complex (43S PIC), consisting of the 40S ribosomal subunit, eukaryotic initiation factors (eIFs) and initiator tRNA scans mRNA to find an appropriate start codon. Key roles in the accuracy of initiation codon selection belong to eIF1 and eIF1A, whereas the mammalian-specific DHX29 helicase substantially contributes to ribosomal scanning of structured mRNAs. Here, we show that DHX29 stimulates the recognition of the AUG codon but not the near-cognate CUG codon regardless of its nucleotide context during ribosomal scanning. The stimulatory effect depends on the contact between DHX29 and eIF1A. The unique DHX29 N-terminal domain binds to the ribosomal site near the mRNA entrance, where it contacts the eIF1A OB domain. UV crosslinking assays revealed that DHX29 may rearrange eIF1A and eIF2α in key nucleotide context positions of ribosomal complexes. Interestingly, DHX29 impedes the 48S initiation complex formation in the absence of eIF1A perhaps due to forming a physical barrier that prevents the 43S PIC from loading onto mRNA. Mutational analysis allowed us to split the mRNA unwinding and codon selection activities of DHX29. Thus, DHX29 is another example of an initiation factor contributing to start codon selection. PMID:27067542

  12. Analysis of Codon Usage Patterns in Herbaceous Peony (Paeonia lactiflora Pall.) Based on Transcriptome Data

    PubMed Central

    Wu, Yanqing; Zhao, Daqiu; Tao, Jun

    2015-01-01

    Codon usage bias, which exists in many genomes, is mainly determined by mutation and selection. To elucidate the genetic features and evolutionary history of herbaceous peony (Paeonia lactiflora), a well-known symbol of prosperity in China, we examined synonymous codon usage in 24,216 reconstructed genes from the P. lactiflora transcriptome. The mean GC content was 44.4%, indicating that the nucleotide content of P. lactiflora genes is slightly AT rich and GC poor. The P. lactiflora genome has a wide range of GC3 (GC content at the third synonymous codon position) distribution, with a significant correlation between GC12 and GC3. ENC (effective number of codons) analysis suggested that mutational bias played a major role in shaping codon usage. Parity Rule 2 (PR2) analysis revealed that GC and AU were not used proportionally. We identified 22 “optimal codons”, most ending with an A or U. Our results suggested that nucleotide composition mutation bias and translational selection were the main driving factors of codon usage bias in P. lactiflora. These results lay the foundation for exploring the evolutionary mechanisms and heterologous expression of functionally-important proteins in P. lactiflora. PMID:26506393

  13. Codon usage biases of transposable elements and host nuclear genes in Arabidopsis thaliana and Oryza sativa.

    PubMed

    Jia, Jia; Xue, Qingzhong

    2009-12-01

    Transposable elements (TEs) are mobile genetic entities ubiquitously distributed in nearly all genomes. High frequency of codons ending in A/T in TEs has been previously observed in some species. In this study, the biases in nucleotide composition and codon usage of TE transposases and host nuclear genes were investigated in the AT-rich genome of Arabidopsis thaliana and the GC-rich genome of Oryza sativa. Codons ending in A/T are more frequently used by TEs compared with their host nuclear genes. A remarkable positive correlation between highly expressed nuclear genes and C/G-ending codons were detected in O. sativa (r=0.944 and 0.839, respectively, P<0.0001) but not in A. thaliana, indicating a close association between the GC content and gene expression level in monocot species. In both species, TE codon usage biases are similar to that of weakly expressed genes. The expression and activity of TEs may be strictly controlled in plant genomes. Mutation bias and selection pressure have simultaneously acted on the TE evolution in A. thaliana and O. sativa. The consistently observed biases of nucleotide composition and codon usage of TEs may also provide a useful clue to accurately detect TE sequences in different species. PMID:20172490

  14. DHX29 reduces leaky scanning through an upstream AUG codon regardless of its nucleotide context.

    PubMed

    Pisareva, Vera P; Pisarev, Andrey V

    2016-05-19

    During eukaryotic translation initiation, the 43S preinitiation complex (43S PIC), consisting of the 40S ribosomal subunit, eukaryotic initiation factors (eIFs) and initiator tRNA scans mRNA to find an appropriate start codon. Key roles in the accuracy of initiation codon selection belong to eIF1 and eIF1A, whereas the mammalian-specific DHX29 helicase substantially contributes to ribosomal scanning of structured mRNAs. Here, we show that DHX29 stimulates the recognition of the AUG codon but not the near-cognate CUG codon regardless of its nucleotide context during ribosomal scanning. The stimulatory effect depends on the contact between DHX29 and eIF1A. The unique DHX29 N-terminal domain binds to the ribosomal site near the mRNA entrance, where it contacts the eIF1A OB domain. UV crosslinking assays revealed that DHX29 may rearrange eIF1A and eIF2α in key nucleotide context positions of ribosomal complexes. Interestingly, DHX29 impedes the 48S initiation complex formation in the absence of eIF1A perhaps due to forming a physical barrier that prevents the 43S PIC from loading onto mRNA. Mutational analysis allowed us to split the mRNA unwinding and codon selection activities of DHX29. Thus, DHX29 is another example of an initiation factor contributing to start codon selection. PMID:27067542

  15. Optimal codons in Tremella fuciformis end in C/G, a strong difference with known Tremella species.

    PubMed

    Deng, Youjin; Huang, Xiaoxing; Ruan, Banzhan; Xie, Baogui; van Peer, Arend Frans; Jiang, Yuji

    2015-11-01

    Tremella fuciformis is a popular edible fungus with fruiting bodies that can be produced in large quantities at low costs, while it is easy to transform and cultivate as yeast. This makes it an attractive potential bioreactor. Enhanced heterologous gene expression through codon optimization would be useful, but until now codon usage preferences in T. fuciformis remain unknown. To precisely determine the preferred codon usage of T. fuciformis we sequenced the genome of strain Tr26 resulting in a 24.2 Mb draft genome with 10,040 predicted genes. 3288 of the derived predicted proteins matched the UniProtKB/Swiss-Prot databases with 40% or more similarity. Corresponding gene models of this subset were subsequently optimized through repetitive comparison of alternative start codons and selection of best length matching gene models. For experimental confirmation of gene models, 96 random clones from an existing T. fuciformis cDNA library were sequenced, generating 80 complete CDSs. Calculated optimal codons for the 3288 predicted and the 80 cloned CDSs were highly similar, indicating sufficient accuracy of predicted gene models for codon usage analysis. T. fuciformis showed a strong preference for C and then G at the third base pair position of used codons, while average GC content of predicted genes was slightly higher than the total genome sequence average. Most optimal codons ended in C or G except for one, and an increased frequency of C ending codons was observed in genes with higher expression levels. Surprisingly, the preferred codon usage in T. fuciformis strongly differed from T. mesenterica and C. neoformans. Instead, optimal codon usage was similar to more distant related species such as Ustilago maydis and Neurospora crassa. Despite much higher overall sequence homology between T. fuciformis and T. mesenterica, only 7 out of 21 optimal codons were equal, whereas T. fuciformis shared up to 20 out of 21 optimal codons with other species. Clearly, codon usage in

  16. Role of GC-biased mutation pressure on synonymous codon choice in Micrococcus luteus, a bacterium with a high genomic GC-content.

    PubMed Central

    Ohama, T; Muto, A; Osawa, S

    1990-01-01

    The GC (G + C, or G or C)-contents of codon silent positions in all two-codon sets and three codons AUY/A (IIe), and in most of the family boxes of Micrococcus luteus (genomic GC-content: 74%) are 95% to 100% in both the highly and weakly expressed genes. In some family boxes, there is a decrease in NNC codons and an increase in NNG codons from the highly expressed to weakly expressed genes without apparent involvement of NNU and NNA codons. From these observations, we conclude that the selective use of synonymous codons in M. luteus may be largely determined by GC-biased mutation pressure and that in the highly expressed genes tRNAs would act as a weak selection pressure in some family boxes. Available data suggest that the effect of selection pressure by tRNAs on the synonymous codon choice becomes more apparent in the highly expressed genes in eubacteria with intermediate GC-contents such as Escherichia coli and Bacillus subtilis, and that the U/C ratio of the codon third positions in NNU/C-type two-codon sets in the weakly expressed genes would represent the approximate magnitude of directional mutation pressure throughout eubacteria. PMID:2326195

  17. The Power of PreK-3rd: How a Small Foundation Helped Push Washington State to the Forefront of the PreK-3rd Movement. FCD Case Study

    ERIC Educational Resources Information Center

    Nyhan, Paul

    2011-01-01

    The New School Foundation was not born from a commission, legislative mandate, research project, think tank, or even the mind of a leading education scholar. One of Washington state's pioneering PreK-3rd initiatives began as the brainchild of a wealthy Seattle businessman, Stuart Sloan, 20 years ago. The New School Foundation and its ideas were…

  18. 3rd hand smoking; heterogeneous oxidation of nicotine and secondary aerosol formation in the indoor environment

    NASA Astrophysics Data System (ADS)

    Petrick, Lauren; Dubowski, Yael

    2010-05-01

    Tobacco smoking is well known as a significant source of primary indoor air pollutants. However, only recently has it been recognized that the impact of Tobacco smoking may continue even after the cigarette has been extinguished (i.e., third hand smoke) due to the effect of indoor surfaces. These surfaces may affect the fate of tobacco smoke in the form of secondary reactions and pollutants, including secondary organic aerosol (SOA) formation. Fourier Transform Infrared spectrometry with Attenuated Total Reflection (FTIR-ATR) in tandem with a Scanning Mobility Particle Sizing (SMPS) system was used to monitor the ozonation of cellulose sorbed nicotine and resulting SOA formation. SOA formation began at onset of ozone introduction ([O3] = 60 ± 5 ppb) with a size distribution of dp ≤ 25 nm, and was determined to be a result of heterogeneous reaction (opposed to homogeneous). SOA yield from reacted surface nicotine was on the order of 10 %. Simultaneous to SOA monitoring, FTIR-ATR spectra showed surface changes in the nicotine film as the reaction progressed, revealing a pseudo first-order surface reaction rate of 0.0026 ± 0.0008 min-1. Identified surface oxidation products included: cotinine, myosmine, methylnicotinamide and nicotyrine. Surface reaction rate was found to be partially inhibited at high relative humidity. Given the toxicity of some of the identified products (e.g., cotinine has shown potential mutagenicity and teratogenicity) and that small particles may contribute to adverse health effects, the present study indicates that exposure to 3rd hand smoke ozonation products may pose additional health risks.

  19. Catalysis in the 3rd Dimension: How Organic Molecules May be Formed

    NASA Technical Reports Server (NTRS)

    Freund, Friedemann; DeVincenzi, D. (Technical Monitor)

    2001-01-01

    Catalysis is often little more than a word to phenomenologically describe the fact that a reaction follows a pat1 that leads to products of an unexpected kind or of unexpected yield. Low activation energy barriers for intermediates are recognized as the most likely cause why a system deviates from the thermodynamic pull towards minimizing its free energy and ends up in a metastable state. Seldom is the mechanism known. This i: particularly true for heterogeneous catalysis under hydrothermal conditions with minerals as catalysts. It is commonly assumed that catalytic action takes place across solid-fluid interfaces and that, on the atomic level, interfaces are just 2-dimensional contacts. This makes it difficult to understand, for instance, the assembly of long-chain carboxylic (fatty) acids. 3y studying single crystals that grew from a melt in the presence of H2O and CO2, we can show: (1) that numerals take up the fluid components into solid solution, (2) that some-thing happens converting them to -educedH and C, (3) that C atoms segregate into dislocations and tie C-C bonds. The products are medium-to-long chain Cn protomolecules, with some C-H attached, pre-assembled in the dislocations. Upon solvent extraction, these proto-molecules turn into carboxylic and dicarboxylic acids. This observation suggests that, in a very elementary step, catalysis under hydrothermal conditions leading to fatty acids involves the pre-assembly of Cn entities in the interface that is not 2-D but extends into the 3rd dimension, with dislocations as synthesis sites.

  20. PREFACE: 3rd International Youth Conference "Interdisciplinary Problems of Nanotechnology, Biomedicine and Nanotoxicology" (Nanobiotech 2015)

    NASA Astrophysics Data System (ADS)

    Refsnes, Magne, Prof; Gusev, Alexander, Dr; Godymchuk, Anna, Dr; Bogdan, Anna

    2015-11-01

    The 3rd International Youth Conference "Interdisciplinary Problems of Nanotechnology, Biomedicine and Nanotoxicology" (Nanobiotech2015) was held on 21-22 May 2015 in Tambov, Russia, and was jointly organized by Tambov Derzhavin State University (Russia), the Norwegian Institute of Public Health (Norway), the National University of Science and Technology MISiS (Russia), Tomsk Polytechnic University (Russia) and Tomsk State University. The conference gathered experienced and young researchers, post-docs and students, working in the fieldof nanotechnologies, nanomedicine, nano(eco)toxicology and risk assessment of nanomaterials, in order to facilitate the aggregation and sharing of interests and results for better collaboration and visibility of activity. The goal of Nanobiotech2015 was to bring researchers and practitioners together to share the latest knowledge on nanotechnology-specific risks to occupational and environmental health and assessing how to reduce these potential risks. The main objective of the conference is to identify, systematize and solve current scientific problems inthe sphere of nanobiotechnologies, nanomedicine and nanotoxicology, in order to join forces todetermine prospective areas and compose working groups of interested co-workers for carrying out interdisciplinary research projects. The topics of Nanobiotech2015 were: (1) Nanotechnologies in pharmaceutics and medicine; (2) Sources and mechanisms of nanoparticle release into the environment; (3) Ecological and biological effects of nanoparticles; (4) (Eco)toxicology of nanomaterials; (5) Methods for detection of nanoparticles in the environment and in biological objects; and (6) Physico-chemical properties of nanoparticles in the environment. We want to thank the Organizing Committee, the universities and sponsors supporting the conference,and everyone who contributed to the organization of this meeting, for their contribution towards the conference and for their contributions to these

  1. Codon catalog usage and the genome hypothesis.

    PubMed Central

    Grantham, R; Gautier, C; Gouy, M; Mercier, R; Pavé, A

    1980-01-01

    Frequencies for each of the 61 amino acid codons have been determined in every published mRNA sequence of 50 or more codons. The frequencies are shown for each kind of genome and for each individual gene. A surprising consistency of choices exists among genes of the same or similar genomes. Thus each genome, or kind of genome, appears to possess a "system" for choosing between codons. Frameshift genes, however, have widely different choice strategies from normal genes. Our work indicates that the main factors distinguishing between mRNA sequences relate to choices among degenerate bases. These systematic third base choices can therefore be used to establish a new kind of genetic distance, which reflects differences in coding strategy. The choice patterns we find seem compatible with the idea that the genome and not the individual gene is the unit of selection. Each gene in a genome tends to conform to its species' usage of the codon catalog; this is our genome hypothesis. PMID:6986610

  2. Test Review: C. Keith Conners "Conners 3rd Edition" Toronto, Ontario, Canada--Multi-Health Systems, 2008

    ERIC Educational Resources Information Center

    Kao, Grace S.; Thomas, Hillary M.

    2010-01-01

    "Conners 3rd Edition" is the most updated version of a series of measures for assessing attention deficit hyperactivity disorder (ADHD) and common comorbid problems/disorders in children and adolescents ranging from 6 to 18 years of age. Related problems that the test helps assess include executive dysfunction, learning problems, aggression, and…

  3. Exemplary Institute. Proceedings of the Annual Conference (3rd, Albuquerque, New Mexico, February 22-24, 1998).

    ERIC Educational Resources Information Center

    Native American Scholarship Fund, Inc., Albuquerque, NM.

    This proceedings contains presentations and workshop summaries from the 3rd Annual Exemplary Institute for educators of Native American students. Presentations include: "Quality in Learning: Romancing the Journey" (quality management at Mount Edgecumbe High School, Alaska) (Todd Bergman); "Creating a School-wide Literacy Climate" (Sig Boloz); "How…

  4. Constancy and Variability: Dialogic Literacy Events as Sites for Improvisation in Two 3rd-Grade Classrooms

    ERIC Educational Resources Information Center

    Jordan, Michelle E.; Santori, Diane

    2015-01-01

    This multisite study investigates dialogic literacy events that revolved around narrative and informational texts in two 3rd-grade classrooms. The authors offer a metaphor of musical improvisation to contemplate dialogic literacy events as part of the repertoire of teaching and learning experiences. In literacy learning, where there is much…

  5. 3rd Annual PIALA Conference Saipan--Collecting, Preserving & Sharing Information in Micronesia. Conference Proceedings. October 13-15, 1993.

    ERIC Educational Resources Information Center

    Edmundson, Margaret, Ed.

    1993-01-01

    This PIALA 1993 Proceedings contains many of the papers presented at the 3rd annual conference of the Pacific Islands Association of Libraries and Archives. This publication is the first time papers from this Micronesian regional library and archives conference have ever been published. The conference addressed various topics of interest to…

  6. Predicting 3rd Grade and 10th Grade FCAT Success for 2007-08. Research Brief. Volume 0702

    ERIC Educational Resources Information Center

    Froman, Terry; Rubiera, Vilma

    2008-01-01

    For the past few years the Florida School Code has set the Florida Comprehensive Assessment Test (FCAT) performance requirements for promotion of 3rd graders and graduation for 10 graders. Grade 3 students who do not score at level 2 or higher on the FCAT SSS Reading must be retained unless exempted for special circumstances. Grade 10 students…

  7. Predicting 3rd Grade and 10th Grade FCAT Success for 2006-07. Research Brief. Volume 0601

    ERIC Educational Resources Information Center

    Froman, Terry; Rubiera, Vilma

    2006-01-01

    For the past few years the Florida School Code has set the Florida Comprehensive Assessment Test (FCAT) performance requirements for promotion of 3rd graders and graduation for 10th graders. Grade 3 students who do not score at level 2 or higher on the FCAT SSS Reading must be retained unless exempted for special circumstances. Grade 10 students…

  8. The Lived Experiences of 3rd Generation and beyond U.S.-Born Mexican Heritage College Students: A Qualitative Study

    ERIC Educational Resources Information Center

    Galvan, Richard

    2011-01-01

    The purpose of this study was to describe the psychosocial and identity challenges of 3rd generation and beyond U.S.-born (3GAB-USB) Mexican heritage college students. Alvarez (1973) has written about the psychosocial impact "hybridity" can have on a U.S.- born (USB) Mexican individual who incorporates two distinct cultures (American and Mexican)…

  9. Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developmental Origins of Health and Disease (DOHaD) focuses on the earliest stages of human development, and provides a novel paradigm to complement other strategies for lifelong prevention of common chronic health conditions. The 3rd International Congress on DOHaD, held in 2005, retained the most ...

  10. Iowa Acceleration Scale Manual: A Guide for Whole-Grade Acceleration K-8. (3rd Edition, Manual)

    ERIC Educational Resources Information Center

    Assouline, Susan G.; Colangelo, Nicholas; Lupkowski-Shoplik, Ann; Forstadt, Leslie; Lipscomb, Jonathon

    2009-01-01

    Feedback from years of nationwide use has resulted in a 3rd Edition of this unique, systematic, and objective guide to considering and implementing academic acceleration. Developed and tested by the Belin-Blank Center at the University of Iowa, the IAS ensures that acceleration decisions are systematic, thoughtful, well reasoned, and defensible.…

  11. Visual Arts Teaching in Kindergarten through 3rd-Grade Classrooms in the UAE: Teacher Profiles, Perceptions, and Practices

    ERIC Educational Resources Information Center

    Buldu, Mehmet; Shaban, Mohamed S.

    2010-01-01

    This study portrayed a picture of kindergarten through 3rd-grade teachers who teach visual arts, their perceptions of the value of visual arts, their visual arts teaching practices, visual arts experiences provided to young learners in school, and major factors and/or influences that affect their teaching of visual arts. The sample for this study…

  12. Iron metabolism in African American women during the 2nd and 3rd trimester of a high-risk pregnancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To examine iron metabolism during the 2nd and 3rd trimester in African American women classified as a high-risk pregnancy. Design: Longitudinal. Setting: Large, university-based, urban Midwestern medical center. Participants: Convenience sample of 47 African American women classified a...

  13. Does 3rd Age + 3rd World = 3rd Class?

    ERIC Educational Resources Information Center

    Tout, Ken

    1992-01-01

    Demographic changes, migration, and industrialization are having drastic effects on older adults in developing nations. Local programs such as Pro Vida in Colombia, supported by Help Age International, rely on the support of volunteers to improve the quality of life for elderly people. (SK)

  14. PREFACE: 3rd International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS 2012)

    NASA Astrophysics Data System (ADS)

    Tayurskii, Dmitrii; Abe, Sumiyoshi; Alexandre Wang, Q.

    2012-11-01

    The 3rd International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS2012) was held between 25-30 August at Kazan (Volga Region) Federal University, Kazan, Russian Federation. This workshop was jointly organized by Kazan Federal University and Institut Supérieur des Matériaux et Mécaniques Avancées (ISMANS), France. The series of SPMCS workshops was created in 2008 with the aim to be an interdisciplinary incubator for the worldwide exchange of innovative ideas and information about the latest results. The first workshop was held at ISMANS, Le Mans (France) in 2008, and the third at Huazhong Normal University, Wuhan (China) in 2010. At SPMCS2012, we wished to bring together a broad community of researchers from the different branches of the rapidly developing complexity science to discuss the fundamental theoretical challenges (geometry/topology, number theory, statistical physics, dynamical systems, etc) as well as experimental and applied aspects of many practical problems (condensed matter, disordered systems, financial markets, chemistry, biology, geoscience, etc). The program of SPMCS2012 was prepared based on three categories: (i) physical and mathematical studies (quantum mechanics, generalized nonequilibrium thermodynamics, nonlinear dynamics, condensed matter physics, nanoscience); (ii) natural complex systems (physical, geophysical, chemical and biological); (iii) social, economical, political agent systems and man-made complex systems. The conference attracted 64 participants from 10 countries. There were 10 invited lectures, 12 invited talks and 28 regular oral talks in the morning and afternoon sessions. The book of Abstracts is available from the conference website (http://www.ksu.ru/conf/spmcs2012/?id=3). A round table was also held, the topic of which was 'Recent and Anticipated Future Progress in Science of Complexity', discussing a variety of questions and opinions important for the understanding of the concept of

  15. Building monument materials during the 3rd-4rd millennium (Portugal)

    NASA Astrophysics Data System (ADS)

    Moita, Patricia; Pedro, Jorge; Boaventura, Rui; Mataloto, Rui; Maximo, Jaime; Almeida, Luís; Nogueira, Pedro

    2014-05-01

    Dolmens are the most conspicuous remains of the populations of the 4th and first half of 3rd millennia BCE. These tombs are impressive not only for their monumentality, but also because of the socioeconomic investment they represent for those Neolithic communities, namely from the Central-South of Portugal, who built them. Although dolmens have been studied for their funerary content and typologies, an interdisciplinary approach toward the geological characterization and sourcing of stones used in these constructions has not received enough attention from researchers. With MEGAGEO project a multidisciplinary group of geologist and archaeologists intends to assess the relationship between the distribution of dolmens in Central-South Portugal, their source materials, and the geological landscape. GIS will map the information gathered and will be used to analyse these relationships. The selection of the areas, with distinctive geologies (limestone vs granite), will allow to verify if human patterns of behaviour regarding the selection of megaliths are similar or different regionally. Geologically the first target area (Freixo, Alentejo) is dominated by a small intrusion of gabbro mingled/mixed within a granodioritic intrusion both related with variscan orogeny. Granodiorite exhibit several enclaves of igneous and metamorphic nature attesting the interaction between both igneous rocks as well with enclosing gneisses. Despite Alentejo region have a reduced number of outcrops the granodiorite provides rounded to tabular metric blocks. The gabbro is very coarse grained, sometimes with a cumulate texture, and their fracturing and weathering provide very fresh tabular blocks. The five studied dolmens (Quinta do Freixo #1 to #5) are implanted in a large granodioritic intrusion, around the gabbroic rocks, within an area of approximately 9km2. The medium grained granodiorite is ubiquity in all the dolmens slabs and occasionally it can be observed features of mixing and

  16. SESAME — A 3rd Generation Synchrotron Light Source for the Middle East

    NASA Astrophysics Data System (ADS)

    Å°lkü, Dinçer; Rahighi, Javad; Winick, Herman

    2007-01-01

    SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) will be the Middle East's first international research center. It is a cooperative venture by the scientists and governments of the region with founding members Bahrain, Egypt, Israel, Jordan, Pakistan, Palestine Authority, and Turkey. Iran is in the process of finalizing its formal membership. Other countries (Cyprus, Morocco, and the United Arab Emirates) are also expected to join. The permanent Council of member states has full responsibility for the project. Members provide the annual operating budget. Observer countries are Germany, Greece, Italy, Kuwait, Portugal, Russian Federation, Sweden, the UK, and the US. SESAME is being developed under the umbrella of UNESCO. Jordan was selected as the building site. SESAME will offer excellent opportunities for training of Middle East scientists and attract those working abroad to consider returning. SESAME will be a 2.5GeV 3rd Generation light source (emittance 26nm-rad, circumference ˜133m), providing excellent performance for structural molecular biology, molecular environmental science, surface and interface science, microelectromechanical devices, x-ray imaging, archaeological microanalysis, and materials characterization. It will cover a broad spectral range from the infrared to hard x-rays and will have 12 straight sections for insertion devices (average length 2.75m). The injector will be the BESSY I 0.8 GeV booster synchrotron which has been given as a gift from Germany. Four committees advise the Council and assist in developing the technical design, beam lines, user community, and scientific Program. The SESAME building, now in construction with funds and a site provided by Jordan, is scheduled for completion in late 2006 after which the BESSY I injector will be installed. First stored beam in the new 2.5 GeV ring is planned for 2009 with six initial beamlines planned. Some beamlines will be built by member countries

  17. SESAME - A 3rd Generation Synchrotron Light Source for the Middle East

    NASA Astrophysics Data System (ADS)

    U˝Lkü, Dinçer; Rahighi, Javad; Winick, Herman

    2007-01-01

    SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) will be the Middle East's first international research center. It is a cooperative venture by the scientists and governments of the region with founding members Bahrain, Egypt, Israel, Jordan, Pakistan, Palestine Authority, and Turkey. Iran is in the process of finalizing its formal membership. Other countries (Cyprus, Morocco, and the United Arab Emirates) are also expected to join. The permanent Council of member states has full responsibility for the project. Members provide the annual operating budget. Observer countries are Germany, Greece, Italy, Kuwait, Portugal, Russian Federation, Sweden, the UK, and the US. SESAME is being developed under the umbrella of UNESCO. Jordan was selected as the building site. SESAME will offer excellent opportunities for training of Middle East scientists and attract those working abroad to consider returning. SESAME will be a 2.5GeV 3rd Generation light source (emittance 26nm-rad, circumference ~133m), providing excellent performance for structural molecular biology, molecular environmental science, surface and interface science, microelectromechanical devices, x-ray imaging, archaeological microanalysis, and materials characterization. It will cover a broad spectral range from the infrared to hard x-rays and will have 12 straight sections for insertion devices (average length 2.75m). The injector will be the BESSY I 0.8 GeV booster synchrotron which has been given as a gift from Germany. Four committees advise the Council and assist in developing the technical design, beam lines, user community, and scientific Program. The SESAME building, now in construction with funds and a site provided by Jordan, is scheduled for completion in late 2006 after which the BESSY I injector will be installed. First stored beam in the new 2.5 GeV ring is planned for 2009 with six initial beamlines planned. Some beamlines will be built by member countries

  18. Essential surgery: key messages from Disease Control Priorities, 3rd edition.

    PubMed

    Mock, Charles N; Donkor, Peter; Gawande, Atul; Jamison, Dean T; Kruk, Margaret E; Debas, Haile T

    2015-05-30

    The World Bank will publish the nine volumes of Disease Control Priorities, 3rd edition, in 2015-16. Volume 1--Essential Surgery--identifies 44 surgical procedures as essential on the basis that they address substantial needs, are cost effective, and are feasible to implement. This report summarises and critically assesses the volume's five key findings. First, provision of essential surgical procedures would avert about 1·5 million deaths a year, or 6-7% of all avertable deaths in low-income and middle-income countries. Second, essential surgical procedures rank among the most cost effective of all health interventions. The surgical platform of the first-level hospital delivers 28 of the 44 essential procedures, making investment in this platform also highly cost effective. Third, measures to expand access to surgery, such as task sharing, have been shown to be safe and effective while countries make long-term investments in building surgical and anaesthesia workforces. Because emergency procedures constitute 23 of the 28 procedures provided at first-level hospitals, expansion of access requires that such facilities be widely geographically diffused. Fourth, substantial disparities remain in the safety of surgical care, driven by high perioperative mortality rates including anaesthesia-related deaths in low-income and middle-income countries. Feasible measures, such as WHO's Surgical Safety Checklist, have led to improvements in safety and quality. Fifth, the large burden of surgical disorders, cost-effectiveness of essential surgery, and strong public demand for surgical services suggest that universal coverage of essential surgery should be financed early on the path to universal health coverage. We point to estimates that full coverage of the component of universal coverage of essential surgery applicable to first-level hospitals would require just over US$3 billion annually of additional spending and yield a benefit-cost ratio of more than 10:1. It would

  19. ic-cmtp3: 3rd International Conference on Competitive Materials and Technology Processes

    NASA Astrophysics Data System (ADS)

    2016-04-01

    Competitiveness is one of the most important factors in our lives and it plays a key role in the efficiency both of organizations and societies. The more scientifically advanced and prepared organizations develop more competitive materials with better physical, chemical, and biological properties, and the leading companies apply more competitive equipment and technological processes. The aims of the 3rd International Conference on Competitive Materials and Technology Processes (ic-cmtp3), and the 1st International Symposium on Innovative Carbons and Carbon Based Materials (is-icbm1) and the 1st International Symposium on Innovative Construction Materials (is-icm1) organized alongside are the following: —Promote new methods and results of scientific research in the fields of material, biological, environmental and technological sciences; —Exchange information between the theoretical and applied sciences as well as technical and technological implementations; —Promote communication and collaboration between the scientists, researchers and engineers of different nations, countries and continents. Among the major fields of interest are advanced and innovative materials with competitive characteristics, including mechanical, physical, chemical, biological, medical and thermal, properties and extreme dynamic strength. Their crystalline, nano - and micro-structures, phase transformations as well as details of their technological processes, tests and measurements are also in the focus of the ic-cmtp3 conference and the is-scbm1 and is-icm1 symposia. Multidisciplinary applications of material science and the technological problems encountered in sectors like ceramics, glasses, thin films, aerospace, automotive and marine industries, electronics, energy, construction materials, medicine, biosciences and environmental sciences are of particular interest. In accordance with the program of the ic-cmtp3 conference and is-icbm1 and is-icm1 symposia we have received more

  20. SESAME - A 3rd Generation Synchrotron Light Source for the Middle East

    SciTech Connect

    Ulkue, Dincer; Rahighi, Javad; Winick, Herman

    2007-01-19

    SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) will be the Middle East's first international research center. It is a cooperative venture by the scientists and governments of the region with founding members Bahrain, Egypt, Israel, Jordan, Pakistan, Palestine Authority, and Turkey. Iran is in the process of finalizing its formal membership. Other countries (Cyprus, Morocco, and the United Arab Emirates) are also expected to join. The permanent Council of member states has full responsibility for the project. Members provide the annual operating budget. Observer countries are Germany, Greece, Italy, Kuwait, Portugal, Russian Federation, Sweden, the UK, and the US. SESAME is being developed under the umbrella of UNESCO. Jordan was selected as the building site. SESAME will offer excellent opportunities for training of Middle East scientists and attract those working abroad to consider returning. SESAME will be a 2.5GeV 3rd Generation light source (emittance 26nm-rad, circumference {approx}133m), providing excellent performance for structural molecular biology, molecular environmental science, surface and interface science, microelectromechanical devices, x-ray imaging, archaeological microanalysis, and materials characterization. It will cover a broad spectral range from the infrared to hard x-rays and will have 12 straight sections for insertion devices (average length 2.75m). The injector will be the BESSY I 0.8 GeV booster synchrotron which has been given as a gift from Germany. Four committees advise the Council and assist in developing the technical design, beam lines, user community, and scientific Program. The SESAME building, now in construction with funds and a site provided by Jordan, is scheduled for completion in late 2006 after which the BESSY I injector will be installed. First stored beam in the new 2.5 GeV ring is planned for 2009 with six initial beamlines planned. Some beamlines will be built by member

  1. PREFACE: 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"

    NASA Astrophysics Data System (ADS)

    Yamada, Taiichi; Kanada-En'yo, Yoshiko

    2014-12-01

    The 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3) was held at KGU Kannai Media Center, Kanto Gakuin University, Yokohama, Japan, from May 26 to 30, 2014. Yokohama is the second largest city in Japan, about 25 km southeast of Tokyo. The first workshop of the series was held in Strasbourg, France, in 2008 and the second one was in Brussels, Belgium, in 2010. The purpose of SOTANCP3 was to discuss the present status and future perspectives of the nuclear cluster physics. The following nine topics were selected in order to cover most of the scientific programme and highlight an area where new ideas have emerged over recent years: (1) Cluster structures and many-body correlations in stable and unstable nuclei (2) Clustering aspects of nuclear reactions and resonances (3) Alpha condensates and analogy with condensed matter approaches (4) Role of tensor force in cluster physics and ab initio approaches (5) Clustering in hypernuclei (6) Nuclear fission, superheavy nuclei, and cluster decay (7) Cluster physics and nuclear astrophysics (8) Clustering in nuclear matter and neutron stars (9) Clustering in hadron and atomic physics There were 122 participants, including 53 from 17 foreign countries. In addition to invited talks, we had many talks selected from contributed papers. There were plenary, parallel, and poster sessions. Poster contributions were also presented as four-minute talks in parallel sessions. This proceedings contains the papers presented in invited and selected talks together with those presented in poster sessions. We would like to express our gratitude to the members of the International Advisory Committee and those of the Organizing Committee for their efforts which made this workshop successful. In particular we would like to present our great thanks to Drs. Y. Funaki, W. Horiuchi, N. Itagaki, M. Kimura, T. Myo, and T. Yoshida. We would like also to thank the following organizations for their sponsors: RCNP

  2. ProxiMAX randomization: a new technology for non-degenerate saturation mutagenesis of contiguous codons.

    PubMed

    Ashraf, Mohammed; Frigotto, Laura; Smith, Matthew E; Patel, Seema; Hughes, Marcus D; Poole, Andrew J; Hebaishi, Husam R M; Ullman, Christopher G; Hine, Anna V

    2013-10-01

    Back in 2003, we published 'MAX' randomization, a process of non-degenerate saturation mutagenesis using exactly 20 codons (one for each amino acid) or else any required subset of those 20 codons. 'MAX' randomization saturates codons located in isolated positions within a protein, as might be required in enzyme engineering, or else on one face of an α-helix, as in zinc-finger engineering. Since that time, we have been asked for an equivalent process that can saturate multiple contiguous codons in a non-degenerate manner. We have now developed 'ProxiMAX' randomization, which does just that: generating DNA cassettes for saturation mutagenesis without degeneracy or bias. Offering an alternative to trinucleotide phosphoramidite chemistry, ProxiMAX randomization uses nothing more sophisticated than unmodified oligonucleotides and standard molecular biology reagents. Thus it requires no specialized chemistry, reagents or equipment, and simply relies on a process of saturation cycling comprising ligation, amplification and digestion for each cycle. The process can encode both unbiased representation of selected amino acids or else encode them in predefined ratios. Each saturated position can be defined independently of the others. We demonstrate accurate saturation of up to 11 contiguous codons. As such, ProxiMAX randomization is particularly relevant to antibody engineering. PMID:24059507

  3. Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia

    NASA Astrophysics Data System (ADS)

    Bos, Johannes L.; Toksoz, Deniz; Marshall, Christopher J.; Verlaan-de Vries, Matty; Veeneman, Gerrit H.; van der Eb, Alex J.; van Boom, Jacques H.; Janssen, Johannes W. G.; Steenvoorden, Ada C. M.

    1985-06-01

    DNAs from four out of five patients with acute myeloid leukaemia (AML) tested by an in vivo selection assay in nude mice using transfected mouse NIH 3T3 cells were found to contain an activated N-ras oncogene. Using a set of synthetic oligonucleotide probes, we have detected a mutation at codon 13 in all four genes. The same codon is mutated in an additional AML DNA that is positive in the focus-formation assay on 3T3 cells. DNA from the peripheral blood of one patient in remission does not contain a codon 13 mutation.

  4. Comparative Analysis of Codon Usage Bias Patterns in Microsporidian Genomes

    PubMed Central

    Xiang, Heng; Zhang, Ruizhi; Butler, Robert R.; Liu, Tie; Zhang, Li; Pombert, Jean-François; Zhou, Zeyang

    2015-01-01

    The sub-3 Mbp genomes from microsporidian species of the Encephalitozoon genus are the smallest known among eukaryotes and paragons of genomic reduction and compaction in parasites. However, their diminutive stature is not characteristic of all Microsporidia, whose genome sizes vary by an order of magnitude. This large variability suggests that different evolutionary forces are applied on the group as a whole. In this study, we have compared the codon usage bias (CUB) between eight taxonomically distinct microsporidian genomes: Encephalitozoon intestinalis, Encephalitozoon cuniculi, Spraguea lophii, Trachipleistophora hominis, Enterocytozoon bieneusi, Nematocida parisii, Nosema bombycis and Nosema ceranae. While the CUB was found to be weak in all eight Microsporidia, nearly all (98%) of the optimal codons in S. lophii, T. hominis, E. bieneusi, N. parisii, N. bombycis and N. ceranae are fond of A/U in third position whereas most (64.6%) optimal codons in the Encephalitozoon species E. intestinalis and E. cuniculi are biased towards G/C. Although nucleotide composition biases are likely the main factor driving the CUB in Microsporidia according to correlation analyses, directed mutational pressure also likely affects the CUB as suggested by ENc-plots, correspondence and neutrality analyses. Overall, the Encephalitozoon genomes were found to be markedly different from the other microsporidians and, despite being the first sequenced representatives of this lineage, are uncharacteristic of the group as a whole. The disparities observed cannot be attributed solely to differences in host specificity and we hypothesize that other forces are at play in the lineage leading to Encephalitozoon species. PMID:26057384

  5. Comparative Analysis of Codon Usage Bias Patterns in Microsporidian Genomes.

    PubMed

    Xiang, Heng; Zhang, Ruizhi; Butler, Robert R; Liu, Tie; Zhang, Li; Pombert, Jean-François; Zhou, Zeyang

    2015-01-01

    The sub-3 Mbp genomes from microsporidian species of the Encephalitozoon genus are the smallest known among eukaryotes and paragons of genomic reduction and compaction in parasites. However, their diminutive stature is not characteristic of all Microsporidia, whose genome sizes vary by an order of magnitude. This large variability suggests that different evolutionary forces are applied on the group as a whole. In this study, we have compared the codon usage bias (CUB) between eight taxonomically distinct microsporidian genomes: Encephalitozoon intestinalis, Encephalitozoon cuniculi, Spraguea lophii, Trachipleistophora hominis, Enterocytozoon bieneusi, Nematocida parisii, Nosema bombycis and Nosema ceranae. While the CUB was found to be weak in all eight Microsporidia, nearly all (98%) of the optimal codons in S. lophii, T. hominis, E. bieneusi, N. parisii, N. bombycis and N. ceranae are fond of A/U in third position whereas most (64.6%) optimal codons in the Encephalitozoon species E. intestinalis and E. cuniculi are biased towards G/C. Although nucleotide composition biases are likely the main factor driving the CUB in Microsporidia according to correlation analyses, directed mutational pressure also likely affects the CUB as suggested by ENc-plots, correspondence and neutrality analyses. Overall, the Encephalitozoon genomes were found to be markedly different from the other microsporidians and, despite being the first sequenced representatives of this lineage, are uncharacteristic of the group as a whole. The disparities observed cannot be attributed solely to differences in host specificity and we hypothesize that other forces are at play in the lineage leading to Encephalitozoon species. PMID:26057384

  6. Positioning.

    ERIC Educational Resources Information Center

    Conone, Ruth M.

    The key to positioning is the creation of a clear benefit image in the consumer's mind. One positioning strategy is creating in the prospect's mind a position that takes into consideration the company's or agency's strengths and weaknesses as well as those of its competitors. Another strategy is to gain entry into a position ladder owned by…

  7. Stop Codon Reassignment in the Wild

    SciTech Connect

    Ivanova, Natalia; Schwientek, Patrick; Tripp, H. James; Rinke, Christian; Pati, Amrita; Huntemann, Marcel; Visel, Axel; Woyke, Tanja; Kyrpides, Nikos; Rubin, Edward

    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

  8. PREFACE: 3rd International Workshop on Materials Analysis and Processing in Magnetic Fields (MAP3)

    NASA Astrophysics Data System (ADS)

    Sakka, Yoshio; Hirota, Noriyuki; Horii, Shigeru; Ando, Tsutomu

    2009-07-01

    The 3rd International Workshop on Materials Analysis and Processing in Materials Fields (MAP3) was held on 14-16 May 2008 at the University of Tokyo, Japan. The first was held in March 2004 at the National High Magnetic Field Laboratory in Tallahassee, USA. Two years later the second took place in Grenoble, France. MAP3 was held at The University of Tokyo International Symposium, and jointly with MANA Workshop on Materials Processing by External Stimulation, and JSPS CORE Program of Construction of the World Center on Electromagnetic Processing of Materials. At the end of MAP3 it was decided that the next MAP4 will be held in Atlanta, USA in 2010. Processing in magnetic fields is a rapidly expanding research area with a wide range of promising applications in materials science. MAP3 focused on the magnetic field interactions involved in the study and processing of materials in all disciplines ranging from physics to chemistry and biology: Magnetic field effects on chemical, physical, and biological phenomena Magnetic field effects on electrochemical phenomena Magnetic field effects on thermodynamic phenomena Magnetic field effects on hydrodynamic phenomena Magnetic field effects on crystal growth Magnetic processing of materials Diamagnetic levitation Magneto-Archimedes effect Spin chemistry Application of magnetic fields to analytical chemistry Magnetic orientation Control of structure by magnetic fields Magnetic separation and purification Magnetic field-induced phase transitions Materials properties in high magnetic fields Development of NMR and MRI Medical application of magnetic fields Novel magnetic phenomena Physical property measurement by Magnetic fields High magnetic field generation> MAP3 consisted of 84 presentations including 16 invited talks. This volume of Journal of Physics: Conference Series contains the proceeding of MAP3 with 34 papers that provide a scientific record of the topics covered by the conference with the special topics (13 papers) in

  9. PREFACE: 3rd Workshop on Theory, Modelling and Computational Methods for Semiconductors (TMCSIII)

    NASA Astrophysics Data System (ADS)

    Califano, Marco; Migliorato, Max; Probert, Matt

    2012-05-01

    These conference proceedings contain the written papers of the contributions presented at the 3rd International Conference on Theory, Modelling and Computational Methods for Semiconductor materials and nanostructures. The conference was held at the School of Electronic and Electrical Engineering, University of Leeds, Leeds, UK on 18-20 January 2012. The previous conferences in this series took place in 2010 at St William's College, York and in 2008 at the University of Manchester, UK. The development of high-speed computer architectures is finally allowing the routine use of accurate methods for calculating the structural, thermodynamic, vibrational, optical and electronic properties of semiconductors and their hetero- and nano-structures. The scope of this conference embraces modelling, theory and the use of sophisticated computational tools in semiconductor science and technology, where there is substantial potential for time-saving in R&D. Theoretical approaches represented in this meeting included: Density Functional Theory, Tight Binding, Semiempirical Pseudopotential Methods, Effective Mass Models, Empirical Potential Methods and Multiscale Approaches. Topics included, but were not limited to: Optical and Transport Properties of Quantum Nanostructures including Colloids and Nanotubes, Plasmonics, Magnetic Semiconductors, Graphene, Lasers, Photonic Structures, Photovoltaic and Electronic Devices. This workshop ran for three days, with the objective of bringing together UK and international leading experts in the theoretical modelling of Group IV, III-V and II-VI semiconductors, as well as students, postdocs and early-career researchers. The first day focused on providing an introduction and overview of this vast field, aimed particularly at students, with several lectures given by recognised experts in various theoretical approaches. The following two days showcased some of the best theoretical research carried out in the UK in this field, with several

  10. FOREWORD: 3rd International Workshop on New Computational Methods for Inverse Problems (NCMIP 2013)

    NASA Astrophysics Data System (ADS)

    Blanc-Féraud, Laure; Joubert, Pierre-Yves

    2013-10-01

    Conference logo This volume of Journal of Physics: Conference Series is dedicated to the scientific contributions presented during the 3rd International Workshop on New Computational Methods for Inverse Problems, NCMIP 2013 (http://www.farman.ens-cachan.fr/NCMIP_2013.html). This workshop took place at Ecole Normale Supérieure de Cachan, in Cachan, France, on 22 May 2013, at the initiative of Institut Farman. The prior editions of NCMIP also took place in Cachan, France, firstly within the scope of the ValueTools Conference, in May 2011 (http://www.ncmip.org/2011/), and secondly at the initiative of Institut Farman, in May 2012 (http://www.farman.ens-cachan.fr/NCMIP_2012.html). The NCMIP Workshop focused on recent advances in the resolution of inverse problems. Indeed inverse problems appear in numerous scientific areas such as geophysics, biological and medical imaging, material and structure characterization, electrical, mechanical and civil engineering, and finances. The resolution of inverse problems consists of estimating the parameters of the observed system or structure from data collected by an instrumental sensing or imaging device. Its success firstly requires the collection of relevant observation data. It also requires accurate models describing the physical interactions between the instrumental device and the observed system, as well as the intrinsic properties of the solution itself. Finally, it requires the design of robust, accurate and efficient inversion algorithms. Advanced sensor arrays and imaging devices provide high rate and high volume data; in this context, the efficient resolution of the inverse problem requires the joint development of new models and inversion methods, taking computational and implementation aspects into account. During this one-day workshop, researchers had the opportunity to bring to light and share new techniques and results in the field of inverse problems. The topics of the workshop were: algorithms and computational

  11. Adaptive and Effortful Control and Academic Self-efficacy Beliefs on Achievement: A Longitudinal Study of 1st through 3rd Graders

    PubMed Central

    Liew, Jeffrey; McTigue, Erin; Barrois, Lisa; Hughes, Jan

    2009-01-01

    The linkages between self-regulatory processes and achievement were examined across three years in 733 children beginning at 1st grade (M = 6.57 years, SD = .39 at 1st grade) who were identified as lower achieving in literacy. Accounting for consistencies in measures (from one year prior) and for influences of child’s age, gender, IQ, ethnicity and economic adversity on achievement, results indicate that adaptive/effortful control at 1st grade contributed to both academic self-efficacy beliefs at 2nd grade, and reading (but not math) achievement at 3rd grade. Although academic self-efficacy did not partially mediate the linkage between adaptive/effortful control and achievement, academic self-efficacy beliefs were positively correlated with reading and math. Results support the notion that early efforts to promote children’s self-regulatory skills would enhance future academic self-beliefs and achievement, particularly in literacy. PMID:19169387

  12. Mechanical design and engineering of the 3.9 GHZ, 3rd harmonic SRF system at Fermilab

    SciTech Connect

    Don Mitchell et al.

    2004-08-05

    The mechanical development of the 3.9 GHz, 3rd Harmonic SRF System is summarized to include: the development of a full scale copper prototype cavity structure; the design of the niobium 3 cell and niobium 9 cell structures; the design of the helium vessel and cryostat; the HOM coupler design; and a preliminary look at the main coupler design. The manufacturing processes for forming, rolling, and e-beam welding the HOM coupler, cavity cells, and end tubes are also described. Due to the exotic materials and manufacturing processes used in this type of device, a cost estimate for the material and fabrication is provided. The 3rd harmonic design is organized via a web-based data management approach.

  13. Differential contribution of specific working memory components to mathematics achievement in 2nd and 3rd graders.

    PubMed

    Meyer, M L; Salimpoor, V N; Wu, S S; Geary, D C; Menon, V

    2010-04-01

    The contribution of the three core components of working memory (WM) to the development of mathematical skills in young children is poorly understood. The relation between specific WM components and Numerical Operations, which emphasize computation and fact retrieval, and Mathematical Reasoning, which emphasizes verbal problem solving abilities in 48 2nd and 50 3rd graders was assessed using standardized WM and mathematical achievement measures. For 2nd graders, the central executive and phonological components predicted Mathematical Reasoning skills; whereas the visuo-spatial component predicted both Mathematical Reasoning and Numerical Operations skills in 3rd graders. This pattern suggests that the central executive and phonological loop facilitate performance during early stages of mathematical learning whereas visuo-spatial representations play an increasingly important role during later stages. We propose that these changes reflect a shift from prefrontal to parietal cortical functions during mathematical skill acquisition. Implications for learning and individual differences are discussed. PMID:21660238

  14. Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

    PubMed

    Pibiri, Ivana; Lentini, Laura; Melfi, Raffaella; Gallucci, Giulia; Pace, Andrea; Spinello, Angelo; Barone, Giampaolo; Di Leonardo, Aldo

    2015-08-28

    Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importance of H-bonding and stacking π-π interactions. To improve the readthrough activity we changed the fluorine number and position in the PTC124 fluoroaryl moiety. The readthrough ability of these PTC124 derivatives was tested in human cells harboring reporter plasmids with premature stop codons in H2BGFP and FLuc genes as well as in cystic fibrosis (CF) IB3.1 cells with a nonsense mutation. Maintaining low toxicity, three of these molecules showed higher efficacy than PTC124 in the readthrough of the UGA premature stop codon and in recovering the expression of the CFTR protein in IB3.1 cells from cystic fibrosis patient. Molecular dynamics simulations performed with mutated CFTR mRNA fragments and active or inactive derivatives are in agreement with the suggested interaction of PTC124 with mRNA. PMID:26142488

  15. Saccharomyces cerevisiae ribosomes recognize non-AUG initiation codons.

    PubMed Central

    Zitomer, R S; Walthall, D A; Rymond, B C; Hollenberg, C P

    1984-01-01

    A series of Saccharomyces cerevisiae plasmids and mutant derivatives containing fusions of the Escherichia coli galactokinase gene, galK, to the yeast iso-1-cytochrome c CYC1 transcription unit were used to study the sequences affecting the initiation of translation in S. cerevisiae. When the CYC1 AUG initiation codon preceded the galK AUG codon and coding sequence and either the two AUGs were out of frame with each other or a nonsense codon was located between them, the expression of the galK gene was extremely low. Deletion of the CYC1 AUG and its surrounding sequences resulted in a 100-fold increase in galK expression. This dependence of galK expression on the elimination of the CYC1 AUG codon was used to select mutations in that codon. Then the ability of these altered initiation codons to serve in translational initiation was determined by reconstruction of the CYC1 gene 3' to and in frame with them. Initiation was found to occur at the codons UUG and AUA, but not at the codons AAA and AUC. Furthermore the codon UUG, when preceded by an A three nucleotides upstream, served as a better initiation codon than when a U was substituted for the A. The efficiency of translation from these non-AUG codons was quantitated by using a CYC1/galK protein-coding fusion and measuring cellular galactokinase levels. Initiation at the UUG codon was 6.9% as efficient as initiation at the wild-type AUG codon when preceded by an A three nucleotides upstream, but was over 10-fold less efficient when a U was substituted for that A. Initiation at AUA was 0.5% as efficient as at AUG. The effects of the sequences preceding the initiation codon are discussed in light of these results. PMID:6390186

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

    PubMed

    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. PMID:25901796

  17. The effect of surgical technique on lingual nerve damage during lower 3rd molar removal by dental students.

    PubMed

    Robinson, P P; Loescher, A R; Smith, K G

    1999-05-01

    We have previously shown that avoidance of lingual flap retraction with a Howarth periosteal elevator during lower 3rd molar removal, reduces the incidence of lingual nerve damage. In that study, the surgery was undertaken by qualified staff and we have now assessed the effect of revising the method taught to our junior undergraduate dental students. We evaluated the outcome of surgery undertaken by 2 consecutive years of students, each group being taught 1 of the 2 methods. A total of 200 patients requiring lower 3rd molar removal under local anaesthesia were included in the study. In year 1, the surgery included elevation of a lingual flap and insertion of a Howarth elevator adjacent to the lingual plate; in year 2 this part of the procedure was avoided by using a purely buccal approach. There were no significant differences between the levels of tooth eruption and types of impaction of the teeth removed in each year. Lingual sensory disturbance occurred in 3 patients in the 'flap' group (3.3%) and in 1 patient (0.9%) in the 'no flap' group. As this incidence is not significantly different in the 2 groups (P < 0.4), we conclude that avoidance of lingual retraction by students undertaking lower 3rd molar removal does not appear to place the lingual nerve at greater risk. In view of the results of our previous study, we therefore advocate this method for use in undergraduate dental education. PMID:10530161

  18. Codon-biased translation can be regulated by wobble-base tRNA modification systems during cellular stress responses

    PubMed Central

    Endres, Lauren; Dedon, Peter C; Begley, Thomas J

    2015-01-01

    tRNA (tRNA) is a key molecule used for protein synthesis, with multiple points of stress-induced regulation that can include transcription, transcript processing, localization and ribonucleoside base modification. Enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and has the potential to influence specific anticodon-codon interactions and regulate translation. Notably, altered tRNA modification has been linked to mitochondrial diseases and cancer progression. In this review, specific to Eukaryotic systems, we discuss how recent systems-level analyses using a bioanalytical platform have revealed that there is extensive reprogramming of tRNA modifications in response to cellular stress and during cell cycle progression. Combined with genome-wide codon bias analytics and gene expression studies, a model emerges in which stress-induced reprogramming of tRNA drives the translational regulation of critical response proteins whose transcripts display a distinct codon bias. Termed Modification Tunable Transcripts (MoTTs),1 we define them as (1) transcripts that use specific degenerate codons and codon biases to encode critical stress response proteins, and (2) transcripts whose translation is influenced by changes in wobble base tRNA modification. In this review we note that the MoTTs translational model is also applicable to the process of stop-codon recoding for selenocysteine incorporation, as stop-codon recoding involves a selective codon bias and modified tRNA to decode selenocysteine during the translation of a key subset of oxidative stress response proteins. Further, we discuss how in addition to RNA modification analytics, the comprehensive characterization of translational regulation of specific transcripts requires a variety of tools, including high coverage codon-reporters, ribosome profiling and linked genomic and proteomic approaches. Together these tools will yield important new insights into the role of translational

  19. Macroscale and Microscale Organic Experiments, 3rd Edition (by Kenneth L. Williamson)

    NASA Astrophysics Data System (ADS)

    Keeffe, Reviewed By James

    1999-11-01

    suggested semiempirical computations. Other new texts, for example that by Pavia et al. (3rd ed., 1999), take computation even further. New features in the third edition include reduction of the macroscale experimental quantities to amounts compatible with 14/20 standard-taper glassware. Additionally, there are some useful and characteristically clever equipment adaptations for microfiltration and gas phase IR spectra, a few new or updated experiments, replacement of all IR spectra by Fourier transform spectra, and routine use of 250-MHz 1H NMR spectra. Two-dimensional NMR spectroscopy is briefly discussed but not further encountered. One new feature which looks promising is called "Surfing the Web". Pertinent Web site addresses dot the book, but it would be useful if these were indexed as a group. The brief but up-to-date chapter on searching the literature includes addresses and some advice on accessing commercial databases. Regarding the lab course itself, two useful addresses are http://ull.chemistry.uakron.edu/organic_lab/ and Williamson's own site (under construction as I write), http://www.mtholyoke.edu/courses/kwilliam/microscale.shtml, where pictures of techniques and other support information will interest teachers and students alike. Williamson has always been responsive to users of his texts, and will probably be quick to incorporate new information and improved techniques at this site. There are a few areas where improvement can still be made. The chapter on IR spectroscopy, although revised, does not contain an extensive, conventional table of characteristic group frequencies. All our instructors supplement the text with standard tables. We also find the section on organic qualitative analysis to be limited and mildly difficult to use. Students must do a lot of page turning, back and forth, to find some of the tests and recipes needed. At SFSU more than half of our second-semester lab is given over to organic qual, and no single lab text except that of Pasto

  20. FOREWORD: 3rd International Workshop on New Computational Methods for Inverse Problems (NCMIP 2013)

    NASA Astrophysics Data System (ADS)

    Blanc-Féraud, Laure; Joubert, Pierre-Yves

    2013-10-01

    Conference logo This volume of Journal of Physics: Conference Series is dedicated to the scientific contributions presented during the 3rd International Workshop on New Computational Methods for Inverse Problems, NCMIP 2013 (http://www.farman.ens-cachan.fr/NCMIP_2013.html). This workshop took place at Ecole Normale Supérieure de Cachan, in Cachan, France, on 22 May 2013, at the initiative of Institut Farman. The prior editions of NCMIP also took place in Cachan, France, firstly within the scope of the ValueTools Conference, in May 2011 (http://www.ncmip.org/2011/), and secondly at the initiative of Institut Farman, in May 2012 (http://www.farman.ens-cachan.fr/NCMIP_2012.html). The NCMIP Workshop focused on recent advances in the resolution of inverse problems. Indeed inverse problems appear in numerous scientific areas such as geophysics, biological and medical imaging, material and structure characterization, electrical, mechanical and civil engineering, and finances. The resolution of inverse problems consists of estimating the parameters of the observed system or structure from data collected by an instrumental sensing or imaging device. Its success firstly requires the collection of relevant observation data. It also requires accurate models describing the physical interactions between the instrumental device and the observed system, as well as the intrinsic properties of the solution itself. Finally, it requires the design of robust, accurate and efficient inversion algorithms. Advanced sensor arrays and imaging devices provide high rate and high volume data; in this context, the efficient resolution of the inverse problem requires the joint development of new models and inversion methods, taking computational and implementation aspects into account. During this one-day workshop, researchers had the opportunity to bring to light and share new techniques and results in the field of inverse problems. The topics of the workshop were: algorithms and computational

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

    PubMed

    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. PMID:25445348

  2. Evaluating Sense Codon Reassignment with a Simple Fluorescence Screen.

    PubMed

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

    2015-12-22

    Understanding the interactions that drive the fidelity of the genetic code and the limits to which modifications can be made without breaking the translational system has practical implications for understanding the molecular mechanisms of evolution as well as expanding the set of encodable amino acids, particularly those with chemistries not provided by Nature. Because 61 sense codons encode 20 amino acids, reassigning the meaning of sense codons provides an avenue for biosynthetic modification of proteins, furthering both fundamental and applied biochemical research. We developed a simple screen that exploits the absolute requirement for fluorescence of an active site tyrosine in green fluorescent protein (GFP) to probe the pliability of the degeneracy of the genetic code. Our screen monitors the restoration of the fluorophore of GFP by incorporation of a tyrosine in response to a sense codon typically assigned another meaning in the genetic code. We evaluated sense codon reassignment at four of the 21 sense codons read through wobble interactions in Escherichia coli using the Methanocaldococcus jannaschii orthogonal tRNA/aminoacyl tRNA synthetase pair originally developed and commonly used for amber stop codon suppression. By changing only the anticodon of the orthogonal tRNA, we achieved sense codon reassignment efficiencies between 1% (Phe UUU) and 6% (Lys AAG). Each of the orthogonal tRNAs preferentially decoded the codon traditionally read via a wobble interaction in E. coli with the exception of the orthogonal tRNA with an AUG anticodon, which incorporated tyrosine in response to both the His CAU and His CAC codons with approximately equal frequencies. We applied our screen in a high-throughput manner to evaluate a 10(9)-member combined tRNA/aminoacyl tRNA synthetase library to identify improved sense codon reassigning variants for the Lys AAG codon. A single rapid screen with the ability to broadly evaluate reassignable codons will facilitate

  3. The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

    PubMed Central

    Sengupta, Supratim; Yang, Xiaoguang

    2007-01-01

    Many cases of nonstandard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The “gain” represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The “loss” represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is codon disappearance (CD), where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the unassigned codon mechanism, the loss occurs first, whereas in the ambiguous intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. CD is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense-to-sense reassignments cannot be explained by CD. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the unassigned codon and the ambiguous intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully. Electronic supplementary material The online version of this article (doi:10.1007/s00239-006-0284-7) contains supplementary material, which is available to authorized users. PMID:17541678

  4. Decoding system for the AUA codon by tRNAIle with the UAU anticodon in Mycoplasma mobile

    PubMed Central

    Taniguchi, Takaaki; Miyauchi, Kenjyo; Nakane, Daisuke; Miyata, Makoto; Muto, Akira; Nishimura, Susumu; Suzuki, Tsutomu

    2013-01-01

    Deciphering the genetic code is a fundamental process in all living organisms. In many bacteria, AUA codons are deciphered by tRNAIle2 bearing lysidine (L) at the wobble position. L is a modified cytidine introduced post-transcriptionally by tRNAIle-lysidine synthetase (TilS). Some bacteria, including Mycoplasma mobile, do not carry the tilS gene, indicating that they have established a different system to decode AUA codons. In this study, tRNAIle2 has been isolated from M. mobile and was found to contain a UAU anticodon without any modification. Mycoplasma mobile isoleucyl-tRNA synthetase (IleRS) recognized the UAU anticodon, whereas Escherichia coli IleRS did not efficiently aminoacylate tRNAIle2UAU. In M. mobile IleRS, a single Arg residue at position 865 was critical for specificity for the UAU anticodon and, when the corresponding site (W905) in E. coli IleRS was substituted with Arg, the W905R mutant efficiently aminoacylated tRNA with UAU anticodon. Mycoplasma mobile tRNAIle2 cannot distinguish between AUA and AUG codon on E. coli ribosome. However, on M. mobile ribosome, M. mobile tRNAIle2UAU specifically recognized AUA codon, and not AUG codon, suggesting M. mobile ribosome has a property that prevents misreading of AUG codon. These findings provide an insight into the evolutionary reorganization of the AUA decoding system. PMID:23295668

  5. Accuracy of initial codon selection by aminoacyl-tRNAs on the mRNA-programmed bacterial ribosome

    PubMed Central

    Zhang, Jingji; Ieong, Ka-Weng; Johansson, Magnus; Ehrenberg, Måns

    2015-01-01

    We used a cell-free system with pure Escherichia coli components to study initial codon selection of aminoacyl-tRNAs in ternary complex with elongation factor Tu and GTP on messenger RNA-programmed ribosomes. We took advantage of the universal rate-accuracy trade-off for all enzymatic selections to determine how the efficiency of initial codon readings decreased linearly toward zero as the accuracy of discrimination against near-cognate and wobble codon readings increased toward the maximal asymptote, the d value. We report data on the rate-accuracy variation for 7 cognate, 7 wobble, and 56 near-cognate codon readings comprising about 15% of the genetic code. Their d values varied about 400-fold in the 200–80,000 range depending on type of mismatch, mismatch position in the codon, and tRNA isoacceptor type. We identified error hot spots (d = 200) for U:G misreading in second and U:U or G:A misreading in third codon position by His-tRNAHis and, as also seen in vivo, Glu-tRNAGlu. We suggest that the proofreading mechanism has evolved to attenuate error hot spots in initial selection such as those found here. PMID:26195797

  6. Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species

    PubMed Central

    2006-01-01

    Background Codon usage has direct utility in molecular characterization of species and is also a marker for molecular evolution. To understand codon usage within the diverse phylum Nematoda, we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons were analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms. Results Codon usage similarity in Nematoda usually persists over the breadth of a genus but then rapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32% to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides (N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts. Conclusion Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes. PMID:26271136

  7. Codon Usage Domains over Bacterial Chromosomes

    PubMed Central

    Bailly-Bechet, Marc; Danchin, Antoine; Iqbal, Mudassar; Marsili, Matteo; Vergassola, Massimo

    2006-01-01

    The geography of codon bias distributions over prokaryotic genomes and its impact upon chromosomal organization are analyzed. To this aim, we introduce a clustering method based on information theory, specifically designed to cluster genes according to their codon usage and apply it to the coding sequences of Escherichia coli and Bacillus subtilis. One of the clusters identified in each of the organisms is found to be related to expression levels, as expected, but other groups feature an over-representation of genes belonging to different functional groups, namely horizontally transferred genes, motility, and intermediary metabolism. Furthermore, we show that genes with a similar bias tend to be close to each other on the chromosome and organized in coherent domains, more extended than operons, demonstrating a role of translation in structuring bacterial chromosomes. It is argued that a sizeable contribution to this effect comes from the dynamical compartimentalization induced by the recycling of tRNAs, leading to gene expression rates dependent on their genomic and expression context. PMID:16683018

  8. Kinetics of Stop Codon Recognition by Release Factor 1

    PubMed Central

    Hetrick, Byron; Lee, Kristin; Joseph, Simpson

    2009-01-01

    Recognition of stop codons by class I release factors is a fundamental step in the termination phase of protein synthesis. Since premature termination is costly to the cell, release factors have to efficiently discriminate between stop and sense codons. In order to understand the mechanism of discrimination between stop and sense codons, we developed a new, pre-steady state kinetic assay to monitor the interaction of RF1 with the ribosome. Our results show that RF1 associates with similar association rate constants to ribosomes programmed with a stop or sense codons. However, dissociation of RF1 from sense codons is as much as three orders of magnitude faster than from stop codons. Interestingly, the affinity of RF1 for ribosomes programmed with different sense codons does not correlate with the defects in peptide release. Thus, discrimination against sense codons is achieved, both, by increasing the dissociation rates and by decreasing the rate of peptide release. These results suggest that sense codons inhibit conformational changes necessary for RF1 to stably bind to the ribosome and catalyze peptide release. PMID:19874047

  9. Comparative context analysis of codon pairs on an ORFeome scale

    PubMed Central

    Moura, Gabriela; Pinheiro, Miguel; Silva, Raquel; Miranda, Isabel; Afreixo, Vera; Dias, Gaspar; Freitas, Adelaide; Oliveira, José L; Santos, Manuel AS

    2005-01-01

    Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context. PMID:15774029

  10. A computer program to display codon changes caused by mutagenesis.

    PubMed

    Sirotkin, K

    1988-04-01

    A FORTRAN program for displaying the correspondence between codon changes and different possible base changes is presented. Changes of both single bases and dimers are considered. The user can specify the mutagenesis spectrum. Additionally, the user can choose whether or not to consider single or double events in a codon and whether or not to consider the possibility that the change of two bases (a dimer) can overlap a codon boundary. Furthermore, a variety of ways may be chosen to display and summarize the codon changes that can result from the specified mutagenesis. A user-supplied sequence or the genetic code table can be analyzed. PMID:3167596

  11. Influence of solar eclipse of November 3rd, 2013 on the total ozone column over Badajoz, Spain

    NASA Astrophysics Data System (ADS)

    Mateos, D.; Antón, M.; Vaquero, J. M.

    2014-05-01

    The hybrid eclipse of November 3rd, 2013 was observed as partial with a magnitude equal to 0.126 from Badajoz (38° 53‧ N, 6° 58‧ W). The evolution of the total ozone column (TOC) values for 4 h was monitored using a Solar Light Microtops-II manual sun-photometer. Before the eclipse, TOC remained invariable ~280 Dobson Units (DU) for one hour and a half. Once the eclipse was started, a clear decrease in TOC occurred. After the eclipse maximum (with TOC=273 DU), a rapid TOC recovery was observed. When the eclipse was over, TOC came back to values ~280 DU.

  12. Quantitative metabolic profiles of 2nd and 3rd trimester human amniotic fluid using 1H HR-MAS spectroscopy

    PubMed Central

    Cohn, Brad R.; Zhao, Shoujun; Kornak, John; Zhang, Vickie Y.; Iman, Rahwa; Kurhanewicz, John; Vahidi, Kiarash; Yu, Jingwei; Caughey, Aaron B.; Swanson, Mark G.

    2016-01-01

    Object To establish and compare normative metabolite concentrations in 2nd and 3rd trimester human amniotic fluid samples in an effort to reveal metabolic biomarkers of fetal health and development. Materials and methods Twenty-one metabolite concentrations were compared between 2nd (15–27 weeks gestation, N = 23) and 3rd (29–39 weeks gestation, N = 27) trimester amniotic fluid samples using 1H high resolution magic angle spinning (HR-MAS) spectroscopy. Data were acquired using the electronic reference to access in vivo concentrations method and quantified using a modified semi-parametric quantum estimation algorithm modified for high-resolution ex vivo data. Results Sixteen of 21 metabolite concentrations differed significantly between 2nd and 3rd trimester groups. Betaine (0.00846±0.00206 mmol/kg vs. 0.0133±0.0058 mmol/kg, P <0.002) and creatinine (0.0124±0.0058 mmol/kg vs. 0.247±0.011 mmol/kg, P <0.001) concentrations increased significantly, while glucose (5.96±1.66 mmol/kg vs. 2.41±1.69 mmol/kg, P <0.001), citrate (0.740±0.217 mmol/kg vs. 0.399±0.137 mmol/kg, P <0.001), pyruvate (0.0659±0.0103 mmol/kg vs. 0.0299±0.286 mmol/kg, P <0.001), and numerous amino acid (e.g. alanine, glutamate, isoleucine, leucine, lysine, and valine) concentrations decreased significantly with advancing gestation. A stepwise multiple linear regression model applied to 50 samples showed that gestational age can be accurately predicted using combinations of alanine, glucose and creatinine concentrations. Conclusion These results provide key normative data for 2nd and 3rd trimester amniotic fluid metabolite concentrations and provide the foundation for future development of magnetic resonance spectroscopy (MRS) biomarkers to evaluate fetal health and development. PMID:19779747

  13. A novel mutation in Prph2, a gene regulated by Nr2e3, causes retinal degeneration and outer segment defects similar to Nr2e3rd7/rd7 retinas

    PubMed Central

    Nystuen, Arne M.; Sachs, Andrew J.; Yuan, Yang; Heuermann, Laura; Haider, Neena B.

    2014-01-01

    The nmf193 mutant was generated by a large-scale ENU mutagenesis screen and originally described as having a dominantly inherited phenotype characterized by fundus abnormalities. We determined that nmf193 mice exhibit outer segment defects and progressive retinal degeneration. Clinical examination revealed retinal spotting apparent at 6 weeks of age. Histological analysis of homozygous mutant mice at 6 weeks indicated an absence of outer segments (OS) and a 50% reduction of photoreceptor cells which progressed to complete loss of photoreceptors by 10 months. Mice heterozygous for the nmf193 mutation had a less severe phenotype of shortened outer segments at 2 months with progressive loss of photoreceptor cells to 50% by 10 months. A positional cloning approach using a DNA pooling strategy was performed to identify the causative mutation in nmf193 mice. The nmf193 mutation linked to chromosome 17 and fine mapped to an interval containing the peripherin/rds (Prph2) gene. Mutation analysis identified a single base change in Prph2 that causes aberrant splicing between exon 1 and 2. Interestingly, a comparative histological analysis demonstrated that Prph2nmf193/+ mutants have similar photoreceptor degeneration to that of Nr2e3rd7/rd7. We show that Prph2 mRNA and protein levels are reduced in the Nr2e3rd7/rd7 mutant compared to control littermates. Further, chromatin immunoprecipitation analysis shows that Prph2 is a direct target of NR2E3. In addition, the down-regulation of Prph2 gene expression is similar in both the Nr2e3rd7/rd7 and Prph2nmf193/+ mutants suggesting that the reduction of Prph2 may contribute to the degenerative pathology seen in Nr2e3rd7/rd7. PMID:18763016

  14. The surprising negative correlation of gene length and optimal codon use - disentangling translational selection from GC-biased gene conversion in yeast

    PubMed Central

    2011-01-01

    Background Surprisingly, in several multi-cellular eukaryotes optimal codon use correlates negatively with gene length. This contrasts with the expectation under selection for translational accuracy. While suggested explanations focus on variation in strength and efficiency of translational selection, it has rarely been noticed that the negative correlation is reported only in organisms whose optimal codons are biased towards codons that end with G or C (-GC). This raises the question whether forces that affect base composition - such as GC-biased gene conversion - contribute to the negative correlation between optimal codon use and gene length. Results Yeast is a good organism to study this as equal numbers of optimal codons end in -GC and -AT and one may hence compare frequencies of optimal GC- with optimal AT-ending codons to disentangle the forces. Results of this study demonstrate in yeast frequencies of GC-ending (optimal AND non-optimal) codons decrease with gene length and increase with recombination. A decrease of GC-ending codons along genes contributes to the negative correlation with gene length. Correlations with recombination and gene expression differentiate between GC-ending and optimal codons, and also substitution patterns support effects of GC-biased gene conversion. Conclusion While the general effect of GC-biased gene conversion is well known, the negative correlation of optimal codon use with gene length has not been considered in this context before. Initiation of gene conversion events in promoter regions and the presence of a gene conversion gradient most likely explain the observed decrease of GC-ending codons with gene length and gene position. PMID:21481245

  15. Evaluation of codon biology in citrus and Poncirus trifoliata based on genomic features and frame corrected expressed sequence tags.

    PubMed

    Ahmad, Touqeer; Sablok, Gaurav; Tatarinova, Tatiana V; Xu, Qiang; Deng, Xiu-Xin; Guo, Wen-Wu

    2013-04-01

    Citrus, as one of the globally important fruit trees, has been an object of interest for understanding genetics and evolutionary process in fruit crops. Meta-analyses of 19 Citrus species, including 4 globally and economically important Citrus sinensis, Citrus clementina, Citrus reticulata, and 1 Citrus relative Poncirus trifoliata, were performed. We observed that codons ending with A- or T- at the wobble position were preferred in contrast to C- or G- ending codons, indicating a close association with AT richness of Citrus species and P. trifoliata. The present study postulates a large repertoire of a set of optimal codons for the Citrus genus and P. trifoliata and demonstrates that GCT and GGT are evolutionary conserved optimal codons. Our observation suggested that mutational bias is the dominating force in shaping the codon usage bias (CUB) in Citrus and P. trifoliata. Correspondence analysis (COA) revealed that the principal axis [axis 1; COA/relative synonymous codon usage (RSCU)] contributes only a minor portion (∼10.96%) of the recorded variance. In all analysed species, except P. trifoliata, Gravy and aromaticity played minor roles in resolving CUB. Compositional constraints were found to be strongly associated with the amino acid signatures in Citrus species and P. trifoliata. Our present analysis postulates compositional constraints in Citrus species and P. trifoliata and plausible role of the stress with GC3 and coevolution pattern of amino acid. PMID:23315666

  16. Evaluation of Codon Biology in Citrus and Poncirus trifoliata Based on Genomic Features and Frame Corrected Expressed Sequence Tags

    PubMed Central

    Ahmad, Touqeer; Sablok, Gaurav; Tatarinova, Tatiana V.; Xu, Qiang; Deng, Xiu-Xin; Guo, Wen-Wu

    2013-01-01

    Citrus, as one of the globally important fruit trees, has been an object of interest for understanding genetics and evolutionary process in fruit crops. Meta-analyses of 19 Citrus species, including 4 globally and economically important Citrus sinensis, Citrus clementina, Citrus reticulata, and 1 Citrus relative Poncirus trifoliata, were performed. We observed that codons ending with A- or T- at the wobble position were preferred in contrast to C- or G- ending codons, indicating a close association with AT richness of Citrus species and P. trifoliata. The present study postulates a large repertoire of a set of optimal codons for the Citrus genus and P. trifoliata and demonstrates that GCT and GGT are evolutionary conserved optimal codons. Our observation suggested that mutational bias is the dominating force in shaping the codon usage bias (CUB) in Citrus and P. trifoliata. Correspondence analysis (COA) revealed that the principal axis [axis 1; COA/relative synonymous codon usage (RSCU)] contributes only a minor portion (∼10.96%) of the recorded variance. In all analysed species, except P. trifoliata, Gravy and aromaticity played minor roles in resolving CUB. Compositional constraints were found to be strongly associated with the amino acid signatures in Citrus species and P. trifoliata. Our present analysis postulates compositional constraints in Citrus species and P. trifoliata and plausible role of the stress with GC3 and coevolution pattern of amino acid. PMID:23315666

  17. A facile and efficient transposon mutagenesis method for generation of multi-codon deletions in protein sequences.

    PubMed

    Liu, Shu-Su; Wei, Xuan; Ji, Qun; Xin, Xiu; Jiang, Biao; Liu, Jia

    2016-06-10

    Substitutions, insertions and deletions are all important mutation events in natural and laboratory protein evolution. However, protein engineering using insertions and deletions (indels) is hindered by the lack of a convenient mutagenesis method. Here, we describe a general transposon mutagenesis method that allows for removal of up to five consecutive in-frame codons from a random position of a target protein. This method, referred to as codon deletion mutagenesis (CDM), relies on an engineered Mu transposon that carries asymmetric terminal sequences flanking the MuA transposase recognition sites. CDM requires minimal DNA manipulations, and can generate multi-codon deletions with high efficiency (>90%). As a proof of principle, we constructed five libraries of green fluorescent protein (GFP) containing one to five random codon deletions, respectively. Several variants with multi-codon deletions remained fluorescent, none of which could be easily identified using traditional mutagenesis method. CDM provides a facile and efficient approach to sampling a protein sequence with multi-codon deletions. It will not only facilitate our understanding of the effects of amino acid deletions on protein function but also expedite protein engineering using deletion mutagenesis. PMID:27071724

  18. Most Used Codons per Amino Acid and per Genome in the Code of Man Compared to Other Organisms According to the Rotating Circular Genetic Code

    PubMed Central

    Castro-Chavez, Fernando

    2011-01-01

    My previous theoretical research shows that the rotating circular genetic code is a viable tool to make easier to distinguish the rules of variation applied to the amino acid exchange; it presents a precise and positional bio-mathematical balance of codons, according to the amino acids they codify. Here, I demonstrate that when using the conventional or classic circular genetic code, a clearer pattern for the human codon usage per amino acid and per genome emerges. The most used human codons per amino acid were the ones ending with the three hydrogen bond nucleotides: C for 12 amino acids and G for the remaining 8, plus one codon for arginine ending in A that was used approximately with the same frequency than the one ending in G for this same amino acid (plus *). The most used codons in man fall almost all the time at the rightmost position, clockwise, ending either in C or in G within the circular genetic code. The human codon usage per genome is compared to other organisms such as fruit flies (Drosophila melanogaster), squid (Loligo pealei), and many others. The biosemiotic codon usage of each genomic population or ‘Theme’ is equated to a ‘molecular language’. The C/U choice or difference, and the G/A difference in the third nucleotide of the most used codons per amino acid are illustrated by comparing the most used codons per genome in humans and squids. The human distribution in the third position of most used codons is a 12-8-2, C-G-A, nucleotide ending signature, while the squid distribution in the third position of most used codons was an odd, or uneven, distribution in the third position of its most used codons: 13-6-3, U-A-G, as its nucleotide ending signature. These findings may help to design computational tools to compare human genomes, to determine the exchangeability between compatible codons and amino acids, and for the early detection of incompatible changes leading to hereditary diseases. PMID:22997484

  19. Stop codons in bacteria are not selectively equivalent

    PubMed Central

    2012-01-01

    Background The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes. Results We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG. Conclusions Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications. Reviewers This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section. PMID:22974057

  20. Analysis and design of a 3rd order velocity-controlled closed-loop for MEMS vibratory gyroscopes.

    PubMed

    Wu, Huan-ming; Yang, Hai-gang; Yin, Tao; Jiao, Ji-wei

    2013-01-01

    The time-average method currently available is limited to analyzing the specific performance of the automatic gain control-proportional and integral (AGC-PI) based velocity-controlled closed-loop in a micro-electro-mechanical systems (MEMS) vibratory gyroscope, since it is hard to solve nonlinear functions in the time domain when the control loop reaches to 3rd order. In this paper, we propose a linearization design approach to overcome this limitation by establishing a 3rd order linear model of the control loop and transferring the analysis to the frequency domain. Order reduction is applied on the built linear model's transfer function by constructing a zero-pole doublet, and therefore mathematical expression of each control loop's performance specification is obtained. Then an optimization methodology is summarized, which reveals that a robust, stable and swift control loop can be achieved by carefully selecting the system parameters following a priority order. Closed-loop drive circuits are designed and implemented using 0.35 μm complementary metal oxide semiconductor (CMOS) process, and experiments carried out on a gyroscope prototype verify the optimization methodology that an optimized stability of the control loop can be achieved by constructing the zero-pole doublet, and disturbance rejection capability (D.R.C) of the control loop can be improved by increasing the integral term. PMID:24051522

  1. Poly(2-oxazoline) based micelles with high capacity for 3rd generation taxoids: preparation, in vitro and in vivo evaluation.

    PubMed

    He, Zhijian; Schulz, Anita; Wan, Xiaomeng; Seitz, Joshua; Bludau, Herdis; Alakhova, Daria Y; Darr, David B; Perou, Charles M; Jordan, Rainer; Ojima, Iwao; Kabanov, Alexander V; Luxenhofer, Robert

    2015-06-28

    The clinically and commercially successful taxanes, paclitaxel and docetaxel suffer from two major drawbacks, namely their very low aqueous solubility and the risk of developing resistance. Here, we present a method that overcomes both drawbacks in a very simple manner. We formulated 3rd generation taxoids, able to avoid common drug resistance mechanisms with doubly amphiphilic poly(2-oxazoline)s (POx), a safe and highly efficient polymer for the formulation of extremely hydrophobic drugs. We found excellent solubilization of different 3rd generation taxoids irrespective of the drug's chemical structures with essentially quantitative drug loading and final drug to polymer ratios around unity. The small, highly loaded micelles with a hydrodynamic diameter of less than 100nm are excellently suited for parenteral administration. Moreover, a selected formulation with the taxoid SB-T-1214 is about one to two orders of magnitude more active in vitro than paclitaxel in the multidrug resistant breast cancer cell line LCC6-MDR. In contrast, in wild-type LCC6, no difference was observed. Using a q4d×4 dosing regimen, we also found that POx/SB-T-1214 significantly inhibits the growth of LCC6-MDR orthotropic tumors, outperforming commercial paclitaxel drug Taxol and Cremophor EL formulated SB-T-1214. PMID:25725361

  2. Analysis and Design of a 3rd Order Velocity-Controlled Closed-Loop for MEMS Vibratory Gyroscopes

    PubMed Central

    Wu, Huan-ming; Yang, Hai-gang; Yin, Tao; Jiao, Ji-wei

    2013-01-01

    The time-average method currently available is limited to analyzing the specific performance of the automatic gain control-proportional and integral (AGC-PI) based velocity-controlled closed-loop in a micro-electro-mechanical systems (MEMS) vibratory gyroscope, since it is hard to solve nonlinear functions in the time domain when the control loop reaches to 3rd order. In this paper, we propose a linearization design approach to overcome this limitation by establishing a 3rd order linear model of the control loop and transferring the analysis to the frequency domain. Order reduction is applied on the built linear model's transfer function by constructing a zero-pole doublet, and therefore mathematical expression of each control loop's performance specification is obtained. Then an optimization methodology is summarized, which reveals that a robust, stable and swift control loop can be achieved by carefully selecting the system parameters following a priority order. Closed-loop drive circuits are designed and implemented using 0.35 μm complementary metal oxide semiconductor (CMOS) process, and experiments carried out on a gyroscope prototype verify the optimization methodology that an optimized stability of the control loop can be achieved by constructing the zero-pole doublet, and disturbance rejection capability (D.R.C) of the control loop can be improved by increasing the integral term. PMID:24051522

  3. Does stereo-endoscopy improve neurosurgical targeting in 3rd ventriculostomy?

    NASA Astrophysics Data System (ADS)

    Abhari, Kamyar; de Ribaupierre, Sandrine; Peters, Terry; Eagleson, Roy

    2011-03-01

    Endoscopic third ventriculostomy is a minimally invasive surgical technique to treat hydrocephalus; a condition where patients suffer from excessive amounts of cerebrospinal fluid (CSF) in the ventricular system of their brain. This technique involves using a monocular endoscope to locate the third ventricle, where a hole can be made to drain excessive fluid. Since a monocular endoscope provides only a 2D view, it is difficult to make this perforation due to the lack of monocular cues and depth perception. In a previous study, we had investigated the use of a stereo-endoscope to allow neurosurgeons to locate and avoid hazardous areas on the surface of the third ventricle. In this paper, we extend our previous study by developing a new methodology to evaluate the targeting performance in piercing the hole in the membrane. We consider the accuracy of this surgical task and derive an index of performance for a task which does not have a well-defined position or width of target. Our performance metric is sensitive and can distinguish between experts and novices. We make use of this metric to demonstrate an objective learning curve on this task for each subject.

  4. Nonsense codons trigger an RNA partitioning shift.

    PubMed

    Bhalla, Angela D; Gudikote, Jayanthi P; Wang, Jun; Chan, Wai-Kin; Chang, Yao-Fu; Olivas, O Renee; Wilkinson, Miles F

    2009-02-13

    T-cell receptor-beta (TCRbeta) genes naturally acquire premature termination codons (PTCs) as a result of programmed gene rearrangements. PTC-bearing TCRbeta transcripts are dramatically down-regulated to protect T-cells from the deleterious effects of the truncated proteins that would otherwise be produced. Here we provide evidence that two responses collaborate to elicit this dramatic down-regulation. One is rapid mRNA decay triggered by the nonsense-mediated decay (NMD) RNA surveillance pathway. We demonstrate that this occurs in highly purified nuclei lacking detectable levels of three different cytoplasmic markers, but containing an outer nuclear membrane marker, suggesting that decay occurs either in the nucleoplasm or at the outer nuclear membrane. The second response is a dramatic partitioning shift in the nuclear fraction-to-cytoplasmic fraction mRNA ratio that results in few TCRbeta transcripts escaping to the cytoplasmic fraction of cells. Analysis of TCRbeta mRNA kinetics after either transcriptional repression or induction suggested that this nonsense codon-induced partitioning shift (NIPS) response is not the result of cytoplasmic NMD but instead reflects retention of PTC(+) TCRbeta mRNA in the nuclear fraction of cells. We identified TCRbeta sequences crucial for NIPS but found that NIPS is not exclusively a property of TCRbeta transcripts, and we identified non-TCRbeta sequences that elicit NIPS. RNA interference experiments indicated that NIPS depends on the NMD factors UPF1 and eIF4AIII but not the NMD factor UPF3B. We propose that NIPS collaborates with NMD to retain and degrade a subset of PTC(+) transcripts at the outer nuclear membrane and/or within the nucleoplasm. PMID:19091751

  5. Innovative Strategies for Enhancing Geoscience: Lesson Plans from the 3rd Millennium B.C.E.

    NASA Astrophysics Data System (ADS)

    Romani, P. N.; Bartholomew, I.; Frank, M.; Hackett, K.; Jackson, T.; Melzer, S.; 6th Grade,

    2002-05-01

    Each year the fifth and sixth grade students at Glenarden Woods Elementary Magnet School for Talented and Gifted (TAG) Students, in Glenarden, Maryland study an ancient culture to provide a unifying theme to their studies. The thematic unit is year-long and involves language arts, social studies, and art. Originally, the curriculum did not include any math or science, but for the past seven years we have been working to integrate the technology of the ancient culture into the program. Our goals are to keep the science as hands on as possible and to have the students learn by solving problems. This year's culture was ancient Egypt and the math and science components had a distinctive geoscience flavor to them. The initial problem for the students was to how to lay out a pyramid so that the four sides were aligned with the four cardinal directions as the pyramids are in Egypt. In keeping with the spirit of their studies they had to do so as the Egyptians did, i.e. without a pole star and without the use of any "modern" conveniences such as compasses, global positioning systems, etc. The problem was solved by measurements and observations of a gnomon's shadow. This work then provided a nice springboard for their next problem, duplicating Eratosthenes's measurement of the circumference of the Earth. Eratosthenes was a Greek who lived and experimented in Egypt in the Ptolemaic era. His determination of the Earth's circumference was within 15% of the modern day value. For this work the students had to team with other elementary students in Amherst, Massachusetts. We will present how we did the projects and lessons learned.

  6. [Codon usage bias in the straw mushroom Volvariella volvacea].

    PubMed

    Jiang, Wei; Lü, Beibei; He, Jianhua; Wang, Jinbin; Wu, Xiao; Wu, Guogan; Bao, Dapeng; Chen, Mingjie; Zhang, Jinsong; Tan, Qi; Tang, Xueming

    2014-09-01

    We analyzed the whole genome coding sequence of Volvariella volvacea to study the pattern utilization of codons by Codon W 1.4.2. As results, 24 optimal codons were identified. Moreover, the frequency of codons usage was calculated by CUSP program. We compared the frequency of codons usage of V. volvacea with other organisms including 6 modal value species (Homo sapiens, Saccharomys cerevisiae, Arabidopsis thalian, Mus musculus, Danio rerio and Drosophila melanogaster) and 4 edible fungi (Coprinopsis cinerea, Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus). We found that there were less differences in 3 edible fungi (excluding Pleurotus ostreatus) than 6 modal value species, comparing with the frequency of codons usage of V. volvacea. With software SPSS16.0, cluster analysis which showed differences in the size of codon bias, reflects the evolutionary relationships between species, which can be used as a reference of evolutionary relationships of species. This was the first time for analysis the codon preference among the whole coding sequences of edible fungi, serving as theoretical basis to apply genetic engineering of V. volvacea. PMID:25720157

  7. Synonymous codon usage pattern in glycoprotein gene of rabies virus.

    PubMed

    Morla, Sudhir; Makhija, Aditi; Kumar, Sachin

    2016-06-10

    Rabies virus (RABV) is the causative agent of a fatal nervous system ailment. The disease is zoonotic and prevalent in many developing countries. The glycoprotein (G) of RABV is the major antigenic determinant of the virus and plays a pivotal role in its neurovirulence. Various aspects of 'G' protein biology have been explored, but the factors affecting the nucleotide choice and synonymous codon usage have never been reported. In the present study, we have analyzed the relative synonymous codon usage and effective number of codons (Nc) using 132 'G' protein genes of RABV. Corresponding analysis was used to calculate major trends in codon usage. The correlation between base composition and codon usage as well as the plot between Nc and GC3 suggest that mutational pressure is the major factor that influences the codon usage in the G gene of RABV. In addition, factors like aromaticity, aliphatic index and hydropathy have shown slight correlation suggesting that natural selection also contributes to the codon usage variations of the 'G' gene. In conclusion, codon usage bias in 'G' gene of RABV is mainly by mutational pressure and natural selection. PMID:26945626

  8. A model of protein translation including codon bias, nonsense errors, and ribosome recycling.

    PubMed

    Gilchrist, Michael A; Wagner, Andreas

    2006-04-21

    We present and analyse a model of protein translation at the scale of an individual messenger RNA (mRNA) transcript. The model we develop is unique in that it incorporates the phenomena of ribosome recycling and nonsense errors. The model conceptualizes translation as a probabilistic wave of ribosome occupancy traveling down a heterogeneous medium, the mRNA transcript. Our results show that the heterogeneity of the codon translation rates along the mRNA results in short-scale spikes and dips in the wave. Nonsense errors attenuate this wave on a longer scale while ribosome recycling reinforces it. We find that the combination of nonsense errors and codon usage bias can have a large effect on the probability that a ribosome will completely translate a transcript. We also elucidate how these forces interact with ribosome recycling to determine the overall translation rate of an mRNA transcript. We derive a simple cost function for nonsense errors using our model and apply this function to the yeast (Saccharomyces cervisiae) genome. Using this function we are able to detect position dependent selection on codon bias which correlates with gene expression levels as predicted a priori. These results indirectly validate our underlying model assumptions and confirm that nonsense errors can play an important role in shaping codon usage bias. PMID:16171830

  9. Use of 2nd and 3rd Level Correlation Analysis for Studying Degradation in Polycrystalline Thin-Film Solar Cells

    SciTech Connect

    Albin, D. S.; del Cueto, J. A.; Demtsu, S. H.; Bansal, S.

    2011-03-01

    The correlation of stress-induced changes in the performance of laboratory-made CdTe solar cells with various 2nd and 3rd level metrics is discussed. The overall behavior of aggregated data showing how cell efficiency changes as a function of open-circuit voltage (Voc), short-circuit current density (Jsc), and fill factor (FF) is explained using a two-diode, PSpice model in which degradation is simulated by systematically changing model parameters. FF shows the highest correlation with performance during stress, and is subsequently shown to be most affected by shunt resistance, recombination and in some cases voltage-dependent collection. Large decreases in Jsc as well as increasing rates of Voc degradation are related to voltage-dependent collection effects and catastrophic shunting respectively. Large decreases in Voc in the absence of catastrophic shunting are attributed to increased recombination. The relevance of capacitance-derived data correlated with both Voc and FF is discussed.

  10. THE 3rd SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETY CONFERENCE, 14-18 APRIL 2012, FLORENCE, ITALY: SUMMARIES OF ORAL SESSIONS

    PubMed Central

    Abbs, Brandon; Achalia, Rashmin M; Adelufosi, Adegoke O; Aktener, Ahmet Yiğit; Beveridge, Natalie J; Bhakta, Savita G; Blackman, Rachael K; Bora, Emre; Byun, MS; Cabanis, Maurice; Carrion, Ricardo; Castellani, Christina A; Chow, Tze Jen; Dmitrzak-Weglarz, M; Gayer-Anderson, Charlotte; Gomes, Felipe V; Haut, Kristen; Hori, Hiroaki; Kantrowitz, Joshua T; Kishimoto, Taishiro; Lee, Frankie HF; Lin, Ashleigh; Palaniyappan, Lena; Quan, Meina; Rubio, Maria D; Ruiz de Azúa, Sonia; Sahoo, Saddichha; Strauss, Gregory P; Szczepankiewicz, Aleksandra; Thompson, Andrew D; Trotta, Antonella; Tully, Laura M; Uchida, Hiroyuki; Velthorst, Eva; Young, Jared W; O’Shea, Anne; DeLisi, Lynn E.

    2013-01-01

    The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012.and this year had as its emphasis, “The Globalization of Research”. Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. PMID:22910407

  11. Sunphotometric Measurement of Columnar H2O and Aerosol Optical Depth During the 3rd Water Vapor IOP in Fall 2000 at the SGP ARM Site

    NASA Technical Reports Server (NTRS)

    Schmid, B; Eilers, J. A.; McIntosh, D. M.; Longo, K.; Livingston, J. M.; Redemann, J.; Russell, P. B.; Braun, J.; Rocken, C.; Hipskind, R. Stephen (Technical Monitor)

    2001-01-01

    We conducted ground-based measurements with the Ames Airborne Tracking 6-channel Sunphotometer (AATS-6) during the 3rd Water Vapor IOP (WVIOP3), September 18 - October 8, 2000 at the SGP ARM site. For this deployment our primary result was columnar water vapor (CWV) obtained from continuous solar transmittance measurements in the 0.94-micron band. In addition, we simultaneously measured aerosol optical depth (AOD) at 380, 450, 525, 864 and 1020 nm. During the IOP, preliminary results of CWV and AOD were displayed in real-time. The result files were made available to other investigators by noon of the next day. During WVIOP3 those data were shown on the daily intercomparison plots on the IOP web-site. Our preliminary results for CWV fell within the spread of values obtained from other techniques. After conclusion of WVIOP3, AATS-6 was shipped directly to Mauna Loa, Hawaii for post-mission calibration. The updated calibration, a cloud screening technique for AOD, along with other mostly cosmetic changes were applied to the WVIOP3 data set and released as version 0.1. The resulting changes in CWV are small, the changes in AOD and Angstrom parameter are more noticeable. Data version 0.1 was successfully submitted to the ARM External Data Center. In the poster we will show data examples for both CWV and AOD. We will also compare our CWV results with those obtained from a GPS (Global Positioning System) slant path method.

  12. Structural Basis for Translation Termination on a Pseudouridylated Stop Codon.

    PubMed

    Svidritskiy, Egor; Madireddy, Rohini; Korostelev, Andrei A

    2016-05-22

    Pseudouridylation of messenger RNA emerges as an abundant modification involved in gene expression regulation. Pseudouridylation of stop codons in eukaryotic and bacterial cells results in stop-codon read through. The structural mechanism of this phenomenon is not known. Here we present a 3.1-Å crystal structure of Escherichia coli release factor 1 (RF1) bound to the 70S ribosome in response to the ΨAA codon. The structure reveals that recognition of a modified stop codon does not differ from that of a canonical stop codon. Our in vitro biochemical results support this finding by yielding nearly identical rates for peptide release from E. coli ribosomes programmed with pseudouridylated and canonical stop codons. The crystal structure also brings insight into E. coli RF1-specific interactions and suggests involvement of L27 in bacterial translation termination. Our results are consistent with a mechanism in which read through of a pseudouridylated stop codon in bacteria results from increased decoding by near-cognate tRNAs (miscoding) rather than from decreased efficiency of termination. PMID:27107638

  13. Premature termination codons in modern human genomes

    PubMed Central

    Fujikura, Kohei

    2016-01-01

    The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which indicate a human knockout. From a total of 7595 participants from two population exome projects, 246 PTCs were found where natural selection has resulted in new alleles with a high frequency (from 1% to 96%) of derived alleles and various levels of population differentiation (FST = 0.00139–0.626). The PTC genes formed protein and regulatory networks limited to 15 biological processes or gene families, of which seven categories were previously unreported. PTC mutations have a strong tendency to be introduced into members of the same gene family, even during modern human evolution, although the exact nature of the selection is not fully known. The findings here suggest the ongoing evolutionary plasticity of modern humans at the genetic level and also partly provide insights into common human knockouts. PMID:26932450

  14. Premature termination codons in modern human genomes.

    PubMed

    Fujikura, Kohei

    2016-01-01

    The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which indicate a human knockout. From a total of 7595 participants from two population exome projects, 246 PTCs were found where natural selection has resulted in new alleles with a high frequency (from 1% to 96%) of derived alleles and various levels of population differentiation (FST = 0.00139-0.626). The PTC genes formed protein and regulatory networks limited to 15 biological processes or gene families, of which seven categories were previously unreported. PTC mutations have a strong tendency to be introduced into members of the same gene family, even during modern human evolution, although the exact nature of the selection is not fully known. The findings here suggest the ongoing evolutionary plasticity of modern humans at the genetic level and also partly provide insights into common human knockouts. PMID:26932450

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

    PubMed

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-01

    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. PMID:26341535

  16. 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites.

    PubMed

    Keku, Temitope; Millikan, Robert; Worley, Kendra; Winkel, Scott; Eaton, Allison; Biscocho, Lorna; Martin, Christopher; Sandler, Robert

    2002-12-01

    We evaluated polymorphisms in methylenetetrahydrofolate reductase (MTHFR), folate intake and alcohol consumption in relation to risk of colon cancer in a population-based case-control study in North Carolina. The study included 555 cases (244 African Americans and 311 whites) and 875 controls (331 African Americans and 544 whites). Total folate intake of <400 versus > or =400 microg/day showed a weak positive association with colon cancer among both African Americans [adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.0-2.0] and whites (OR = 1.6, 95% CI = 1.2-2.2). No association was observed with use of alcohol. Compared with wild-type genotypes, there was no association between the low activity MTHFR codon 677 TT genotype and colon cancer, but the low activity codon 1298 CC genotype was inversely associated with colon cancer in whites (OR = 0.5, 95% CI = 0.3-0.9). Unlike previous studies, we did not observe a strong protective effect of the codon 677 TT low-activity genotype when folate intake was high. Instead, we observed an increased risk of colon cancer when folate intake was low for participants with wild- type genotypes. Adjusted ORs for the combined effects of codon 677 CC and codon 1298 AA genotypes and folate intake <400 microg/day were 1.9 (95% CI = 1.1-3.4) in African Americans and 2.5 (95% CI = 1.2-5.2) in whites. Our results suggest that variation at MTHFR codon 1298 (within the COOH-terminal region) may be more important for colon cancer than variation at codon 677 (NH(2)-terminal region), and in populations where folate intake is low, wild-type MTHFR activity may increase risk for colon cancer. PMID:12496052

  17. Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

    PubMed Central

    2013-01-01

    Background The human APOBEC3G (A3G) protein activity is associated with innate immunity against HIV-1 by inducing high rates of guanosines to adenosines (G-to-A) mutations (viz., hypermutation) in the viral DNA. If hypermutation is not enough to disrupt the reading frames of viral genes, it may likely increase the HIV-1 diversity. To counteract host innate immunity HIV-1 encodes the Vif protein that binds A3G protein and form complexes to be degraded by cellular proteolysis. Methods Here we studied the pattern of substitutions in the vif gene and its association with clinical status of HIV-1 infected individuals. To perform the study, unique vif gene sequences were generated from 400 antiretroviral-naïve individuals. Results The codon pairs: 78–154, 85–154, 101–157, 105–157, and 105–176 of vif gene were associated with CD4+ T cell count lower than 500 cells per mm3. Some of these codons were located in the 81LGQGVSIEW89 region and within the BC-Box. We also identified codons under positive selection clustered in the N-terminal region of Vif protein, between 21WKSLVK26 and 40YRHHY44 regions (i.e., 31, 33, 37, 39), within the BC-Box (i.e., 155, 159) and the Cullin5-Box (i.e., 168) of vif gene. All these regions are involved in the Vif-induced degradation of A3G/F complexes and the N-terminal of Vif protein binds to viral and cellular RNA. Conclusions Adaptive evolution of vif gene was mostly to optimize viral RNA binding and A3G/F recognition. Additionally, since there is not a fully resolved structure of the Vif protein, codon pairs associated with CD4+ T cell count may elucidate key regions that interact with host cell factors. Here we identified and discriminated codons under positive selection and codons under functional constraint in the vif gene of HIV-1. PMID:23578255

  18. 20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL ...

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

    20. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, ARCH DETAIL SHOWING BRICK ARCH FOR MAIN SPAN AND STONE VOUSSOIRS. VIEW W. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

  19. Genetic Code Expansion by Degeneracy Reprogramming of Arginyl Codons.

    PubMed

    Lee, Ki Baek; Hou, Chen Yuan; Kim, Chae-Eun; Kim, Dong-Myung; Suga, Hiroaki; Kang, Taek Jin

    2016-07-01

    The genetic code in most organisms codes for 20 proteinogenic amino acids or translation stop. In order to encode more than 20 amino acids in the coding system, one of stop codons is usually reprogrammed to encode a non-proteinogenic amino acid. Although this approach works, usually only one amino acid is added to the amino acid repertoire. In this study, we incorporated non-proteinogenic amino acids into a protein by using a sense codon. As all the codons are allocated in the universal genetic code, we destroyed all the tRNA(Arg) in a cell-free protein synthesis system by using a tRNA(Arg) -specific tRNase, colicin D. Then by supplementing the system with tRNACCU , the translation system was partially restored. Through this creative destruction, reprogrammable codons were successfully created in the system to encode modified lysines along with the 20 proteinogenic amino acids. PMID:27151886

  20. Mononucleotide and dinucleotide frequencies, and codon usage in poliovirion RNA.

    PubMed Central

    Rothberg, P G; Wimmer, E

    1981-01-01

    The polio type 1 (Mahoney) RNA sequence (1) has been analyzed in terms of the distribution of its mononucleotides, dinucleotides and trinucleotides (codons). The distribution of adenosine in the sequence is nonuniform, being lower at the 5' end and higher at the 3' end. The dinucleotide CG is relatively rare and the dinucleotides UG and CA are relatively more common than expected. Codon usage is decidedly nonrandom. Codons containing CG are avoided and those ending in adenosine are favored. The asymmetric use of mononucleotides, dinucleotides and codons in polio RNA is unexplained at the present time although the lowered CG frequency may be the result of a DNA origin for polio RNA. PMID:6275352

  1. Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics.

    PubMed

    Lin, Kui; Kuang, Yuyu; Joseph, Jeremiah S; Kolatkar, Prasanna R

    2002-06-01

    Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVM(light). Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms. PMID:12034849

  2. Early Acute Antibody-Mediated Rejection of a Negative Flow Crossmatch 3rd Kidney Transplant with Exclusive Disparity at HLA-DP

    PubMed Central

    Mierzejewska, Beata; Schroder, Paul M.; Baum, Caitlin E.; Blair, Annette; Smith, Connie; Duquesnoy, Rene J.; Marrari, Marilyn; Gohara, Amira; Malhotra, Deepak; Kaw, Dinkar; Liwski, Robert; Rees, Michael A.; Stepkowski, Stanislaw

    2014-01-01

    Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA. PMID:24755353

  3. Key for protein coding sequences identification: computer analysis of codon strategy.

    PubMed Central

    Rodier, F; Gabarro-Arpa, J; Ehrlich, R; Reiss, C

    1982-01-01

    The signal qualifying an AUG or GUG as an initiator in mRNAs processed by E. coli ribosomes is not found to be a systematic, literal homology sequence. In contrast, stability analysis reveals that initiators always occur within nucleic acid domains of low stability, for which a high A/U content is observed. Since no aminoacid selection pressure can be detected at N-termini of the proteins, the A/U enrichment results from a biased usage of the code degeneracy. A computer analysis is presented which allows easy detection of the codon strategy. N-terminal codons carry rather systematically A or U in third position, which suggests a mechanism for translation initiation and helps to detect protein coding sequences in sequenced DNA. PMID:7038623

  4. Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis

    PubMed Central

    Jacob, Etai; Unger, Ron; Horovitz, Amnon

    2015-01-01

    Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined. DOI: http://dx.doi.org/10.7554/eLife.08932.001 PMID:26371555

  5. The NEMO Mutation Creating the Most-Upstream Premature Stop Codon Is Hypomorphic Because of a Reinitiation of Translation

    PubMed Central

    Puel, Anne; Reichenbach, Janine; Bustamante, Jacinta; Ku, Cheng-Lung; Feinberg, Jacqueline; Döffinger, Rainer; Bonnet, Marion; Filipe-Santos, Orchidée; Beaucoudrey, Ludovic de; Durandy, Anne; Horneff, Gerd; Novelli, Francesco; Wahn, Volker; Smahi, Asma; Israel, Alain; Niehues, Tim; Casanova, Jean-Laurent

    2006-01-01

    Amorphic mutations in the NF-κB essential modulator (NEMO) cause X-dominant incontinentia pigmenti, which is lethal in males in utero, whereas hypomorphic mutations cause X-recessive anhidrotic ectodermal dysplasia with immunodeficiency, a complex developmental disorder and life-threatening primary immunodeficiency. We characterized the NEMO mutation 110_111insC, which creates the most-upstream premature translation termination codon (at codon position 49) of any known NEMO mutation. Surprisingly, this mutation is associated with a pure immunodeficiency. We solve this paradox by showing that a Kozakian methionine codon located immediately downstream from the insertion allows the reinitiation of translation. The residual production of an NH2-truncated NEMO protein was sufficient for normal fetal development and for the subsequent normal development of skin appendages but was insufficient for the development of protective immune responses. PMID:16532398

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

    PubMed

    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. PMID:26797435

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

    PubMed Central

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

    2015-01-01

    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. PMID:26797435

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

    PubMed Central

    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. PMID:26840415

  9. [The Original Formulation for Toso-shu (Tusujiu), Created by the 3rd Century Chinese Physician, Hua Tuo].

    PubMed

    Mouri, Chika; Mikage, Masayuki

    2015-01-01

    The original formulation for "Tusujiu," which Japanese people still consume on the morning of January 1st, was created by Hua Tuo, but has not been studied in detail. The book Huatuo Shenyi Bizhuan, found in 1918, describes a concoction, "Biyijiu," that shows great similarity to the current Tusujiu; the ingredients for Biyijiu being rhubarb, atractylodes rhizome, cinnamon bark, platycodon root, zanthoxylum fruit, processed aconite root and smilax rhizome. The procedures for preparing and drinking it are to "pound the ingredients and then put them into a silk bag dyed with madder. During the daytime of the last day of the year, hang the bag in a well to soften the powder. Take the bag out early in the morning of the next day, the first day of the year. Heat the bag in fermented liquor until simmering. Drink the liquid with all family members, doing so while facing east. If one person drinks it, there will be no disease in the family. If the whole family drinks it, there will be no disease in their neighborhood in an area of one square 'li'. In this study, to determine the original formulation for Tusujiu, we examined a number of ancient medical texts from the 3rd to the 13th century that discuss Biyijiu and Tusujiu. As a result, we concluded that "Biyijiu" is likely to be the original formulation developed by Hua Tuo. PMID:26427101

  10. Altered differential hemocyte count in 3rd instar larvae of Drosophila melanogaster as a response to chronic exposure of Acephate

    PubMed Central

    Rajak, Prem; Dutta, Moumita

    2015-01-01

    Acephate, an organophosphate (OP) pesticide, was used to investigate the effects of its chronic exposure on hemocyte abundance in a non-target dipteran insect Drosophila melanogaster. For this purpose, six graded concentrations ranging from 1 to 6 μg/ml were selected, which are below the reported residual values (up to 14 μg/ml) of the chemical. 1st instar larvae were fed with these concentrations up to the 3rd instar stage and accordingly hemolymph smears from these larvae were prepared for differential hemocyte count. Three types of cells are found in Drosophila hemolymph, namely, plasmatocytes, lamellocytes and crystal cells. Plasmatocyte count was found to decrease with successive increase in treatment concentrations. Crystal cells showed an increasing trend in their number. Though the number of lamellocytes was very low, a bimodal response was noticed. Lamellocyte number was found to increase with the initial three concentrations, followed by a dose dependent reduction in their number. As hemocytes are directly linked to the immune system of fruit flies, fluctuations in normal titer of these cells may affect insect immunity. Hemocytes share homologies in their origin and mode of action with the immune cells of higher organisms including man. Thus the present findings suggest that immune cells of humans and other organisms may be affected adversely under chronic exposure to Acephate. PMID:27486365

  11. Organizational Support for the 3rd Summer Institute on Complex Plasmas, July 30 – August 8, 2012

    SciTech Connect

    Lopez, Jose L.

    2012-07-01

    This grant provided partial funds for American graduate students to attend the 3rd Graduate Summer Institute on Complex Plasmas, which was held from July 30 to August 8, 2012 at Seton Hall University in South Orange, New Jersey. The Graduate Summer Institute is a topical series of instructional workshops held bi-annually on the emerging field of complex plasmas that is jointly organized through a collaboration between American and German-European Union plasmas researchers. This specialized program brings together many of the world's leading researchers in the specialized area of complex plasmas, who freely provide instructional lectures and tutorials on the most recent research and discoveries done in this branch of plasma science. The partial funds provided by this grant helped support the travel and accommodation expenses of the participating American students and tutorial instructors. Partial funds further supported the travel and accommodation of three renown American plasma researchers that provided educational tutorials to the thirty-eight participating students from the United States, Europe, and Asia. The organized program afforded a unique opportunity for the participating American graduate students to learn about and engage more deeply in an area of plasma science that is not studied in any of the graduate educational curriculums provided by universities in the United States of America. The educational experience offered by this program provided the necessary knowledge needed by future American plasma researchers to keep the national plasma research effort on the cutting-edge and keep the national plasma community as a global leader.

  12. Evaluation of a model of dissertation supervision for 3rd year B.Sc. undergraduate nursing students.

    PubMed

    Scholefield, Donna; Cox, Georgina

    2016-03-01

    All English universities now offer an all degree undergraduate nursing programme. Many currently use an individual supervision model to support final year dissertation students, but with increased numbers and limited resources new models of supervision are needed. This study evaluated a mixed (group and individual) model of dissertation supervision to determine its effectiveness for a large group of undergraduate nursing students. A sample of 3rd year students and their supervisors were selected from one large university. An evaluation survey was conducted using anonymous internet-based questionnaires and focus groups. The data was analysed using Survey Monkey, SPSS and thematic analysis. A 51% (n = 56/110) response rate (students) and 65% (n = 24/37) for supervisors was obtained. The majority of students and supervisors were satisfied with the new model. There was a mixed response to the group workshops and supervision groups. Three themes emerged from the qualitative data: engaging with the process, motivation to supervise and valuing the process. The supervision process is a struggle but both parties gained considerably from going through the process. In conclusion, a mixed model of supervision together with a range of other learning resources can be an effective approach in supporting students through the dissertation process. PMID:26700648

  13. The 3rd Canadian Symposium on Hepatitis C Virus: expanding care in the interferon-free era.

    PubMed

    MacParland, Sonya A; Bilodeau, Marc; Grebely, Jason; Bruneau, Julie; Cooper, Curtis; Klein, Marina; Sagan, Selena; Choucha, Norma; Balfour, Louise; Bialystok, Frank; Krajden, Mel; Raven, Jennifer; Roberts, Eve; Russell, Rodney; Houghton, Michael; Tyrrell, D Lorne; Feld, Jordan J

    2014-10-01

    Hepatitis C virus (HCV) currently infects approximately 250,000 individuals in Canada and causes more years of life lost than any other infectious disease in the country. In August 2011, new therapies were approved by Health Canada that have achieved higher response rates among those treated, but are poorly tolerated. By 2014⁄2015, short-course, well-tolerated treatments with cure rates >95% will be available. However, treatment uptake is poor due to structural, financial, geographical, cultural and social barriers. As such, 'Barriers to access to HCV care in Canada' is a crucial topic that must be addressed to decrease HCV disease burden and potentially eliminate HCV in Canada. Understanding how to better care for HCV-infected individuals requires integration across multiple disciplines including researchers, clinical services and policy makers to address the major populations affected by HCV including people who inject drugs, baby boomers, immigrants and Aboriginal and⁄or First Nations people. In 2012, the National CIHR Research Training Program in Hepatitis C organized the 1st Canadian Symposium on Hepatitis C Virus (CSHCV) in Montreal, Quebec. The 2nd CSHCV was held in 2013 in Victoria, British Columbia. Both symposia were highly successful, attracting leading international faculty with excellent attendance leading to dialogue and knowledge translation among attendees of diverse backgrounds. The current article summarizes the 3rd CSHCV, held February 2014, in Toronto, Ontario. PMID:25314353

  14. The 3rd Canadian Symposium on Hepatitis C Virus: Expanding care in the interferon-free era

    PubMed Central

    MacParland, Sonya A; Bilodeau, Marc; Grebely, Jason; Bruneau, Julie; Cooper, Curtis; Klein, Marina; Sagan, Selena M; Choucha, Norma; Balfour, Louise; Bialystok, Frank; Krajden, Mel; Raven, Jennifer; Roberts, Eve; Russell, Rodney; Houghton, Michael; Tyrrell, D Lorne; Feld, Jordan J

    2014-01-01

    Hepatitis C virus (HCV) currently infects approximately 250,000 individuals in Canada and causes more years of life lost than any other infectious disease in the country. In August 2011, new therapies were approved by Health Canada that have achieved higher response rates among those treated, but are poorly tolerated. By 2014/2015, short-course, well-tolerated treatments with cure rates >95% will be available. However, treatment uptake is poor due to structural, financial, geographical, cultural and social barriers. As such, ‘Barriers to access to HCV care in Canada’ is a crucial topic that must be addressed to decrease HCV disease burden and potentially eliminate HCV in Canada. Understanding how to better care for HCV-infected individuals requires integration across multiple disciplines including researchers, clinical services and policy makers to address the major populations affected by HCV including people who inject drugs, baby boomers, immigrants and Aboriginal and/or First Nations people. In 2012, the National CIHR Research Training Program in Hepatitis C organized the 1st Canadian Symposium on Hepatitis C Virus (CSHCV) in Montreal, Quebec. The 2nd CSHCV was held in 2013 in Victoria, British Columbia. Both symposia were highly successful, attracting leading international faculty with excellent attendance leading to dialogue and knowledge translation among attendees of diverse backgrounds. The current article summarizes the 3rd CSHCV, held February 2014, in Toronto, Ontario. PMID:25314353

  15. 3rd Quarter Transportation Report FY 2014: Radioactive Waste Shipments to and from the Nevada National Security Site (NNSS)

    SciTech Connect

    Gregory, Louis

    2014-09-20

    This report satisfies the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) commitment to prepare a quarterly summary report of radioactive waste shipments to the Nevada National Security Site (NNSS) Radioactive Waste Management Complex (RWMC) at Area 5. There were no shipments sent for offsite treatment and returned to the NNSS this quarter. This report summarizes the 3rd quarter of Fiscal Year (FY) 2014 low-level radioactive waste (LLW) and mixed low-level radioactive waste (MLLW) shipments. This report also includes annual summaries for FY 2014 in Tables 4 and 5. Tabular summaries are provided which include the following: Sources of and carriers for LLW and MLLW shipments to and from the NNSS; Number and external volume of LLW and MLLW shipments; Highway routes used by carriers; and Incident/accident data applicable to LLW and MLLW shipments. In this report shipments are accounted for upon arrival at the NNSS, while disposal volumes are accounted for upon waste burial. The disposal volumes presented in this report do not include minor volumes of non-radioactive materials that were approved for disposal. Volume reports showing cubic feet generated using the Low-Level Waste Information System may vary slightly due to differing rounding conventions.

  16. Effects of using relaxation breathing training to reduce music performance anxiety in 3rd to 6th graders.

    PubMed

    Su, Yu-Huei; Luh, Jer-Junn; Chen, Hsin-I; Lin, Chao-Chen; Liao, Miin-Jiun; Chen, Heng-Shuen

    2010-06-01

    The current study examined the effects of applying relaxation breathing training (RBT) as a means to reduce music performance anxiety (MPA) in young, talented musicians. A group of 59 young musicians from 3rd to 6th grade participated in this study, and all of them started RBT twice a week for 2 months prior to the examination. Four tests--2 mos, 1 mos, half an hour and 5 min before the examination--were conducted to examine the level of MPA after the application of RBT. Results show that the degree of MPA 5 min before the trial was lower than the degree of performance anxiety half an hour before the jury (t = -3.683, p < 0.01), which indicated that the RBT was associated with a decrease in MPA. Although a series of RBT exercises was applied, results indicated that when approaching the date of examination, the degree of performance anxiety still increased and reached its maximum half an hour before the jury. The recommendation for future studies is to combine the application of RBT with other methods to expand its effect in reducing MPA. PMID:20795337

  17. InAs/GaSb type II superlattices for advanced 2nd and 3rd generation detectors

    NASA Astrophysics Data System (ADS)

    Walther, Martin; Rehm, Robert; Schmitz, Johannes; Fleissner, Joachim; Rutz, Frank; Kirste, Lutz; Scheibner, Ralf; Wendler, Joachim; Ziegler, Johann

    2010-01-01

    InAs/GaSb short-period superlattices (SL) based on GaSb, InAs and AlSb have proven their great potential for high performance infrared detectors. Lots of interest is currently focused on the development of short-period InAs/GaSb SLs for advanced 2nd and 3rd generation infrared detectors between 3 - 30 μm. For the fabrication of mono- and bispectral thermal imaging systems in the mid-wavelength infrared region (MWIR) a manufacturable technology for high responsivity thermal imaging systems has been developed. InAs/GaSb short-period superlattices can be fabricated with up to 1000 periods in the intrinsic region without revealing diffusion limited behavior. This enables the fabrication of InAs/GaSb SL camera systems with high responsivity comparable to state of the art CdHgTe and InSb detectors. The material system is also ideally suited for the fabrication of dual-color MWIR/MWIR InAs/GaSb SL camera systems with high quantum efficiency for missile approach warning systems with simultaneous and spatially coincident detection in both spectral channels.

  18. Analysis of time-variant quadratic phase couplings in the tracé alternant EEG by recursive estimation of 3rd-order time-frequency distributions.

    PubMed

    Helbig, Marko; Schwab, Karin; Leistritz, Lutz; Eiselt, Michael; Witte, Herbert

    2006-10-15

    The quantification of transient quadratic phase couplings (QPC) by means of time-variant bispectral analysis is a useful approach to explain several interrelations between signal components. A generalized recursive estimation approach for 3rd-order time-frequency distributions (3rd-order TFD) is introduced. Based on 3rd-order TFD, time-variant estimations of biamplitude (BA), bicoherence (BC) and phase bicoherence (PBC) can be derived. Different smoothing windows and local moment functions for an optimization of the estimation properties are investigated and compared. The methods are applied to signal simulations and EEG signals, and it can be shown that the new time-variant bispectral analysis results in a reliable quantification of QPC in the tracé alternant EEG of healthy neonates. PMID:16737739

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

    PubMed

    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. PMID

  20. PREFACE: Special section featuring selected papers from the 3rd International Workshop on Numerical Modelling of High Temperature Superconductors Special section featuring selected papers from the 3rd International Workshop on Numerical Modelling of High Temperature Superconductors

    NASA Astrophysics Data System (ADS)

    Granados, Xavier; Sánchez, Àlvar; López-López, Josep

    2012-10-01

    The development of superconducting applications and superconducting engineering requires the support of consistent tools which can provide models for obtaining a good understanding of the behaviour of the systems and predict novel features. These models aim to compute the behaviour of the superconducting systems, design superconducting devices and systems, and understand and test the behavior of the superconducting parts. 50 years ago, in 1962, Charles Bean provided the superconducting community with a model efficient enough to allow the computation of the response of a superconductor to external magnetic fields and currents flowing through in an understandable way: the so called critical-state model. Since then, in addition to the pioneering critical-state approach, other tools have been devised for designing operative superconducting systems, allowing integration of the superconducting design in nearly standard electromagnetic computer-aided design systems by modelling the superconducting parts with consideration of time-dependent processes. In April 2012, Barcelona hosted the 3rd International Workshop on Numerical Modelling of High Temperature Superconductors (HTS), the third in a series of workshops started in Lausanne in 2010 and followed by Cambridge in 2011. The workshop reflected the state-of-the-art and the new initiatives of HTS modelling, considering mathematical, physical and technological aspects within a wide and interdisciplinary scope. Superconductor Science and Technology is now publishing a selection of papers from the workshop which have been selected for their high quality. The selection comprises seven papers covering mathematical, physical and technological topics which contribute to an improvement in the development of procedures, understanding of phenomena and development of applications. We hope that they provide a perspective on the relevance and growth that the modelling of HTS superconductors has achieved in the past 25 years.

  1. Enhanced expression of codon optimized interferon gamma in CHO cells.

    PubMed

    Chung, Bevan Kai-Sheng; Yusufi, Faraaz N K; Mariati; Yang, Yuansheng; Lee, Dong-Yup

    2013-09-10

    The human interferon-gamma (IFN-γ) is a potential drug candidate for treating various diseases due to its immunomodulatory properties. The efficient production of this protein can be achieved through a popular industrial host, Chinese hamster ovary (CHO) cells. However, recombinant expression of foreign proteins is typically suboptimal possibly due to the usage of non-native codon patterns within the coding sequence. Therefore, we demonstrated the application of a recently developed codon optimization approach to design synthetic IFN-γ coding sequences for enhanced heterologous expression in CHO cells. For codon optimization, earlier studies suggested to establish the target usage distribution pattern in terms of selected design parameters such as individual codon usage (ICU) and codon context (CC), mainly based on the host's highly expressed genes. However, our RNA-Seq based transcriptome profiling indicated that the ICU and CC distribution patterns of different gene expression classes in CHO cell are relatively similar, unlike other microbial expression hosts, Escherichia coli and Saccharomyces cerevisiae. This finding was further corroborated through the in vivo expression of various ICU and CC optimized IFN-γ in CHO cells. Interestingly, the CC-optimized genes exhibited at least 13-fold increase in expression level compared to the wild-type IFN-γ while a maximum of 10-fold increase was observed for the ICU-optimized genes. Although design criteria based on individual codons, such as ICU, have been widely used for gene optimization, our experimental results suggested that codon context is relatively more effective parameter for improving recombinant IFN-γ expression in CHO cells. PMID:23876479

  2. Recognition of the amber UAG stop codon by release factor RF1

    SciTech Connect

    Korostelev, Andrei; Zhu, Jianyu; Asahara, Haruichi; Noller, Harry F.

    2010-08-23

    We report the crystal structure of a termination complex containing release factor RF1 bound to the 70S ribosome in response to an amber (UAG) codon at 3.6-{angstrom} resolution. The amber codon is recognized in the 30S subunit-decoding centre directly by conserved elements of domain 2 of RF1, including T186 of the PVT motif. Together with earlier structures, the mechanisms of recognition of all three stop codons by release factors RF1 and RF2 can now be described. Our structure confirms that the backbone amide of Q230 of the universally conserved GGQ motif is positioned to contribute directly to the catalysis of the peptidyl-tRNA hydrolysis reaction through stabilization of the leaving group and/or transition state. We also observe synthetic-negative interactions between mutations in the switch loop of RF1 and in helix 69 of 23S rRNA, revealing that these structural features interact functionally in the termination process. These findings are consistent with our proposal that structural rearrangements of RF1 and RF2 are critical to accurate translation termination.

  3. Electrocradiographic Qrs Axis, Q Wave and T-wave Changes in 2nd and 3rd Trimester of Normal Pregnancy

    PubMed Central

    S., Chandrasekharappa; Brid, S.V

    2014-01-01

    Background: Pregnancy although a physiological phenomena affects all the functions of the maternal body and brings about remarkable changes in the cardiovascular system. The cardiovascular changes and many of the physiological adaptations of normal pregnancy alter the physical findings thus, sometimes misleading the diagnosis of heart disease. Pregnancy also brings about various changes in the electrocardiogram, further confusing with that of heart disease. This study is undertaken to highlight the effect of normal pregnancy on the QRS axis, Q wave and T-wave of the Electrocardiogram and thereby helps us to distinguish it from that of pathological changes. Objectives: To study the effect of normal pregnancy on the QRS axis, Q wave and T-wave in the electrocardiogram and to compare with that of normal non pregnant women. Materials and Methods: Fifty normal pregnant women in 2nd and 3rd trimester each between 20– 35 y of age and 50 normal non pregnant women of the same age group were selected for the study. A 12 lead ECG was recorded by using ECG machine with special emphasis on QRS axis, Q wave and T-wave changes and all the parameters were analysed. Results: The ECG changes observed in our study include, deviation of QRS axis towards left as pregnancy advanced, significant increased incidence of occurrence of prominent Q waves in lead II, III and avF in pregnant group (p < 0.05 ) and, T-wave abnormalities like flat and inverted T-waves in lead III, V1 – V3 were more frequent in pregnant group ( p<0.05 ) than in non pregnant group. Conclusion:Normal pregnancy brings about various changes in ECG. These changes during pregnancy should be interpretated with caution by the physicians. It is necessary to understand the normal physiological changes which in turn help us in better management of those with cardiac disease. PMID:25386425

  4. Two-codon T-box riboswitch binding two tRNAs

    PubMed Central

    Saad, Nizar Y.; Stamatopoulou, Vassiliki; Brayé, Mélanie; Drainas, Denis; Stathopoulos, Constantinos; Becker, Hubert Dominique

    2013-01-01

    T-box riboswitches control transcription of downstream genes through the tRNA-binding formation of terminator or antiterminator structures. Previously reported T-boxes were described as single-specificity riboswitches that can bind specific tRNA anticodons through codon–anticodon interactions with the nucleotide triplet of their specifier loop (SL). However, the possibility that T-boxes might exhibit specificity beyond a single tRNA had been overlooked. In Clostridium acetobutylicum, the T-box that regulates the operon for the essential tRNA-dependent transamidation pathway harbors a SL with two potential overlapping codon positions for tRNAAsn and tRNAGlu. To test its specificity, we performed extensive mutagenic, biochemical, and chemical probing analyses. Surprisingly, both tRNAs can efficiently bind the SL in vitro and in vivo. The dual specificity of the T-box is allowed by a single base shift on the SL from one overlapping codon to the next. This feature allows the riboswitch to sense two tRNAs and balance the biosynthesis of two amino acids. Detailed genomic comparisons support our observations and suggest that “flexible” T-box riboswitches are widespread among bacteria, and, moreover, their specificity is dictated by the metabolic interconnection of the pathways under control. Taken together, our results support the notion of a genome-dependent codon ambiguity of the SLs. Furthermore, the existence of two overlapping codons imposes a unique example of tRNA-dependent regulation at the transcriptional level. PMID:23858450

  5. Factors impacting the aminoglycoside-induced UGA stop codon readthrough in selenoprotein translation.

    PubMed

    Martitz, Janine; Hofmann, Peter Josef; Johannes, Jörg; Köhrle, Josef; Schomburg, Lutz; Renko, Kostja

    2016-09-01

    Aminoglycosides (AG) are oligosaccharide antibiotics that interfere with the small ribosomal subunit in aerobic, Gram-negative bacteria, causing pathogen-destructing error rates in their protein biosynthesis. Aminoglycosides also induce mRNA misinterpretation in eukaryotic cells, especially of the UGA (Opal)-stop codon, albeit to a lower extent. UGA recoding is essentially required for the incorporation of selenocysteine (Sec) into growing selenoproteins during translation. Selenocysteine incorporation requires the presence of a selenoprotein-specific stem-loop structure within the 3'-untranslated region of the mRNA, the so-called Sec-insertion sequence (SECIS) element. Interestingly, selenoprotein genes differ in their SECIS-element sequence and in their UGA base context. We hypothesized that the SECIS-element and the specific codon context synergize in controlling the effects of AG on stop codon readthrough. To this end, the SECIS-elements of glutathione peroxidase 1, glutathione peroxidase 4 and selenoprotein P transcripts were cloned into a reporter system and analyzed in combination with different UGA codon contexts. Our results indicate that a cytosine in position 4 (directly downstream of UGA) confers strongest effects on both the Se- and AG-dependent readthrough. Overall selenoprotein biosynthesis rate depends on the Se-status, AG concentration and the specific SECIS-element present in the transcript. These findings help to get a better understanding for the susceptibility of different transcripts towards AG-mediated interference with the biosynthesis of functional Se-containing selenoproteins, and highlight the importance of the Se-status for successful selenoprotein biosynthesis under antibiotic therapy. PMID:27157664

  6. Impact of rare codons and the functional coproduction of rate-limiting tRNAs on recombinant protein production in Bacillus megaterium.

    PubMed

    Finger, Constanze; Gamer, Martin; Klunkelfuß, Saskia; Bunk, Boyke; Biedendieck, Rebekka

    2015-11-01

    The Gram-positive bacterium Bacillus megaterium was systematically developed for the plasmid-based production of recombinant proteins at the gram-per-liter scale. The amount of protein produced per cell was found strongly correlated to the codon usage of the heterologous gene of interest in comparison to the codon usage of B. megaterium. For analyzing the influence of rare codons on the translational efficiency and protein production in B. megaterium, a test system using the gene for the green fluorescent protein (GFP) as reporter was established. For this purpose, four consecutive identical codons were introduced into the 5' end of gfp and the resulting variations in GFP formation were quantified. Introduction of the rare codons GCC, CGG, and ACC for alanine, arginine, and threonine reduced GFP production 2.1-, 3.3-, and 1.7-fold in comparison to the favored codons GCU, CGU, and ACA, respectively. Coexpression of the corresponding rare codon tRNA (rctRNA) genes improved GFP production 4.2-, 2.7-, and 1.7-fold, respectively. The system was applied to the production of a formate dehydrogenase (FDH) from Mycobacterium vaccae and an extracellular hydrolase (TFH) from Thermobifida fusca. Coexpression of one to three different rctRNA genes resulted in an up to 18-fold increased protein production. Interestingly, rctRNA gene coexpression also elevated the production of M. vaccae FDH and T. fusca TFH from codon optimized genes, indicating a general positive effect by rctRNA gene overexpression on the protein production in B. megaterium. Thus, the basis for a B. megaterium enhanced production strain coexpressing rctRNA genes was laid. PMID:26138251

  7. An extra tRNAGly(U*CU) found in ascidian mitochondria responsible for decoding non-universal codons AGA/AGG as glycine.

    PubMed

    Kondow, A; Suzuki, T; Yokobori, S; Ueda, T; Watanabe, K

    1999-06-15

    Amino acid assignments of metazoan mitochondrial codons AGA/AGG are known to vary among animal species; arginine in Cnidaria, serine in invertebrates and stop in vertebrates. We recently found that in the mitochondria of the ascidian Halocynthia roretzi these codons are exceptionally used for glycine, and postulated that they are probably decoded by a tRNA(UCU). In order to verify this notion unambig-uously, we determined the complete RNA sequence of the mitochondrial tRNA(UCU) presumed to decode codons AGA/AGG in the ascidian mitochondria, and found it to have an unidentified U derivative at the anticodon first position. We then identified the amino acids attached to the tRNA(U*CU), as well as to the conventional tRNAGly(UCC) with an unmodified U34, in vivo. The results clearly demonstrated that glycine was attached to both tRNAs. Since no other tRNA capable of decoding codons AGA/AGG has been found in the mitochondrial genome, it is most probable that this tRNA(U*CU) does actually translate codons AGA/AGG as glycine in vivo. Sequencing of tRNASer(GCU), which is thought to recognize only codons AGU/AGC, revealed that it has an unmodified guanosine at position 34, as is the case with vertebrate mitochondrial tRNASer(GCU) for codons AGA/AGG. It was thus concluded that in the ascidian, codons AGU/AGC are read as serine by tRNASer(GCU), whereas AGA/AGG are read as glycine by an extra tRNAGly(U*CU). The possible origin of this unorthodox genetic code is discussed. PMID:10352185

  8. Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae.

    PubMed

    Li, Xiuzhang; Song, Hui; Kuang, Yu; Chen, Shuihong; Tian, Pei; Li, Chunjie; Nan, Zhibiao

    2016-01-01

    Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C. PMID:27428961

  9. Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae

    PubMed Central

    Li, Xiuzhang; Song, Hui; Kuang, Yu; Chen, Shuihong; Tian, Pei; Li, Chunjie; Nan, Zhibiao

    2016-01-01

    Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C. PMID:27428961

  10. An Engineered Rare Codon Device for Optimization of Metabolic Pathways

    PubMed Central

    Wang, You; Li, Chunying; Khan, Md. Rezaul Islam; Wang, Yushu; Ruan, Yunfeng; Zhao, Bin; Zhang, Bo; Ma, Xiaopan; Zhang, Kaisi; Zhao, Xiwen; Ye, Guanhao; Guo, Xizhi; Feng, Guoyin; He, Lin; Ma, Gang

    2016-01-01

    Rare codons generally arrest translation due to rarity of their cognate tRNAs. This property of rare codons can be utilized to regulate protein expression. In this study, a linear relationship was found between expression levels of genes and copy numbers of rare codons inserted within them. Based on this discovery, we constructed a molecular device in Escherichia coli using the rare codon AGG, its cognate tRNA (tRNAArg (CCU)), modified tRNAAsp (GUC → CCU), and truncated aspartyl-tRNA synthetase (TDRS) to switch the expression of reporter genes on or off as well as to precisely regulate their expression to various intermediate levels. To underscore the applicability of our work, we used the rare codon device to alter the expression levels of four genes of the fatty acid synthesis II (FASII) pathway (i.e. fabZ, fabG, fabI, and tesA’) in E. coli to optimize steady-state kinetics, which produced nearly two-fold increase in fatty acid yield. Thus, the proposed method has potential applications in regulating target protein expression at desired levels and optimizing metabolic pathways by precisely tuning in vivo molar ratio of relevant enzymes. PMID:26852704

  11. Implications of Technology for Teaching and Learning. Annual Professional Education Seminar of Central States Colleges and Universities (3rd, November, 1967).

    ERIC Educational Resources Information Center

    Woodruff, Asahel; Froyen, Len

    This report of the proceedings of the 3rd Annual Professional Education Seminar of the Central States Colleges and Universities centers upon the implications of technology for teaching and learning and contains addresses delivered, including "Some Concerns Related to Technology in Education," by Len Froyen; and "Implications of Technology for…

  12. The Relationship between Perceived and Ideal Body Size and Body Mass Index in 3rd-Grade Low Socioeconomic Hispanic Children

    ERIC Educational Resources Information Center

    Fisher, Allison; Lange, Mary Anne; Young-Cureton, Virginia; Canham, Daryl

    2005-01-01

    Very little is known about body satisfaction among minority children. This study examined the relationship between perceived and actual body size and Body Mass Index among 43 low-socioeconomic Hispanic 3rd-graders. Researchers measured participants' Body Mass Index; students self-reported Perceived Ideal Self Image and Perceived Actual Self Image…

  13. Midwest Child-Parent Center (CPC) PreK-3rd Grade School Reform Model: Impacts on Child and Family Outcomes over Time

    ERIC Educational Resources Information Center

    Gaylor, Erika; Spiker, Donna; Wei, Xin; Lease, Erin; Reynolds, Arthur

    2015-01-01

    This presentation reports on the goals and preliminary outcomes of the Child-Parent Centers (CPC) Expansion Project, which is a PreK to 3rd grade school reform model aimed at improving the short- and long-term outcomes of participating children and families. The model provides continuous education and family support services to schools serving a…

  14. Design, synthesis, and testing toward a 57-codon genome.

    PubMed

    Ostrov, Nili; Landon, Matthieu; Guell, Marc; Kuznetsov, Gleb; Teramoto, Jun; Cervantes, Natalie; Zhou, Minerva; Singh, Kerry; Napolitano, Michael G; Moosburner, Mark; Shrock, Ellen; Pruitt, Benjamin W; Conway, Nicholas; Goodman, Daniel B; Gardner, Cameron L; Tyree, Gary; Gonzales, Alexandra; Wanner, Barry L; Norville, Julie E; Lajoie, Marc J; Church, George M

    2016-08-19

    Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms. PMID:27540174

  15. Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons

    NASA Astrophysics Data System (ADS)

    Lind, Christoffer; Sund, Johan; Åqvist, Johan

    2013-12-01

    A key feature of mitochondrial translation is the reduced number of transfer RNAs and reassignment of codons. For human mitochondria, a major unresolved problem is how the set of stop codons are decoded by the release factors mtRF1a and mtRF1. Here we present three-dimensional structural models of human mtRF1a and mtRF1 based on their homology to bacterial RF1 in the codon recognition domain, and the strong conservation between mitochondrial and bacterial ribosomal RNA in the decoding region. Sequence changes in the less homologous mtRF1 appear to be correlated with specific features of the mitochondrial rRNA. Extensive computer simulations of the complexes with the ribosomal decoding site show that both mitochondrial factors have similar specificities and that neither reads the putative vertebrate stop codons AGA and AGG. Instead, we present a structural model for a mechanism by which the ICT1 protein causes termination by sensing the presence of these codons in the A-site of stalled ribosomes.

  16. PREFACE: 3rd International Conference on Science & Engineering in Mathematics, Chemistry and Physics 2015 (ScieTech 2015)

    NASA Astrophysics Data System (ADS)

    Gaol, F. L.

    2015-06-01

    The 3rd International Conference on Science & Engineering in Mathematics, Chemistry and Physics 2015 (ScieTech 2015), was held at The Westin Resort Nusa Dua, Bali on 31 January - 1 February 2015. The ScieTech 2015 conference is aimed to bring together researchers, engineers and scientists from around the world. ScieTech 2015 is placed on promoting interaction between the theoretical, experimental, and applied communities, so that a high level exchange is achieved in new and emerging areas within mathematics, chemistry and physics. As we already know that science and technology have brought tremendous benefits for human civilization. People are becoming healthier, wealthier, better educated, more peaceful, increasingly connected, and living longer. Of course, science and technology provide many answers to global challenges, but we will face more complex problems in the next decade due to increasing world population, limitation of energy, and climate change. Therefore, researchers should be more active in conducting research that enables collaboration between one and the others. Interdisciplinary cooperation is absolutely necessary in order to create a smart system for solving the global problems. We need a global and general long-term view of the future with long-range goals for solving complex problems in next decade. Therefore the conference was held to be a forum for researchers from different disciplines to start collaborating and conducting research that provides a solution to the global issues. The theme of ScieTech 2015 was ''The interdisciplinary Application between Mathematics, Chemistry and Physics to enhance the Quality of Life''. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting conference program as well as the invited and plenary speakers. This year, we received 197 papers and after rigorous review, 59 papers were accepted. The participants came from 19

  17. Effect on Physical Activity of a Randomized Afterschool Intervention for Inner City Children in 3rd to 5th Grade

    PubMed Central

    Crouter, Scott E.; de Ferranti, Sarah D.; Whiteley, Jessica; Steltz, Sarah K.; Osganian, Stavroula K.; Feldman, Henry A.; Hayman, Laura L.

    2015-01-01

    Background Less than 45% of U.S. children meet the 60 min.d-1 physical activity (PA) guideline. Structured after-school PA programing is one approach to help increase activity levels. This study aimed to evaluate the feasibility and short-term impact of a supervised after-school PA and nutrition education program on activity levels. Methods Forty-two 3rd-5th graders from an inner-city school in Boston, MA were randomly assigned to a 10-wk after-school program of either: 1) weekly nutrition education, or 2) weekly nutrition education plus supervised PA 3 d.wk-1 at a community-based center. At baseline and follow-up, PA was measured using accelerometry and fitness (VO2max) was estimated using the PACER 15-m shuttle run. Additional measures obtained were non-fasting finger stick total cholesterol (TC) and glucose levels, waist circumference (WC), body mass index (BMI), percent body fat (%BF), and blood pressure (BP). Values are presented as mean±SE, unless noted otherwise. Results Thirty-six participants completed the study (mean±SD; age 9.7±0.9 years). Participants attended >80% of the sessions. After adjusting for accelerometer wear time and other design factors, light and moderate-to-vigorous PA (MVPA) increased in the nutrition+PA group (+21.5±14.5 and +8.6±8.0 min.d-1, respectively) and decreased in the nutrition only group (-35.2±16.3 and -16.0±9.0 min.d-1, respectively); mean difference between groups of 56.8±21.7 min.d-1 (light PA, p = 0.01) and 24.5±12.0 min.d-1 (MVPA, p = 0.04). Time spent in sedentary behaviors declined in the nutrition+PA group (-14.8±20.7 min.d-1) and increased in the nutrition only group (+55.4±23.2 min.d-1); mean difference between groups of -70.2±30.9 min.d-1 (p = 0.02). Neither group showed changes in TC, BP, WC, %BF, BMI percentile, or fitness (p>0.05). Conclusions The supervised afterschool community-based nutrition and PA program was well accepted and had high attendance. The changes in light PA and MVPA has potential

  18. PREFACE: 3rd International Conference on Geological, Geographical, Aerospace and Earth Science 2015 (AeroEarth 2015)

    NASA Astrophysics Data System (ADS)

    Gaol, F. L.

    2016-02-01

    The 3rd International Conferences on Geological, Geographical, Aerospaces and Earth Sciences 2015 (AeroEarth 2015), was held at The DoubleTree Hilton, Jakarta, Indonesia during 26 - 27 September 2015. The 1st AeoroEarth was held succefully in Jakarta in 2013. The success continued to The 2nd AeroEarth 2014 that was held in Kuta Bali, Indonesia. The publications were published by EES IOP in http://iopscience.iop.org/1755-1315/19/1 and http://iopscience.iop.org/1755-1315/23/1 respectively. The AeroEarth 2015 conference aims to bring together researchers, engineers and scientists from around the world. Through research and development, Earth's scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. The theme of AeroEarth 2015 is ''Earth and Aerospace Sciences : Challenges and Opportunities'' Earth provides resources and the exact conditions to make life possible. However, with the advent of technology and industrialization, the Earth's resources are being pushed to the brink of depletion. Non-sustainable industrial practices are not only endangering the supply of the Earth's natural resources, but are also putting burden on life itself by bringing about pollution and climate change. A major role of earth science scholars is to examine the delicate balance between the Earth's resources and the growing demands of industrialization. Through research and development, earth scientists have the power to preserve the planet's different resource domains by providing expert opinion and information about the forces which make life possible on Earth. We would like to express our sincere gratitude to all in the Technical Program Committee who have reviewed the papers and developed a very interesting Conference Program as well as the invited and plenary speakers. This year, we received 78 papers and after rigorous review, 18 papers were accepted. The participants

  19. A backtranslation method based on codon usage strategy.

    PubMed Central

    Pesole, G; Attimonelli, M; Liuni, S

    1988-01-01

    This study describes a method for the backtranslation of an aminoacidic sequence, an extremely useful tool for various experimental approaches. It involves two computer programs CLUSTER and BACKTR written in Fortran 77 running on a VAX/VMS computer. CLUSTER generates a reliable codon usage table through a cluster analysis, based on a chi 2-like distance between the sequences. BACKTR produces backtranslated sequences according to different options when use is made of the codon usage table obtained in addition to selecting the least ambiguous potential oligonucleotide probes within an aminoacidic sequence. The method was tested by applying it to 158 yeast genes. PMID:3281142

  20. Gene classification using codon usage and support vector machines.

    PubMed

    Ma, Jianmin; Nguyen, Minh N; Rajapakse, Jagath C

    2009-01-01

    A novel approach for gene classification, which adopts codon usage bias as input feature vector for classification by support vector machines (SVM) is proposed. The DNA sequence is first converted to a 59-dimensional feature vector where each element corresponds to the relative synonymous usage frequency of a codon. As the input to the classifier is independent of sequence length and variance, our approach is useful when the sequences to be classified are of different lengths, a condition that homology-based methods tend to fail. The method is demonstrated by using 1,841 Human Leukocyte Antigen (HLA) sequences which are classified into two major classes: HLA-I and HLA-II; each major class is further subdivided into sub-groups of HLA-I and HLA-II molecules. Using codon usage frequencies, binary SVM achieved accuracy rate of 99.3% for HLA major class classification and multi-class SVM achieved accuracy rates of 99.73% and 98.38% for sub-class classification of HLA-I and HLA-II molecules, respectively. The results show that gene classification based on codon usage bias is consistent with the molecular structures and biological functions of HLA molecules. PMID:19179707

  1. Expression of a Chimeric Allergen with High Rare Codons Content in Codon Bias-Adjusted Escherichia coli: Escherichia coli BL21 (DE3)-Codon Plus RIL as an Efficient Host.

    PubMed

    Nouri, Hamid Reza; Karkhah, Ahmad; Varasteh, Abdolreza; Sankian, Mojtaba

    2016-07-01

    The expression of heterologous proteins in Escherichia coli (E. coli) is importantly affected by codon bias. Hence, the aim of the current study was to determine which codon bias-adjusted E. coli strain is sufficient for expression of a chimeric allergen coded by high rare codon content. To investigate the expression level, a chimeric protein of Chenopodium album (C. album) was used as an appropriate model. An expression construct was assembled and was transformed to four strains of codon bias-adjusted E. coli including origami, BL21 (DE3), BL21 (DE3)-codon plus RIL, and Rosetta. The level of expression and solubility of the chimeric allergen was analyzed by SDS-PAGE. In addition, the allergenicity of chimeric allergen was determined using immunoblotting. Our results showed that the chimeric allergen was expressed at high level in E. coli BL21 (DE3)-codon plus RIL and Rosetta. In detail, this recombinant allergen was isolated from soluble fraction in the codon bias-adjusted strains of E. coli BL21 (DE3)-codon plus RIL and Rosetta. Moreover, some lower molecular weight proteins were observed in Rosetta, which could be related to inappropriate expression or broken compartments of the chimeric allergen. The immunoblotting assay confirmed that the IgE-specific immune reactivity of our chimeric allergen expressed in BL21 (DE3)-codon plus RIL was significantly higher than the other strains. Our results showed that the expression of the chimeric allergen with high rare codons content in a codon bias-adjusted strain E. coli BL21 (DE3)-codon plus RIL improves the quality and solubility of the heterologous protein production. PMID:27040822

  2. Clustering of classical swine fever virus isolates by codon pair bias

    PubMed Central

    2011-01-01

    Background The genetic code consists of non-random usage of synonymous codons for the same amino acids, termed codon bias or codon usage. Codon juxtaposition is also non-random, referred to as codon context bias or codon pair bias. The codon and codon pair bias vary among different organisms, as well as with viruses. Reasons for these differences are not completely understood. For classical swine fever virus (CSFV), it was suggested that the synonymous codon usage does not significantly influence virulence, but the relationship between variations in codon pair usage and CSFV virulence is unknown. Virulence can be related to the fitness of a virus: Differences in codon pair usage influence genome translation efficiency, which may in turn relate to the fitness of a virus. Accordingly, the potential of the codon pair bias for clustering CSFV isolates into classes of different virulence was investigated. Results The complete genomic sequences encoding the viral polyprotein of 52 different CSFV isolates were analyzed. This included 49 sequences from the GenBank database (NCBI) and three newly sequenced genomes. The codon usage did not differ among isolates of different virulence or genotype. In contrast, a clustering of isolates based on their codon pair bias was observed, clearly discriminating highly virulent isolates and vaccine strains on one side from moderately virulent strains on the other side. However, phylogenetic trees based on the codon pair bias and on the primary nucleotide sequence resulted in a very similar genotype distribution. Conclusion Clustering of CSFV genomes based on their codon pair bias correlate with the genotype rather than with the virulence of the isolates. PMID:22126254

  3. Evolution of Synonymous Codon Usage in Neurospora tetrasperma and Neurospora discreta

    PubMed Central

    Whittle, C. A.; Sun, Y.; Johannesson, H.

    2011-01-01

    Neurospora comprises a primary model system for the study of fungal genetics and biology. In spite of this, little is known about genome evolution in Neurospora. For example, the evolution of synonymous codon usage is largely unknown in this genus. In the present investigation, we conducted a comprehensive analysis of synonymous codon usage and its relationship to gene expression and gene length (GL) in Neurospora tetrasperma and Neurospora discreta. For our analysis, we examined codon usage among 2,079 genes per organism and assessed gene expression using large-scale expressed sequenced tag (EST) data sets (279,323 and 453,559 ESTs for N. tetrasperma and N. discreta, respectively). Data on relative synonymous codon usage revealed 24 codons (and two putative codons) that are more frequently used in genes with high than with low expression and thus were defined as optimal codons. Although codon-usage bias was highly correlated with gene expression, it was independent of selectively neutral base composition (introns); thus demonstrating that translational selection drives synonymous codon usage in these genomes. We also report that GL (coding sequences [CDS]) was inversely associated with optimal codon usage at each gene expression level, with highly expressed short genes having the greatest frequency of optimal codons. Optimal codon frequency was moderately higher in N. tetrasperma than in N. discreta, which might be due to variation in selective pressures and/or mating systems. PMID:21402862

  4. The Stringency of Start Codon Selection in the Filamentous Fungus Neurospora crassa*

    PubMed Central

    Wei, Jiajie; Zhang, Ying; Ivanov, Ivaylo P.; Sachs, Matthew S.

    2013-01-01

    In eukaryotic cells initiation may occur from near-cognate codons that differ from AUG by a single nucleotide. The stringency of start codon selection impacts the efficiency of initiation at near-cognate codons and the efficiency of initiation at AUG codons in different contexts. We used a codon-optimized firefly luciferase reporter initiated with AUG or each of the nine near-cognate codons in preferred context to examine the stringency of start codon selection in the model filamentous fungus Neurospora crassa. In vivo results indicated that the hierarchy of initiation at start codons in N. crassa (AUG ≫ CUG > GUG > ACG > AUA ≈ UUG > AUU > AUC) is similar to that in human cells. Similar results were obtained by translating mRNAs in a homologous N. crassa in vitro translation system or in rabbit reticulocyte lysate. We next examined the efficiency of initiation at AUG, CUG, and UUG codons in different contexts in vitro. The preferred context was more important for efficient initiation from near-cognate codons than from AUG. These studies demonstrated that near-cognate codons are used for initiation in N. crassa. Such events could provide additional coding capacity or have regulatory functions. Analyses of the 5′-leader regions in the N. crassa transcriptome revealed examples of highly conserved near-cognate codons in preferred contexts that could extend the N termini of the predicted polypeptides. PMID:23396971

  5. Problem-Solving Test: The Effect of Synonymous Codons on Gene Expression

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2009-01-01

    Terms to be familiar with before you start to solve the test: the genetic code, codon, degenerate codons, protein synthesis, aminoacyl-tRNA, anticodon, antiparallel orientation, wobble, unambiguous codons, ribosomes, initiation, elongation and termination of translation, peptidyl transferase, translocation, degenerate oligonucleotides, green…

  6. Detecting molecular adaptation at individual codons in the glycoprotein gene of the geographically diversified infectious hematopoietic necrosis virus, a fish rhabdovirus.

    PubMed

    Padhi, Abinash; Verghese, Bindhu

    2008-03-01

    Salmonid fishes, the principal hosts of the infectious hematopoietic necrosis virus (IHNV), are a candidate species for aquaculture in many countries. IHNV causes an acute disease resulting in severe economic loss in salmonid fish farming. Previous phylogenetic analyses revealed the existence of multiple genogroups of this virus throughout the geographical range of its host. Here, we report the importance of natural selection in shaping the evolution of certain codons at the surface glycoprotein (G-protein) gene of this virus. Maximum likelihood (ML)-based codon substitution analyses revealed that approximately 2.8% of the codons for the entire G-protein are shown to have higher nonsynonymous substitution per nonsynonymous site (dn) than the synonymous substitutions per synonymous site (ds) (dn/ds=omega>4.335). Thus, the data suggest that positive selection (omega>1) is the major driving force in the evolution of certain codons. However, majority of these positively selected sites cannot be mapped to the regions of antigenic determinants of IHNV. Based on the reports of previous studies, epitopes with positively selected sites are immunodominant and viruses can escape from immune responses by producing antigenic variation at positively selected sites, therefore, vaccines directed against these neutralizing epitopes of IHNV that consist of no positively selected sites will be more effective. Some of the positively selected sites showed radical change in amino acids with respect to their charge and polarity; however, it is unclear how these changes affect the fitness of the virus. PMID:18178282

  7. Visualization of codon-dependent conformational rearrangements during translation termination

    PubMed Central

    He, Shan L.; Green, Rachel

    2010-01-01

    While the recognition of stop codons by class 1 release factors (RFs) on the ribosome takes place with extremely high fidelity, the molecular mechanisms behind this remarkable process are poorly understood. Here we performed structural probing experiments with Fe(II)-derivatized RFs to compare the conformation of cognate and near-cognate ribosome termination complexes. The structural differences that we document provide an unprecedented view of signal transduction on the ribosome that depends on authentic stop codon recognition. These events initiate with very close interactions between RF and the small subunit decoding center (DC), lead to increased interactions between the switch loop of the RF and specific regions of the subunit interface and end in the precise orientation of the RF for maximal catalytic activity in the large subunit peptidyl transferase center (PTC). PMID:20208546

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

    PubMed Central

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

    2016-01-01

    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. PMID:26927064

  9. The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons

    PubMed Central

    Simões, João; Bezerra, Ana R.; Moura, Gabriela R.; Araújo, Hugo; Gut, Ivo; Bayes, Mónica; Santos, Manuel A. S.

    2016-01-01

    The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT) strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans. PMID:27065968

  10. The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons.

    PubMed

    Simões, João; Bezerra, Ana R; Moura, Gabriela R; Araújo, Hugo; Gut, Ivo; Bayes, Mónica; Santos, Manuel A S

    2016-01-01

    The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT) strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans. PMID:27065968

  11. Decoding RAS isoform and codon-specific signalling

    PubMed Central

    Newlaczyl, Anna U.; Hood, Fiona E.; Coulson, Judy M.; Prior, Ian A.

    2014-01-01

    RAS proteins are key signalling hubs that are oncogenically mutated in 30% of all cancer cases. Three genes encode almost identical isoforms that are ubiquitously expressed, but are not functionally redundant. The network responses associated with each isoform and individual oncogenic mutations remain to be fully characterized. In the present article, we review recent data defining the differences between the RAS isoforms and their most commonly mutated codons and discuss the underlying mechanisms. PMID:25109951

  12. Codon Distribution in Error-Detecting Circular Codes

    PubMed Central

    Fimmel, Elena; Strüngmann, Lutz

    2016-01-01

    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. PMID:26999215

  13. Computational codon optimization of synthetic gene for protein expression

    PubMed Central

    2012-01-01

    Background The construction of customized nucleic acid sequences allows us to have greater flexibility in gene design for recombinant protein expression. Among the various parameters considered for such DNA sequence design, individual codon usage (ICU) has been implicated as one of the most crucial factors affecting mRNA translational efficiency. However, previous works have also reported the significant influence of codon pair usage, also known as codon context (CC), on the level of protein expression. Results In this study, we have developed novel computational procedures for evaluating the relative importance of optimizing ICU and CC for enhancing protein expression. By formulating appropriate mathematical expressions to quantify the ICU and CC fitness of a coding sequence, optimization procedures based on genetic algorithm were employed to maximize its ICU and/or CC fitness. Surprisingly, the in silico validation of the resultant optimized DNA sequences for Escherichia coli, Lactococcus lactis, Pichia pastoris and Saccharomyces cerevisiae suggests that CC is a more relevant design criterion than the commonly considered ICU. Conclusions The proposed CC optimization framework can complement and enhance the capabilities of current gene design tools, with potential applications to heterologous protein production and even vaccine development in synthetic biotechnology. PMID:23083100

  14. Novel small molecules potentiate premature termination codon readthrough by aminoglycosides.

    PubMed

    Baradaran-Heravi, Alireza; Balgi, Aruna D; Zimmerman, Carla; Choi, Kunho; Shidmoossavee, Fahimeh S; Tan, Jason S; Bergeaud, Célia; Krause, Alexandra; Flibotte, Stéphane; Shimizu, Yoko; Anderson, Hilary J; Mouly, Vincent; Jan, Eric; Pfeifer, Tom; Jaquith, James B; Roberge, Michel

    2016-08-19

    Nonsense mutations introduce premature termination codons and underlie 11% of genetic disease cases. High concentrations of aminoglycosides can restore gene function by eliciting premature termination codon readthrough but with low efficiency. Using a high-throughput screen, we identified compounds that potentiate readthrough by aminoglycosides at multiple nonsense alleles in yeast. Chemical optimization generated phthalimide derivative CDX5-1 with activity in human cells. Alone, CDX5-1 did not induce readthrough or increase TP53 mRNA levels in HDQ-P1 cancer cells with a homozygous TP53 nonsense mutation. However, in combination with aminoglycoside G418, it enhanced readthrough up to 180-fold over G418 alone. The combination also increased readthrough at all three nonsense codons in cancer cells with other TP53 nonsense mutations, as well as in cells from rare genetic disease patients with nonsense mutations in the CLN2, SMARCAL1 and DMD genes. These findings open up the possibility of treating patients across a spectrum of genetic diseases caused by nonsense mutations. PMID:27407112

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

    PubMed Central

    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

  16. Analysis of synonymous codon usage in porcine reproductive and respiratory syndrome virus.

    PubMed

    Liu, Yong-sheng; Zhou, Jian-hua; Chen, Hao-tai; Ma, Li-na; Ding, Yao-zhong; Wang, Meng; Zhang, Jie

    2010-08-01

    In this study, we calculated the relative synonymous codon usage (RSCU) values and codon usage bias (CUB) values to implement a comparative analysis of codon usage pattern of open reading frames (ORFs) which belong to the two main genotypes of porcine reproductive and respiratory syndrome virus (PRRSV). By analysis of synonymous codon usage values in each ORF of PRRSV, the optimal codons for most amino acids were all C or G-ended codons except GAU for Asp, CAU for His, UUU for Phe and CCU for Pro. The synonymous codon usage patterns in different ORFs of PRRSV were different and genetically conserved. Among them, ORF1a, ORF4, ORF5 and ORF7 could cluster these strains into the two main serotypes (EU and US). Due to mutational pressure, compositional constraint played an important role in shaping the synonymous codon usage pattern in different ORFs, and the synonymous codon usage diversity in ORFs was correlated with gene function. The degree of CUB for some particular amino acids under strong selection pressure probably served as a potential genetic marker for each ORF in PRRSV. However, gene length and translational selection in nature had no effect on the synonymous codon usage pattern in PRRSV. These conclusions could not only offer an insight into the synonymous codon usage pattern and differentiation of gene function, but also assist in understanding the discrepancy of evolution among ORFs in PRRSV. PMID:20438864

  17. Codon usage and protein sequence pattern dependency in different organisms: A Bioinformatics approach.

    PubMed

    Foroughmand-Araabi, Mohammad-Hadi; Goliaei, Bahram; Alishahi, Kasra; Sadeghi, Mehdi; Goliaei, Sama

    2015-04-01

    Although it is known that synonymous codons are not chosen randomly, the role of the codon usage in gene regulation is not clearly understood, yet. Researchers have investigated the relation between the codon usage and various properties, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Recently, a universal codon usage based mechanism for gene regulation is proposed. We studied the role of protein sequence patterns on the codons usage by related genes. Considering a subsequence of a protein that matches to a pattern or motif, we showed that, parts of the genes, which are translated to this subsequence, use specific ratios of synonymous codons. Also, we built a multinomial logistic regression statistical model for codon usage, which considers the effect of patterns on codon usage. This model justifies the observed codon usage preference better than the classic organism dependent codon usage. Our results showed that the codon usage plays a role in controlling protein levels, for genes that participate in a specific biological function. This is the first time that this phenomenon is reported. PMID:25409941

  18. Genome-wide analysis of synonymous codon usage in Huaiyangshan virus and other bunyaviruses.

    PubMed

    Luo, Xuelian; Liu, Qingzhen; Xiong, Yanwen; Ye, Changyun; Jin, Dong; Xu, Jianguo

    2015-12-01

    Huaiyangshan virus (HYSV) is a newly discovered bunyavirus, which is transmitted by ticks and causes hemorrhagic fever-like illness in human. The interplay of codon usage among viruses and their hosts is expected to affect viral survival, evasion from host's immune system and evolution. However, little is known about the codon usage in HYSV genome. In the present study, we analyzed synonymous codon usage in 120 available full-length HYSV sequences and performed a comparative analysis of synonymous codon usage patterns in HYSV and 42 other bunyaviruses. The relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C-ended. A comparative analysis of RSCU between HYSV and its hosts reflected that codon usage patterns of HYSV were mostly coincident with that of its hosts. Our data suggested that although mutational bias dominated codon usage, patterns of codon usage in HYSV were also under the influence of nature selection. Phylogenetic analysis based on RSCU values across different HYSV strains and 42 other bunyaviruses suggested that codon usage pattern in HYSV was the most similar with that of Uukuniemi virus among these bunyaviruses and that viruses belonged to Phlebovirus showed a diversity of codon usage patterns. PMID:26173646

  19. Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo

    PubMed Central

    Pechmann, Sebastian; Chartron, Justin W; Frydman, Judith

    2015-01-01

    The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35–40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome. PMID:25420103

  20. Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo.

    PubMed

    Pechmann, Sebastian; Chartron, Justin W; Frydman, Judith

    2014-12-01

    The genetic code allows most amino acids a choice of optimal and nonoptimal codons. We report that synonymous codon choice is tuned to promote interaction of nascent polypeptides with the signal recognition particle (SRP), which assists in protein translocation across membranes. Cotranslational recognition by the SRP in vivo is enhanced when mRNAs contain nonoptimal codon clusters 35-40 codons downstream of the SRP-binding site, the distance that spans the ribosomal polypeptide exit tunnel. A local translation slowdown upon ribosomal exit of SRP-binding elements in mRNAs containing these nonoptimal codon clusters is supported experimentally by ribosome profiling analyses in yeast. Modulation of local elongation rates through codon choice appears to kinetically enhance recognition by ribosome-associated factors. We propose that cotranslational regulation of nascent-chain fate may be a general constraint shaping codon usage in the genome. PMID:25420103

  1. Bioinformatics analysis of codon usage patterns and influencing factors in Penaeus monodon nudivirus.

    PubMed

    Tyagi, Anuj; Singh, Niraj K; Gurtler, Volker; Karunasagar, Indrani

    2016-02-01

    Penaeus monodon nudivirus (PmNV) is one of the most important and most commonly reported shrimp viruses. In the present study, codon usage of PmNV was studied in detail. Based on effective number of codons (ENC) values, strong to low codon usage bias was observed in PmNV genes. Nucleotide composition-ENC correlation analysis and the GC3 versus ENC relationship indicated that compositional constraint has a major effect on codon usage of PmNV. At the whole-genome level, relative synonymous codon usage (RSCU) analysis showed almost complete antagonism between the codon usage pattern of PmNV and its host P. monodon. However, codon adaptive index (CAI) values indicated that forces of selective/translational constraints have been able to overcome this antagonism in some genes. PMID:26586333

  2. Genetic analysis of L123 of the tRNA-mimicking eukaryote release factor eRF1, an amino acid residue critical for discrimination of stop codons

    PubMed Central

    Saito, Kazuki; Ito, Koichi

    2015-01-01

    In eukaryotes, the tRNA-mimicking polypeptide-chain release factor, eRF1, decodes stop codons on the ribosome in a complex with eRF3; this complex exhibits striking structural similarity to the tRNA–eEF1A–GTP complex. Although amino acid residues or motifs of eRF1 that are critical for stop codon discrimination have been identified, the details of the molecular mechanisms involved in the function of the ribosomal decoding site remain obscure. Here, we report analyses of the position-123 amino acid of eRF1 (L123 in Saccharomyces cerevisiae eRF1), a residue that is phylogenetically conserved among species with canonical and variant genetic codes. In vivo readthrough efficiency analysis and genetic growth complementation analysis of the residue-123 systematic mutants suggested that this amino acid functions in stop codon discrimination in a manner coupled with eRF3 binding, and distinctive from previously reported adjacent residues. Furthermore, aminoglycoside antibiotic sensitivity analysis and ribosomal docking modeling of eRF1 in a quasi-A/T state suggested a functional interaction between the side chain of L123 and ribosomal residues critical for codon recognition in the decoding site, as a molecular explanation for coupling with eRF3. Our results provide insights into the molecular mechanisms underlying stop codon discrimination by a tRNA-mimicking protein on the ribosome. PMID:25897120

  3. The Rare Codon AGA Is Involved in Regulation of Pyoluteorin Biosynthesis in Pseudomonas protegens Pf-5

    PubMed Central

    Yan, Qing; Philmus, Benjamin; Hesse, Cedar; Kohen, Max; Chang, Jeff H.; Loper, Joyce E.

    2016-01-01

    The soil bacterium Pseudomonas protegens Pf-5 can colonize root and seed surfaces of many plants, protecting them from infection by plant pathogenic fungi and oomycetes. The capacity to suppress disease is attributed to Pf-5's production of a large spectrum of antibiotics, which is controlled by complex regulatory circuits operating at the transcriptional and post-transcriptional levels. In this study, we analyzed the genomic sequence of Pf-5 for codon usage patterns and observed that the six rarest codons in the genome are present in all seven known antibiotic biosynthesis gene clusters. In particular, there is an abundance of rare codons in pltR, which encodes a member of the LysR transcriptional regulator family that controls the expression of pyoluteorin biosynthetic genes. To test the hypothesis that rare codons in pltR influence pyoluteorin production, we generated a derivative of Pf-5 in which 23 types of rare codons in pltR were substituted with synonymous preferred codons. The resultant mutant produced pyoluteorin at levels 15 times higher than that of the wild-type Pf-5. Accordingly, the promoter activity of the pyoluteorin biosynthetic gene pltL was 20 times higher in the codon-modified stain than in the wild-type. pltR has six AGA codons, which is the rarest codon in the Pf-5 genome. Substitution of all six AGA codons with preferred Arg codons resulted in a variant of pltR that conferred increased pyoluteorin production and pltL promoter activity. Furthermore, overexpression of tRNAUCUArg, the cognate tRNA for the AGA codon, significantly increased pyoluteorin production by Pf-5. A bias in codon usage has been linked to the regulation of many phenotypes in eukaryotes and prokaryotes but, to our knowledge, this is the first example of the role of a rare codon in the regulation of antibiotic production by a Gram-negative bacterium. PMID:27148187

  4. The Rare Codon AGA Is Involved in Regulation of Pyoluteorin Biosynthesis in Pseudomonas protegens Pf-5.

    PubMed

    Yan, Qing; Philmus, Benjamin; Hesse, Cedar; Kohen, Max; Chang, Jeff H; Loper, Joyce E

    2016-01-01

    The soil bacterium Pseudomonas protegens Pf-5 can colonize root and seed surfaces of many plants, protecting them from infection by plant pathogenic fungi and oomycetes. The capacity to suppress disease is attributed to Pf-5's production of a large spectrum of antibiotics, which is controlled by complex regulatory circuits operating at the transcriptional and post-transcriptional levels. In this study, we analyzed the genomic sequence of Pf-5 for codon usage patterns and observed that the six rarest codons in the genome are present in all seven known antibiotic biosynthesis gene clusters. In particular, there is an abundance of rare codons in pltR, which encodes a member of the LysR transcriptional regulator family that controls the expression of pyoluteorin biosynthetic genes. To test the hypothesis that rare codons in pltR influence pyoluteorin production, we generated a derivative of Pf-5 in which 23 types of rare codons in pltR were substituted with synonymous preferred codons. The resultant mutant produced pyoluteorin at levels 15 times higher than that of the wild-type Pf-5. Accordingly, the promoter activity of the pyoluteorin biosynthetic gene pltL was 20 times higher in the codon-modified stain than in the wild-type. pltR has six AGA codons, which is the rarest codon in the Pf-5 genome. Substitution of all six AGA codons with preferred Arg codons resulted in a variant of pltR that conferred increased pyoluteorin production and pltL promoter activity. Furthermore, overexpression of tRNA[Formula: see text], the cognate tRNA for the AGA codon, significantly increased pyoluteorin production by Pf-5. A bias in codon usage has been linked to the regulation of many phenotypes in eukaryotes and prokaryotes but, to our knowledge, this is the first example of the role of a rare codon in the regulation of antibiotic production by a Gram-negative bacterium. PMID:27148187

  5. Codon optimization and expression of irisin in Pichia pastoris GS115.

    PubMed

    Duan, Huikun; Wang, Haisong; Ma, Baicheng; Jiang, Pingzhe; Tu, Peipei; Ni, Zaizhong; Li, Xiaodan; Li, Miao; Ma, Xiaofeng; Wang, Bin; Wu, Ri; Li, Minggang

    2015-08-01

    Irisin is a novel hormone which is related to many metabolic diseases. In order to illuminate the function and therapeutic effect of irisin, gaining active irisin is necessary. In this work, a codon-optimized irisin gene was designed according to Pichia pastoris synonymous codon usage bias and cloned into the pPIC9K expression vector. Sequencing result indicating that the sequence of irisin was consistent with the modified irisin and the irisin was in frame with α-factor secretion signal ATG. The plasmid pPIC9K-irisin was transformed into GS115 P. pastoris cells through electroporation. The positive transformants were screened on MD medium and analyzed by PCR. Five recombinant GS115/pPIC9K-irisin strains were obtained, but only one strain expressed irisin successfully. SDS-PAGE and Western blot were used to assess the expression level and purity of irisin. The irisin was also simply purified and the effect of pH value, methanol concentration and induction time on the production of irisin was investigated. The results showed that the best conditions of irisin expression were as follows: pH 6.0, 2.0% methanol and induction for 96 h. This work laid the basis for further investigation into the therapeutic and pharmacological effects of irisin, as well as development of irisin-based therapy. PMID:25931394

  6. Expression, purification and identification of Pla a1 in a codon-optimized Platanus pollen allergen.

    PubMed

    Liu, Yun; Sun, Xiuzhen; Wang, Guizuo; Tao, Ailin; Wu, Yuanyuan; Li, Manxiang; Shi, Hongyang; Xie, Mei

    2015-08-01

    The present study aimed to express, purify and identify the major allergen gene, Pla a1, in Platanus pollen. According to previous studies, the major gene sequences of the Pla a1 allergen were obtained and codon optimization and synthesis of the genome were performed using DNAStar software. Following binding of the target gene fragment and the pET-44a vector, the JM109 cells were transfected to produce positive clones. The vectors were then transformed into Escherichia coli Rosetta cells to induce the expression of the target protein. The exogenous protein was purified using affinity chromatography and was identified by western blot analysis. Pla a1, the major allergen protein in Platanus pollen, was successfully isolated and this exogenous protein was purified using affinity chromatography. The present study was the first, to the best of our knowledge, to obtain expression of the allergen recombinant protein, Pla a1, fused with a Strep-TagII via codon optimization and provided the basis for the preparation of allergens with high purity, recombinant hypoallergenic allergens and allergen nucleic acid vaccines. PMID:25902014

  7. 3' UTR length and messenger ribonucleoprotein composition determine endocleavage efficiencies at termination codons.

    PubMed

    Boehm, Volker; Haberman, Nejc; Ottens, Franziska; Ule, Jernej; Gehring, Niels H

    2014-10-23

    Nonsense-mediated mRNA decay (NMD) degrades different classes of mRNAs, including transcripts with premature termination codons (PTCs). The NMD factor SMG6 initiates degradation of substrate mRNAs by endonucleolytic cleavage. Here, we aim to delineate the cascade of NMD-activating events that culminate in endocleavage. We report that long 3' UTRs elicit SMG6-mediated endonucleolytic degradation. The presence of an exon-junction complex (EJC) within the 3' UTR strongly stimulates endocleavage in a distance-independent manner. The interaction of SMG6 with EJCs is not required for endocleavage. Whereas the core NMD component UPF2 supports endonucleolytic decay of long 3' UTR mRNAs, it is mostly dispensable during EJC-stimulated endocleavage. Using high-throughput sequencing, we map endocleavage positions of different PTC-containing reporter mRNAs and an endogenous NMD substrate to regions directly at and downstream of the termination codon. These results reveal how messenger ribonucleoprotein (mRNP) parameters differentially influence SMG6-executed endonucleolysis and uncover central characteristics of this phenomenon associated with translation termination. PMID:25310981

  8. Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations.

    PubMed

    Matsumoto, Tomotaka; John, Anoop; Baeza-Centurion, Pablo; Li, Boyang; Akashi, Hiroshi

    2016-06-01

    A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees. PMID:26873577

  9. [Use of imaging methods in the current screening, diagnostics and treatment of breast cancer - Professional guidelines. 3rd Breast Cancer Consensus Meeting].

    PubMed

    Forrai, Gábor; Ambrózay, Éva; Bidlek, Mária; Borbély, Katalin; Kovács, Eszter; Lengyel, Zsolt; Ormándi, Katalin; Péntek, Zoltán; Riedl, Erika; Sebõ, Éva; Szabó, Éva

    2016-09-01

    Breast radiologists and nuclear medical specialists have refreshed their previous statement text during the 3rd Hungarian Breast Cancer Consensus Meeting. They suggest taking into consideration this actual protocol for the screening, diagnostics and treatment of breast tumors, from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the follow-up. Suggestions for improvement of the Hungarian current practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The statement text has been cross-checked with the related medical disciplines. PMID:27579719

  10. [Damage-loss relationships and integrated control of 3rd instar larvae of Actias selene nigpoana Felder in planting area of Cornus officinalis Sieb. et Zucc].

    PubMed

    Chen, S; Wang, C; Zhang, Q; Cheng, X

    1997-08-01

    In the present paper, the damage-loss model of Actias selene ningpoana to Cornus officinalis was tested and the results indicated that the yield loss rates obeyed the equation Y = 100 - EXP(4.6042 - 0.0315X). The economic threshold of the 2hd and 3rd instar larvae of A. selene nigpoana was then determined as 22 and 8 insects per tree respecitively. Suggestions for integrated control have been made based on the research of activities of A. selene ningpoana in the forest. PMID:11038910

  11. Nucleotides Flanking the Start Codon in hsp70 mRNAs with Very Short 5’-UTRs Greatly Affect Gene Expression in Haloarchaea

    PubMed Central

    Chen, Wenchao; Yang, Guopeng; He, Yue; Zhang, Shaoming; Chen, Haiyan; Shen, Ping; Chen, Xiangdong; Huang, Yu-Ping

    2015-01-01

    Leaderless translation is prevalent in haloarchaea, with many of these leaderless transcripts possessing short 5’-untranslated regions (UTRs) less than 10 nucleotides. Whereas, little is known about the function of this very short 5’-UTR. Our previous studies determined that just four nucleotides preceded the start codon of hsp70 mRNA in Natrinema sp. J7, with residues -3A and +4G, relative to the A of the ATG start codon, acting as the preferred bases around the start codon of all known haloarchaeal hsp70 genes. Here, we examined the effects of nucleotides flanking the start codon on gene expression. The results revealed that shortening and deletion of the short 5’-UTR enhanced transcript levels; however, it led to significant reductions in overall translational efficiency. AUG was efficiently used as start codons, in both the presence and absence of short 5’-UTRs. GUG also could initiate translation, even though it was so inefficient that it would not be detected without considerably elevated transcript. Nucleotide substitutions at position -4 to +6 were shown to affect gene expression by transcript and/or translational levels. Notably, -3A and A/U nucleotides at position +4~+6 were more optimal for gene expression. Nucleotide transversions of -3A to -3C and +4G to +4T with hsp70 promoter from either Haloferax volcanii DS70 or Halobacterium salinarum NRC-1 showed the same effects on gene expression as that of Natrinema sp. J7. Taken together, our results suggest that the nucleotides flanking the start codon in hsp70 mRNAs with very short 5’-UTRs play an important role in haloarchaeal gene expression. PMID:26379277

  12. Re-exploration of the Codon Context Effect on Amber Codon-Guided Incorporation of Noncanonical Amino Acids in Escherichia coli by the Blue-White Screening Assay.

    PubMed

    Xu, Huan; Wang, Yan; Lu, Jiaqi; Zhang, Bo; Zhang, Ziwei; Si, Longlong; Wu, Ling; Yao, Tianzhuo; Zhang, Chuanling; Xiao, Sulong; Zhang, Lihe; Xia, Qing; Zhou, Demin

    2016-07-01

    The effect of codon context on amber codon-guided incorporation of noncanonical amino acids (NAAs) has been previously examined by antibiotic selection. Here, we re-explored this effect by screening a library in which three nucleotides upstream and downstream of the amber codon were randomised, and inserted within the lacZ-α gene. Thousands of clones were obtained and distinguished by the depth of blue colour upon exposure to X-gal. Large-scale sequencing revealed remarkable preferences in nucleotides downstream of the amber codon, and moderate preferences for upstream nucleotides. Nucleotide preference was quantified by a dual-luciferase assay, which verified that the optimum context for NAA incorporation, AATTAGACT, was applicable to different proteins. Our work provides a general guide for engineering amber codons into genes of interest in bacteria. PMID:27028123

  13. Efficacy of a 3rd generation high-throughput sequencing platform for analyses of 16S rRNA genes from environmental samples.

    PubMed

    Mosher, Jennifer J; Bernberg, Erin L; Shevchenko, Olga; Kan, Jinjun; Kaplan, Louis A

    2013-11-01

    Longer sequences of the bacterial 16S rRNA gene could provide greater phylogenetic and taxonomic resolutions and advance knowledge of population dynamics within complex natural communities. We assessed the accuracy of a Pacific Biosciences (PacBio) single molecule, real time (SMRT) sequencing based on DNA polymerization, a promising 3rd generation high-throughput technique, and compared this to the 2nd generation Roche 454 pyrosequencing platform. Amplicons of the 16S rRNA gene from a known isolate, Shewanella oneidensis MR1, and environmental samples from two streambed habitats, rocks and sediments, and a riparian zone soil, were analyzed. On the PacBio we analyzed ~500 bp amplicons that covered the V1-V3 regions and the full 1500 bp amplicons of the V1-V9 regions. On the Roche 454 we analyzed the ~500 bp amplicons. Error rates associated with the isolate were lowest with the Roche 454 method (2%), increased by more than 2-fold for the 500 bp amplicons with the PacBio SMRT chip (4-5%), and by more than 8-fold for the full gene with the PacBio SMRT chip (17-18%). Higher error rates with the PacBio SMRT chip artificially inflated estimates of richness and lowered estimates of coverage for environmental samples. The 3rd generation sequencing technology we evaluated does not provide greater phylogenetic and taxonomic resolutions for studies of microbial ecology. PMID:23999276

  14. Comprehensive Analysis of Stop Codon Usage in Bacteria and Its Correlation with Release Factor Abundance*

    PubMed Central

    Korkmaz, Gürkan; Holm, Mikael; Wiens, Tobias; Sanyal, Suparna

    2014-01-01

    We present a comprehensive analysis of stop codon usage in bacteria by analyzing over eight million coding sequences of 4684 bacterial sequences. Using a newly developed program called “stop codon counter,” the frequencies of the three classical stop codons TAA, TAG, and TGA were analyzed, and a publicly available stop codon database was built. Our analysis shows that with increasing genomic GC content the frequency of the TAA codon decreases and that of the TGA codon increases in a reciprocal manner. Interestingly, the release factor 1-specific codon TAG maintains a more or less uniform frequency (∼20%) irrespective of the GC content. The low abundance of TAG is also valid with respect to expression level of the genes ending with different stop codons. In contrast, the highly expressed genes predominantly end with TAA, ensuring termination with either of the two release factors. Using three model bacteria with different stop codon usage (Escherichia coli, Mycobacterium smegmatis, and Bacillus subtilis), we show that the frequency of TAG and TGA codons correlates well with the relative steady state amount of mRNA and protein for release factors RF1 and RF2 during exponential growth. Furthermore, using available microarray data for gene expression, we show that in both fast growing and contrasting biofilm formation conditions, the relative level of RF1 is nicely correlated with the expression level of the genes ending with TAG. PMID:25217634

  15. Association of HER2 codon 655 polymorphism with ovarian cancer.

    PubMed

    Watrowski, Rafał; Castillo-Tong, Dan Cacsire; Schuster, Eva; Fischer, Michael B; Speiser, Paul; Zeillinger, Robert

    2016-06-01

    The role of the human epidermal growth factor receptor 2 (HER2) codon 655 (Ile655Val) polymorphism in ovarian cancer is not fully understood. Two studies indicated a possible association between the Val allele and elevated risk or reduced prognosis of ovarian cancer. We investigated the HER2 codon 655 (rs1136201) polymorphism in 242 Austrian women-142 ovarian cancer patients and 100 healthy controls-by polymerase chain reaction and pyrosequencing. Associations between Ile655Val polymorphism and clinicopathological variables (e.g., age, FIGO stage, grading, serous vs. non-serous histology) were evaluated. The genotype distributions in ovarian cancer patients and controls were: AA; 66.2 %, AG; 25.35 %, GG; 8.45 %, and AA; 63 %, AG; 34 %, GG; 3.7 %, respectively (OR 1.15, CI 95 % 0.67-1.96). We observed a non-significant trend toward elevated cancer risk in Val/Val genotype (OR 2.98, CI 95 % 0.82-10.87, p = 0.10). Of note, 11 out of 12 Val/Val homozygotes were postmenopausal. The link between the Val/Val homozygosity and age over 50 years at diagnosis (OR 0.15, CI 95 % 0.02-1.2) was barely significant (p = 0.056). Summarizing, our data indicated a non-significant trend toward increased ovarian cancer risk in the Val/Val homozygosity, especially in women aged above 50 years. Further large-cohort studies focusing on the role of the HER2 codon 655 Val allele are needed. PMID:26666819

  16. Synthetic approach to stop-codon scanning mutagenesis.

    PubMed

    Nie, Lihua; Lavinder, Jason J; Sarkar, Mohosin; Stephany, Kimberly; Magliery, Thomas J

    2011-04-27

    A general combinatorial mutagenesis strategy using common dimethoxytrityl-protected mononucleotide phosphoramidites and a single orthogonally protected trinucleotide phosphoramidite (Fmoc-TAG; Fmoc = 9-fluorenylmethoxycarbonyl) was developed to scan a gene with the TAG amber stop codon with complete synthetic control. In combination with stop-codon suppressors that insert natural (e.g., alanine) or unnatural (e.g., p-benzoylphenylalanine, Bpa) amino acids, a single DNA library can be used to incorporate different amino acids for diverse purposes. Here, we scanned TAG codons through part of the gene for a model four-helix bundle protein, Rop, which regulates the copy number of ColE1 plasmids. Alanine was incorporated into Rop for mapping its binding site using an in vivo activity screen, and subtle but important differences from in vitro gel-shift studies of Rop function are evident. As a test, Bpa was incorporated using a Phe14 amber mutant isolated from the scanning library. Surprisingly, Phe14Bpa-Rop is weakly active, despite the critical role of Phe14 in Rop activity. Bpa is a photoaffinity label unnatural amino acid that can form covalent bonds with adjacent molecules upon UV irradiation. Irradiation of Phe14Bpa-Rop, which is a dimer in solution like wild-type Rop, results in covalent dimers, trimers, and tetramers. This suggests that Phe14Bpa-Rop weakly associates as a tetramer in solution and highlights the use of Bpa cross-linking as a means of trapping weak and transient interactions. PMID:21452871

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

    PubMed

    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. PMID:26498580

  18. Saving the 2nd Molar from the 3rd Is it Really the Guilt of the Tilt?

    PubMed Central

    Yadav, Pankaj; Nawal, Ruchika Roongta; Talwar, Sangeeta; Verma, Mahesh

    2016-01-01

    Introduction Clinicians often relate the distal caries in second molars to angulated third molars, which if left undetected can lead to gross decay that may further require removal of the tooth. Due to this fact, many third molars are advised for prophylactic removal to prevent decay in the second molar. But this approach would only be justified when the incidence of decay/loss of second molar due to third molar are reasonably high. We sought to determine incidence of caries experience and also sequel extraction in second molars associated with the third molars. Aim The study was conducted to answer the basic question that whether the incidence of caries and subsequent extraction of second molar due to angulated third molars is high enough to justify the prophylactic removal of third molar or not. Materials and Methods This study was conducted on radiographic records of 1187 patients. The effect of tilted third molar on the second molar was measured in relation with three parameters namely level & position of third molar with respect to second molar and the distribution among arches. Results The results indicated that out of total number of teeth examined only 5.4% of maxillary and 9.6% of mandibular second molars were affected by tilted third molars. Further, only 2.2% of mandibular and 2.9% of maxillary second molars were indicated for extraction. The data was statistically insignificant. Conclusion It was concluded that distal caries in second molars is not very common. It may be present in some cases of third molar impactions and prophylactic removal of these impacted teeth may not be considered appropriate. PMID:27437353

  19. Synonymous Codon Usage Bias in Plant Mitochondrial Genes Is Associated with Intron Number and Mirrors Species Evolution

    PubMed Central

    Zhao, Mingming; Yin, Xunhao; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is a common event that a non-uniform usage of codons often occurs in nearly all organisms. We previously found that SCUB is correlated with both intron number and exon position in the plant nuclear genome but not in the plastid genome; SCUB in both nuclear and plastid genome can mirror the evolutionary specialization. However, how about the rules in the mitochondrial genome has not been addressed. Here, we present an analysis of SCUB in the mitochondrial genome, based on 24 plant species ranging from algae to land plants. The frequencies of NNA and NNT (A- and T-ending codons) are higher than those of NNG and NNC, with the strongest preference in bryophytes and the weakest in land plants, suggesting an association between SCUB and plant evolution. The preference for NNA and NNT is more evident in genes harboring a greater number of introns in land plants, but the bias to NNA and NNT exhibits even among exons. The pattern of SCUB in the mitochondrial genome differs in some respects to that present in both the nuclear and plastid genomes. PMID:26110418

  20. Synonymous Codon Usage Bias in the Plastid Genome is Unrelated to Gene Structure and Shows Evolutionary Heterogeneity

    PubMed Central

    Qi, Yueying; Xu, Wenjing; Xing, Tian; Zhao, Mingming; Li, Nana; Yan, Li; Xia, Guangmin; Wang, Mengcheng

    2015-01-01

    Synonymous codon usage bias (SCUB) is the nonuniform usage of codons, occurring often in nearly all organisms. Our previous study found that SCUB is correlated with intron number, is unequal among exons in the plant nuclear genome, and mirrors evolutionary specialization. However, whether this rule exists in the plastid genome has not been addressed. Here, we present an analysis of SCUB in the plastid genomes of 25 species from lower to higher plants (algae, bryophytes, pteridophytes, gymnosperms, and spermatophytes). We found NNA and NNT (A- and T-ending codons) are preferential in the plastid genomes of all plants. Interestingly, this preference is heterogeneous among taxonomies of plants, with the strongest preference in bryophytes and the weakest in pteridophytes, suggesting an association between SCUB and plant evolution. In addition, SCUB frequencies are consistent among genes with varied introns and among exons, indicating that the bias of NNA and NNT is unrelated to either intron number or exon position. Further, SCUB is associated with DNA methylation–induced conversion of cytosine to thymine in the vascular plants but not in algae or bryophytes. These data demonstrate that these SCUB profiles in the plastid genome are distinctly different compared with the nuclear genome. PMID:25922569

  1. Translational readthrough potential of natural termination codons in eucaryotes – The impact of RNA sequence

    PubMed Central

    Dabrowski, Maciej; Bukowy-Bieryllo, Zuzanna; Zietkiewicz, Ewa

    2015-01-01

    Termination of protein synthesis is not 100% efficient. A number of natural mechanisms that suppress translation termination exist. One of them is STOP codon readthrough, the process that enables the ribosome to pass through the termination codon in mRNA and continue translation to the next STOP codon in the same reading frame. The efficiency of translational readthrough depends on a variety of factors, including the identity of the termination codon, the surrounding mRNA sequence context, and the presence of stimulating compounds. Understanding the interplay between these factors provides the necessary background for the efficient application of the STOP codon suppression approach in the therapy of diseases caused by the presence of premature termination codons. PMID:26176195

  2. Codon usage determines the mutational robustness, evolutionary capacity and virulence of an RNA virus

    PubMed Central

    Lauring, Adam S.; Acevedo, Ashley; Cooper, Samantha B.; Andino, Raul

    2012-01-01

    Summary RNA viruses exist as dynamic and diverse populations shaped by constant mutation and selection. Yet little is known about how the mutant spectrum contributes to virus evolvability and pathogenesis. Because several codon choices are available for a given amino acid, a central question concerns whether viral sequences have evolved to optimize not only the protein coding consensus, but also the DNA/RNA sequences accessible through mutation. Here we directly test this hypothesis by comparing wild type poliovirus to synthetic viruses carrying reengineered capsid sequences with hundreds of synonymous mutations. Strikingly, such rewiring of the population's mutant network reduced its robustness and attenuated the virus in an animal model of infection. We conclude that the position of a virus in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenicity. This organizing principle for RNA virus populations confers tolerance to mutations and facilitates replication and spread within the dynamic host environment. PMID:23159052

  3. Translation initiation in Drosophila melanogaster is reduced by mutations upstream of the AUG initiator codon

    SciTech Connect

    Feng, Yue; Gunter, L.E.; Organ, E.L.; Cavener, D.R. )

    1991-04-01

    The importance to in vivo translation of sequences immediately upstream of the Drosophila alcohol dehydrogenase (Adh) start codon was examined at two developmental stages. Mutations were introduced into the Adh gene in vitro, and the mutant gene was inserted into the genome via germ line transformation. An A-to-T substitution at the [minus]3 position did not affect relative translation of ADH at the adult stage. A second mutant gene, containing five mutations in the region [minus]1 to [minus]9, was designed to completely block translation initiation. However, transformant lines bearing these mutations still exhibit detectable ADH, albeit at substantially reduced levels. The average fold reduction at the second-instar larval stage was 5.9, while at the adult stage a 12.5-fold reduction was observed.

  4. Analysis of phylogeny and codon usage bias and relationship of GC content, amino acid composition with expression of the structural nif genes.

    PubMed

    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. PMID:26309237

  5. Selection at the amino acid level can influence synonymous codon usage: implications for the study of codon adaptation in plastid genes.

    PubMed Central

    Morton, B R

    2001-01-01

    A previously employed method that uses the composition of noncoding DNA as the basis of a test for selection between synonymous codons in plastid genes is reevaluated. The test requires the assumption that in the absence of selective differences between synonymous codons the composition of silent sites in coding sequences will match the composition of noncoding sites. It is demonstrated here that this assumption is not necessarily true and, more generally, that using compositional properties to draw inferences about selection on silent changes in coding sequences is much more problematic than commonly assumed. This is so because selection on nonsynonymous changes can influence the composition of synonymous sites (i.e., codon usage) in a complex manner, meaning that the composition biases of different silent sites, including neutral noncoding DNA, are not comparable. These findings also draw into question the commonly utilized method of investigating how selection to increase translation accuracy influences codon usage. The work then focuses on implications for studies that assess codon adaptation, which is selection on codon usage to enhance translation rate, in plastid genes. A new test that does not require the use of noncoding DNA is proposed and applied. The results of this test suggest that far fewer plastid genes display codon adaptation than previously thought. PMID:11560910

  6. Interspecific adaptation by binary choice at de novo polyomavirus T antigen site through accelerated codon-constrained Val-Ala toggling within an intrinsically disordered region

    PubMed Central

    Lauber, Chris; Kazem, Siamaque; Kravchenko, Alexander A.; Feltkamp, Mariet C.W.; Gorbalenya, Alexander E.

    2015-01-01

    It is common knowledge that conserved residues evolve slowly. We challenge generality of this central tenet of molecular biology by describing the fast evolution of a conserved nucleotide position that is located in the overlap of two open reading frames (ORFs) of polyomaviruses. The de novo ORF is expressed through either the ALTO protein or the Middle T antigen (MT/ALTO), while the ancestral ORF encodes the N-terminal domain of helicase-containing Large T (LT) antigen. In the latter domain the conserved Cys codon of the LXCXE pRB-binding motif constrains codon evolution in the overlapping MT/ALTO ORF to a binary choice between Val and Ala codons, termed here as codon-constrained Val-Ala (COCO-VA) toggling. We found the rate of COCO-VA toggling to approach the speciation rate and to be significantly accelerated compared to the baseline rate of chance substitution in a large monophyletic lineage including all viruses encoding MT/ALTO and three others. Importantly, the COCO-VA site is located in a short linear motif (SLiM) of an intrinsically disordered region, a typical characteristic of adaptive responders. These findings provide evidence that the COCO-VA toggling is under positive selection in many polyomaviruses, implying its critical role in interspecific adaptation, which is unprecedented for conserved residues. PMID:25904630

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

    SciTech Connect

    Petraroli, R.; Pocchiari, M.

    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.

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

    PubMed

    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. PMID:27197221

  9. Translationally optimal codons associate with aggregation-prone sites in proteins.

    PubMed

    Lee, Yaelim; Zhou, Tong; Tartaglia, Gian Gaetano; Vendruscolo, Michele; Wilke, Claus O

    2010-12-01

    We analyze the relationship between codon usage bias and residue aggregation propensity in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse, as well as the archaeon Halobacterium species NRC-1. Using the Mantel-Haenszel procedure, we find that translationally optimal codons associate with aggregation-prone residues. Our results are qualitatively and quantitatively similar to those of an earlier study where we found an association between translationally optimal codons and buried residues. We also combine the aggregation-propensity data with solvent-accessibility data. Although the resulting data set is small, and hence statistical power low, results indicate that the association between optimal codons and aggregation-prone residues exists both at buried and at exposed sites. By comparing codon usage at different combinations of sites (exposed, aggregation-prone sites versus buried, non-aggregation-prone sites; buried, aggregation-prone sites versus exposed, non-aggregation-prone sites), we find that aggregation propensity and solvent accessibility seem to have independent effects of (on average) comparable magnitude on codon usage. Finally, in fly, we assess whether optimal codons associate with sites at which amino acid substitutions lead to an increase in aggregation propensity, and find only a very weak effect. These results suggest that optimal codons may be required to reduce the frequency of translation errors at aggregation-prone sites that coincide with certain functional sites, such as protein-protein interfaces. Alternatively, optimal codons may be required for rapid translation of aggregation-prone regions. PMID:21046618

  10. Codon optimality is a major determinant of mRNA stability

    PubMed Central

    Presnyak, Vladimir; Alhusaini, Najwa; Chen, Ying-Hsin; Martin, Sophie; Morris, Nathan; Kline, Nicholas; Olson, Sara; Weinberg, David; Baker, Kristian E.; Graveley, Brenton R.; Coller, Jeff

    2015-01-01

    Messenger RNA degradation represents a critical regulated step in gene expression. While the major pathways in turnover have been identified, accounting for disparate half-lives has been elusive. We show that codon optimality is one feature that contributes greatly to mRNA stability. Genome-wide RNA decay analysis revealed that stable mRNAs are enriched in codons designated optimal, whereas unstable mRNAs contain predominately non-optimal codons. Substitution of optimal codons with synonymous, non-optimal codons results in dramatic mRNA destabilization, while the converse substitution significantly increases stability. Further, we demonstrate that codon optimality impacts ribosome translocation, connecting the processes of translation elongation and decay through codon optimality. Finally, we show that optimal codon content accounts for the similar stabilities observed in mRNAs encoding proteins with coordinated physiological function. This work demonstrates that codon optimization exists as an mechanism to finely tune levels of mRNAs, and ultimately, proteins. PMID:25768907

  11. Analysis of synonymous codon usage in spike protein gene of infectious bronchitis virus.

    PubMed

    Makhija, Aditi; Kumar, Sachin

    2015-12-01

    Infectious bronchitis virus (IBV) is responsible for causing respiratory, renal, and urogenital diseases in poultry. IBV infection in poultry leads to high mortality rates in affected flocks and to severe economic losses due to a drop in egg production and a reduced gain in live weight of the broiler birds. IBV-encoded spike protein (S) is the major protective immunogen for the host. Although the functions of the S protein have been well studied, the factors shaping synonymous codon usage bias and nucleotide composition in the S gene have not been reported yet. In the present study, we analyzed the relative synonymous codon usage and effective number of codons (Nc) using the 53 IBV S genes. The major trend in codon usage variation was studied using correspondence analysis. The plot of Nc values against GC3 as well as the correlation between base composition and codon usage bias suggest that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in the S gene. Interestingly, no association of aromaticity, degree of hydrophobicity, and aliphatic index was observed with the codon usage variation in IBV S genes. The study represents a comprehensive analysis of IBV S gene codon usage patterns and provides a basic understanding of the codon usage bias. PMID:26452019

  12. Prevalent Accumulation of Non-Optimal Codons through Somatic Mutations in Human Cancers

    PubMed Central

    Wu, Xudong; Li, Guohui

    2016-01-01

    Cancer is characterized by uncontrolled cell growth, and the cause of different cancers is generally attributed to checkpoint dysregulation of cell proliferation and apoptosis. Recent studies have shown that non-optimal codons were preferentially adopted by genes to generate cell cycle-dependent oscillations in protein levels. This raises the intriguing question of how dynamic changes of codon usage modulate the cancer genome to cope with a non-controlled proliferative cell cycle. In this study, we comprehensively analyzed the somatic mutations of codons in human cancers, and found that non-optimal codons tended to be accumulated through both synonymous and non-synonymous mutations compared with other types of genomic substitution. We further demonstrated that non-optimal codons were prevalently accumulated across different types of cancers, amino acids, and chromosomes, and genes with accumulation of non-optimal codons tended to be involved in protein interaction/signaling networks and encoded important enzymes in metabolic networks that played roles in cancer-related pathways. This study provides insights into the dynamics of codons in the cancer genome and demonstrates that accumulation of non-optimal codons may be an adaptive strategy for cancerous cells to win the competition with normal cells. This deeper interpretation of the patterns and the functional characterization of somatic mutations of codons will help to broaden the current understanding of the molecular basis of cancers. PMID:27513638

  13. Analysis of codon usage pattern evolution in avian rotaviruses and their preferred host.

    PubMed

    Kattoor, Jobin Jose; Malik, Yashpal Singh; Sasidharan, Aravind; Rajan, Vishnuraj Mangalathu; Dhama, Kuldeep; Ghosh, Souvik; Bányai, Krisztián; Kobayashi, Nobumichi; Singh, Raj Kumar

    2015-08-01

    Rotavirus infection is a worldwide problem, with occurrence of highly divergent viruses classified in 8 species (A-H). We report here the evolution assessment of codon usage patterns in virus-host system in avian rotavirus (AvRV) of species RVA, RVD, RVF and RVG (preferentially affecting birds). The nucleotide contents, codon usage bias (CUB), relative synonymous codon usage (RSCU), and effective number of codons (ENCs) values were investigated targeting overexpressing major inner capsid viral protein (VP6) of these AvRV species. The results confirm that the evolutionary characteristics influences the rotavirus (RV) genetic diversity and impact of host's natural selection on the AvRVs codons. Synonymous codon usage patterns were evaluated following multivariate statistical procedures on all available AvRV coding gene sequences. RSCU trees accommodated all AvRV species and preferred host sequences in one topology confirming greater imminence of AvRVs with the host chicken cell genes. Similarly, the codon adaptation index (CAI) results also displayed a higher adaptation of AvRVs to its chicken host. The codon preference analysis of RVs revealed that VP6 gene express more proficiently in the yeast system, whereas, codon optimization might be required for the effectual expression in Escherichia coli and Homo sapiens. The findings provide basic evidence on the dynamics of AvRV evolution and its host adaptation, which could be exploited for additional research on avian species in future. PMID:26086995

  14. Deuterium beam acceleration with 3rd harmonic ion cyclotron resonance heating in Joint European Torus: Sawtooth stabilization and Alfvén eigenmodes

    NASA Astrophysics Data System (ADS)

    Gassner, T.; Schoepf, K.; Sharapov, S. E.; Kiptily, V. G.; Pinches, S. D.; Hellesen, C.; Eriksson, J.; JET-EFDA contributors

    2012-03-01

    Experiments on accelerating NBI-produced deuterium (D) beam ions from their injection energy of ˜110 keV up to the MeV energy range with 3rd harmonic ion cyclotron resonance heating were performed on the Joint European Torus [P. H. Rebut and B. E. Keen, Fusion Technol. 11, 13 (1987)]. A renewed set of nuclear diagnostics was used for analysing fast D ions during sawtooth stabilization, monster sawtooth crashes, and during excitation of Alfvén eigenmodes (AEs) residing inside the q = 1 radius. The measurements and modeling of the fast ions with the nonlinear HAGIS code [S. D. Pinches et al., Comput. Phys. Commun. 111, 133 (1998)] show that monster sawtooth crashes are strongly facilitated by the AE-induced re-distribution of the fast D ions from inside the q = 1 radius to the plasma edge.

  15. [Pathological diagnosis, work-up and reporting of breast cancer. Recommendations of the 3rd Hungarian Consensus Conference on Breast Cancer].

    PubMed

    Cserni, Gábor; Kulka, Janina; Francz, Monika; Járay, Balázs; Kálmán, Endre; Kovács, Ilona; Krenács, Tibor; Udvarhelyi, Nóra; Vass, László

    2016-09-01

    There have been relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2010 recommendations made during the 2nd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 3rd Hungarian Consensus Conference on Breast Cancer. The recommendations cover non-operative and intraoperative diagnostics, the work-up of operative specimens, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future. PMID:27579721

  16. From challenges to solutions. European Bioanalysis Forum 3rd Annual Open Symposium, Hesperia Towers, Barcelona, Spain, 1-3 December 2010.

    PubMed

    Abbott, Richard W; Gordon, Ben; van Amsterdam, Peter; Lausecker, Berthold; Brudny-Kloeppel, Margarete; Smeraglia, John; Romero, Fernando; Globig, Susanne; Golob, Michaela; Knutsson, Magnus; Herling, Christian; Vieser, Eva; Timmerman, Philip

    2011-04-01

    The European Bioanalysis Forum is a bioanalytical nonprofit organization comprised of European pharmaceutical companies (27 members to date) and currently expanding to include CROs as well. The European Bioanalysis Forum provides a broad European bioanalytical network for the discussion of scientific, technological and regulatory topics of bioanalytical interest. The 3rd Annual Open Symposium was again much anticipated after the two previous successful meetings. The symposium included sessions on thinking outside the 'commodity' box, bioanalytical challenges with blood, global harmonization, assay platforms, dried blood spots, immunogenicity, matrix effects, anomalous results, biomarkers and two plenary technology sessions hosted by the Platinum sponsors. Experts and key opinion leaders were invited as guest speakers. A total of 424 delegates registered from 113 companies representing a large percentage of the European bioanalytical community. In addition to 48 oral presentations, 88 posters were presented and there was a vendor exposition of 40 companies. PMID:21510756

  17. [3rd generation's TKI in lung cancer non-small cell EGFR-mutated having acquired a secondary T790M resistance].

    PubMed

    Brosseau, Solenn; Viala, Marie; Varga, Andréa; Planchard, David; Besse, Benjamin; Soria, Jean-Charles

    2015-09-01

    Activating EGFR mutations discovery and efficacy of 1st generation tyrosine kinase inhibitors (TKI), such as erlotinib or gefitinib, inaugurated the beginning of personalized medicine in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). However, all patients showed a tumor progression of 10 to 16 months after the onset of TKI therapy related to molecular resistance mechanisms as T790M mutation. Till now, patients suffering from EGFR-mutated NSCLC with acquired resistance have conventional treatment options. Two new 3rd generations' TKI, AZD9291 and rociletinib, are currently being studied in phases 1-3 studies. Preliminary results show relevant therapeutic properties in patients with T790M mutated-EGFR NSCLC. This review aims to highlight these new molecules, their effectiveness and their clinical toxicities in the treatment of advanced stages of NSCLC expressing the T790M mutation. PMID:26235419

  18. Reflections: Surgical Education-the Times they are a-Changin': Lessons Learned from the 3rd MAYMET-ESO Joint Meeting.

    PubMed

    Tarkowski, Radoslaw; Vetto, John T

    2015-09-01

    Technical skills are not sufficient for successful surgical care. Non-technical skills such as team work, decision-making in cancer treatment, communication with the patient, ethical challenges, situation awareness, and communication in the operating room are mandatory for favorable outcomes. Although formally taught in other high-demand disciplines, such skills were traditionally rarely discussed in surgical oncology. The 3rd MAYMET-ESO Joint Meeting "Professionalism for Breast Surgeons" held in Istanbul, Turkey, 5 October 2013 was dedicated to the development of non-technical skills in the everyday activity of breast surgeons. We briefly discuss information from this very interesting and inspiring educational event and how it relates to more recent changes in surgical oncology education. PMID:25903052

  19. Limbic system development underlies the emergence of classical fear conditioning during the 3rd and 4th weeks of life in the rat

    PubMed Central

    Deal, Alex L.; Erickson, Kristen J.; Shiers, Stephanie I.; Burman, Michael A.

    2016-01-01

    Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats. Rat pups were fear conditioned, or not, during the 3rd or 4th weeks of life. Neuronal activation was assessed by quantifying expression of FBJ osteosarcoma oncogene (FOS) using immunohistochemistry (IHC) in Experiment 1. Fos and early growth response gene-1 (EGR1) expression was assessed using qRT-PCR in Experiment 2. Behavioral data confirm that both auditory and contextual fear continue to emerge between PD 17 and 24. The IEG expression data are highly consistent with these behavioral results. IHC results demonstrate significantly more FOS protein expression in the basal amygdala of fear conditioned PD 23 subjects compared to control subjects, but no significant difference at PD 17. qRT-PCR results suggest specific activation of the amygdala only in older subjects during auditory fear expression. A similar effect of age and conditioning status was also observed in the perirhinal cortex during both contextual and auditory fear expression. Overall, the development of fear conditioning occurring between the 3rd and 4th weeks of life appears to be at least partly attributable to changes in activation of the amygdala and perirhinal cortex during fear conditioning or expression. PMID:26820587

  20. Knowledge and institutional requirements to promote land degradation neutrality in drylands - An analysis of the outcomes of the 3rd UNCCD scientific conference

    NASA Astrophysics Data System (ADS)

    Akhtar-Schuster, Mariam; Safriel, Uriel; Abraham, Elena; de Vente, Joris; Essahli, Wafa; Escadafal, Richard; Stringer, Lindsay

    2015-04-01

    Achieving land degradation neutrality (LDN) through sustainable land management (SLM) targets the maintenance or restoration of the productivity of land, and therefore has to include decision-makers, knowledge generators and knowledge holders at the different relevant geographic scales. In order to enhance the implementation of the Convention, the Conference of the Parties (COP) of the United Nations Convention to Combat Desertification therefore decided that each future session of its Committee on Science and Technology (CST) would be organized in a predominantly scientific and technical conference-style format. This contribution will outline the major outcomes of UNCCD's 3rd scientific conference that will be held in Cancún, Mexico, from 9 to 12 March 2015, on addressing desertification, land degradation and drought issues (DLDD) for poverty reduction and sustainable development. The conference follows an exceptional new round table conference format that will allow the various stakeholders to discuss scientific as well as the contribution of traditional knowledge and practices in combating land degradation. This format should provide two-way communication and enable deeper insight into the availability and contribution of all forms of knowledge for achieving LDN through the assessment of: • the vulnerability of lands to DLDD and climate change and the adaptive capacities of socio-ecosystems; • best examples of adapted, knowledge-based practices and technologies; • monitoring and assessment methods to evaluate the effectiveness of adaptation practices and technologies. The outcomes of UNCCD's 3rd scientific conference will serve as a basis for discussing: • contributions of science to diagnose the status of land; • research gaps that need to be addressed to achieve LDN for poverty reduction; • additional institutional requirements to optimally bridge knowledge generation, knowledge maintenance and knowledge implementation at the science

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

    SciTech Connect

    Medori, R.; Tritschler, H.J. )

    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.

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

    PubMed Central

    Medori, R; Tritschler, H J

    1993-01-01

    Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp)-->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. We confirmed the 178Asn 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 178Asn 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-Sträussler 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 129Met/Val. Moreover, of five 178Asn individuals who are above age-at-onset range and who are well, two have 129Met and three have 129Met/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 178Asn mutation. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8105681

  3. Veterinary Microbiology, 3rd Edition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Veterinary Microbiology, Third Edition is organized into four sections and begins with an updated and expanded introductory section on infectious disease pathogenesis, diagnosis and clinical management. The second section covers bacterial and fungal pathogens, and the third section describes viral d...

  4. Landman's encyclopedia. 3rd edition

    SciTech Connect

    Hankinson, R.L.; Hankinson, R.L. Jr.

    1987-01-01

    This book discusses the guidelines for petroleum landmen and includes the new documents: partial assignment of oil, gas, and mineral lease, net profits agreement, net profit interest, ratification agreements, an additional farmout agreement form, gas balancing agreement, shut-in gas royalty, oil, gas, and mineral lease form (Exxon lease), extension agreement, Pugh clause, assignment form of lease and equipment, losses addendum for operating agreements, boundary agreement, change of lease description forms. Also included is a cross-listing of the document numbers used in this book with those used in the popular software database.

  5. An empirical test of the concomitantly variable codon hypothesis

    PubMed Central

    Merlo, Lauren M. F.; Lunzer, Mark; Dean, Antony M.

    2007-01-01

    A central assumption of models of molecular evolution, that each site in a sequence evolves independently of all other sites, lacks empirical support. We investigated the extent to which sites evolve codependently in triosephosphate isomerase (TIM), a ubiquitous glycolytic enzyme conserved in both structure and function. Codependencies among sites, or concomitantly variable codons (covarions), are evident from the reduced function and misfolding of hybrid TIM proteins. Although they exist, we find covarions are relatively rare, and closely related proteins are unlikely to have developed them. However, the potential for covarions increases with genetic distance so that highly divergent proteins may have evolved codependencies between many sites. The evolution of covarions undermines a key assumption in phylogenetics and calls into question our ability to disentangle ancient relationships among major taxonomic groups. PMID:17578921

  6. Attenuation of Tick-Borne Encephalitis Virus Using Large-Scale Random Codon Re-encoding

    PubMed Central

    de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

    2015-01-01

    Large-scale codon re-encoding (i.e. introduction of a large number of synonymous mutations) is a novel method of generating attenuated viruses. Here, it was applied to the pathogenic flavivirus, tick-borne encephalitis virus (TBEV) which causes febrile illness and encephalitis in humans in forested regions of Europe and Asia. Using an infectious clone of the Oshima 5–10 strain ("wild-type virus"), a cassette of 1.4kb located in the NS5 coding region, was modified by randomly introducing 273 synonymous mutations ("re-encoded virus"). Whilst the in cellulo replicative fitness of the re-encoded virus was only slightly reduced, the re-encoded virus displayed an attenuated phenotype in a laboratory mouse model of non-lethal encephalitis. Following intra-peritoneal inoculation of either 2.105 or 2.106 TCID50 of virus, the frequency of viraemia, neurovirulence (measured using weight loss and appearance of symptoms) and neuroinvasiveness (detection of virus in the brain) were significantly decreased when compared with the wild-type virus. Mice infected by wild-type or re-encoded viruses produced comparable amounts of neutralising antibodies and results of challenge experiments demonstrated that mice previously infected with the re-encoded virus were protected against subsequent infection by the wild-type virus. This constitutes evidence that a mammalian species can be protected against infection by a virulent wild-type positive-stranded RNA virus following immunisation with a derived randomly re-encoded strain. Our results demonstrate that random codon re-encoding is potentially a simple and effective method of generating live-attenuated vaccine candidates against pathogenic flaviviruses. PMID:25734338

  7. Polymorphism at codon 117 of the granulocyte-macrophage colony-stimulating factor gene (GM-CSF)

    SciTech Connect

    Tagiev, A.F.; Surin, V.L.; Osokina, A.V.

    1995-10-01

    A T-to-C substitution, replacing a hydrophobic isoleucine residue with a hydrophilic threonine residue in position 100 of a mature protein molecule, was found at codon 117 of the GM-CSF gene. The mutation frequencies were estimated in 51 DNA samples from healthy adult donors and also in 20 samples from patients with different neoplastic myeloid disorders. Almost equal substitution frequencies in patients and normal individuals were observed, suggesting that the defect was not associated with leukemia. Additionally, the GM-CSF gene intron 1 sequence was refined. 44 refs., 2 tabs.

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

    PubMed

    Karniychuk, Uladzimir U

    2016-09-01

    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. PMID:27364082

  9. Selective Factors Associated with the Evolution of Codon Usage in Natural Populations of Arboviruses.

    PubMed

    Velazquez-Salinas, Lauro; Zarate, Selene; Eschbaumer, Michael; Pereira Lobo, Francisco; Gladue, Douglas P; Arzt, Jonathan; Novella, Isabel S; Rodriguez, Luis L

    2016-01-01

    Arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. Most arboviruses utilize RNA for their genetic material and are completely dependent on host tRNAs for their translation, suggesting that virus codon usage could be a target for selection. In the current study we analyzed the relative synonymous codon usage (RSCU) patterns of 26 arboviruses together with 25 vectors and hosts, including 8 vertebrates and 17 invertebrates. We used hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify trends in codon usage. HCA demonstrated that the RSCU of arboviruses reflects that of their natural hosts, but not that of dead-end hosts. Of the two major components identified by PCA, the first accounted for 62.1% of the total variance, and among the 59 codons analyzed in this study, the leucine codon CTG had the highest correlation with the first principal component, however isoleucine had the highest correlation during amino acid analysis. Nucleotide and dinucleotide composition were the variables that explained most of the total codon usage variance. The results suggest that the main factors driving the evolution of codon usage in arboviruses is based on the nucleotide and dinucleotide composition present in the host. Comparing codon usage of arboviruses and potential vector hosts can help identifying potential vectors for emerging arboviruses. PMID:27455096

  10. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness

    NASA Astrophysics Data System (ADS)

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-06-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development.

  11. Selective Factors Associated with the Evolution of Codon Usage in Natural Populations of Arboviruses

    PubMed Central

    Velazquez-Salinas, Lauro; Zarate, Selene; Eschbaumer, Michael; Pereira Lobo, Francisco; Gladue, Douglas P.; Arzt, Jonathan; Novella, Isabel S.; Rodriguez, Luis L.

    2016-01-01

    Arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. Most arboviruses utilize RNA for their genetic material and are completely dependent on host tRNAs for their translation, suggesting that virus codon usage could be a target for selection. In the current study we analyzed the relative synonymous codon usage (RSCU) patterns of 26 arboviruses together with 25 vectors and hosts, including 8 vertebrates and 17 invertebrates. We used hierarchical cluster analysis (HCA) and principal component analysis (PCA) to identify trends in codon usage. HCA demonstrated that the RSCU of arboviruses reflects that of their natural hosts, but not that of dead-end hosts. Of the two major components identified by PCA, the first accounted for 62.1% of the total variance, and among the 59 codons analyzed in this study, the leucine codon CTG had the highest correlation with the first principal component, however isoleucine had the highest correlation during amino acid analysis. Nucleotide and dinucleotide composition were the variables that explained most of the total codon usage variance. The results suggest that the main factors driving the evolution of codon usage in arboviruses is based on the nucleotide and dinucleotide composition present in the host. Comparing codon usage of arboviruses and potential vector hosts can help identifying potential vectors for emerging arboviruses. PMID:27455096

  12. Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD.

    PubMed

    Fu, Jingjing; Murphy, Katherine A; Zhou, Mian; Li, Ying H; Lam, Vu H; Tabuloc, Christine A; Chiu, Joanna C; Liu, Yi

    2016-08-01

    Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage "code" within genetic codons to regulate cotranslational protein folding. PMID:27542830

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously identified the mycobacterial high G+C codon usage bias as a limiting factor in heterologous expression of MAP proteins from Lb.salivarius, and demonstrated that codon optimisation of a synthetic coding gene greatly enhances MAP protein production. Here, we effectively demonstrate ...

  14. Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding.

    PubMed

    Yu, Chien-Hung; Dang, Yunkun; Zhou, Zhipeng; Wu, Cheng; Zhao, Fangzhou; Sachs, Matthew S; Liu, Yi

    2015-09-01

    Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy, and protein folding based on the assumption that codon usage affects translation dynamics. The roles of codon usage in translation, however, are not clear and have been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the preferred codons enhance the rate of translation elongation, whereas non-optimal codons slow elongation. Codon usage also controls ribosome traffic on mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with template mRNAs designed to increase the signal-to-noise ratio. Finally, we demonstrate that codon usage regulates protein function by affecting co-translational protein folding. These results resolve a long-standing fundamental question and suggest the existence of a codon usage code for protein folding. PMID:26321254

  15. Characterization of codon usage pattern and influencing factors in Japanese encephalitis virus.

    PubMed

    Singh, Niraj K; Tyagi, Anuj; Kaur, Rajinder; Verma, Ramneek; Gupta, Praveen K

    2016-08-01

    Recently, several outbreaks of Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), have been reported and it has become cause of concern across the world. In this study, detailed analysis of JEV codon usage pattern was performed. The relative synonymous codon usage (RSCU) values along with mean effective number of codons (ENC) value of 55.30 indicated the presence of low codon usages bias in JEV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations of A3s, U3s, G3s, C3s, GC3s, ENC values, with overall nucleotide contents (A%, U%, G%, C%, and GC%). The correlation analysis of A3s, U3s, G3s, C3s, GC3s, with axis values of correspondence analysis (CoA) further confirmed the role of mutational pressure. However, the correlation analysis of Gravy values and Aroma values with A3s, U3s, G3s, C3s, and GC3s, indicated the presence of natural selection on codon usage bias in addition to mutational pressure. The natural selection was further confirmed by codon adaptation index (CAI) analysis. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent. PMID:27189042

  16. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness

    PubMed Central

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-01-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID:27278133

  17. Polypeptide release factors and stop codon recognition in the apicoplast and mitochondrion of Plasmodium falciparum.

    PubMed

    Vaishya, Suniti; Kumar, Vikash; Gupta, Ankit; Siddiqi, Mohammad Imran; Habib, Saman

    2016-06-01

    Correct termination of protein synthesis would be a critical step in translation of organellar open reading frames (ORFs) of the apicoplast and mitochondrion of the malaria parasite. We identify release factors (RFs) responsible for recognition of the UAA and UGA stop-codons of apicoplast ORFs and the sole UAA stop-codon that terminates translation from the three mitochondrial ORFs. A single nuclear-encoded canonical RF2, PfRF2Api , localizes to the apicoplast. It has a conserved tripeptide motif (SPF) for stop-codon recognition and is sufficient for peptidyl-tRNA hydrolysis (PTH) from both UAA and UGA. Two RF family proteins are targeted to the parasite mitochondrion; a canonical RF1, PfRF1Mit , with a variant codon-recognition motif (PxN instead of the conserved RF1 PxT) is the major peptidyl-hydrolase with specific recognition of the UAA codon relevant to mitochondrial ORFs. Mutation of the N residue of the PfRF1Mit PxN motif and two other conserved residues of the codon recognition domain lowers PTH activity from pre-termination ribosomes indicating their role in codon-recognition. The second RF imported by the mitochondrion is the non-canonical PfICT1 that functions as a dimer and mediates codon nonspecific peptide release. Our results help delineate a critical step in organellar translation in Plasmodium, which is an important target for anti-malarials. PMID:26946524

  18. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness.

    PubMed

    Villanueva, Eneko; Martí-Solano, Maria; Fillat, Cristina

    2016-01-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID:27278133

  19. A Large Number of Nuclear Genes in the Human Parasite Blastocystis Require mRNA Polyadenylation to Create Functional Termination Codons

    PubMed Central

    Klimeš, Vladimír; Gentekaki, Eleni; Roger, Andrew J.; Eliáš, Marek

    2014-01-01

    Termination codons in mRNA molecules are typically specified directly by the sequence of the corresponding gene. However, in mitochondria of a few eukaryotic groups, some mRNAs contain the termination codon UAA deriving one or both adenosines from transcript polyadenylation. Here, we show that a similar phenomenon occurs for a substantial number of nuclear genes in Blastocystis spp., divergent unicellular eukaryote gut parasites. Our analyses of published genomic data from Blastocystis sp. subtype 7 revealed that polyadenylation-mediated creation of termination codons occurs in approximately 15% of all nuclear genes. As this phenomenon has not been noticed before, the procedure previously employed to annotate the Blastocystis nuclear genome sequence failed to correctly define the structure of the 3′-ends of hundreds of genes. From sequence data we have obtained from the distantly related Blastocystis sp. subtype 1 strain, we show that this phenomenon is widespread within the Blastocystis genus. Polyadenylation in Blastocystis appears to be directed by a conserved GU-rich element located four nucleotides downstream of the polyadenylation site. Thus, the highly precise positioning of the polyadenylation in Blastocystis has allowed reduction of the 3′-untranslated regions to the point that, in many genes, only one or two nucleotides of the termination codon are left. PMID:25015079

  20. A Kinesthetic Learning Approach to Earth Science for 3rd and 4th Grade Students on the Pajarito Plateau, Los Alamos, NM

    NASA Astrophysics Data System (ADS)

    Wershow, H. N.; Green, M.; Stocker, A.; Staires, D.

    2010-12-01

    Current efforts towards Earth Science literacy in New Mexico are guided by the New Mexico Science Benchmarks [1]. We are geoscience professionals in Los Alamos, NM who believe there is an important role for non-traditional educators utilizing innovative teaching methods. We propose to further Earth Science literacy for local 3rd and 4th grade students using a kinesthetic learning approach, with the goal of fostering an interactive relationship between the students and their geologic environment. We will be working in partnership with the Pajarito Environmental Education Center (PEEC), which teaches the natural heritage of the Pajarito Plateau to 3rd and 4th grade students from the surrounding area, as well as the Family YMCA’s Adventure Programs Director. The Pajarito Plateau provides a remarkable geologic classroom because minimal structural features complicate the stratigraphy and dramatic volcanic and erosional processes are plainly on display and easily accessible. Our methodology consists of two approaches. First, we will build an interpretive display of the local geology at PEEC that will highlight prominent rock formations and geologic processes seen on a daily basis. It will include a simplified stratigraphic section with field specimens and a map linked to each specimen’s location to encourage further exploration. Second, we will develop and implement a kinesthetic curriculum for an exploratory field class. Active engagement with geologic phenomena will take place in many forms, such as a scavenger hunt for precipitated crystals in the vesicles of basalt flows and a search for progressively smaller rhyodacite clasts scattered along an actively eroding canyon. We believe students will be more receptive to origin explanations when they possess a piece of the story. Students will be provided with field books to make drawings of geologic features. This will encourage independent assessment of phenomena and introduce the skill of scientific observation. We

  1. Importance of codon usage for the temporal regulation of viral gene expression.

    PubMed

    Shin, Young C; Bischof, Georg F; Lauer, William A; Desrosiers, Ronald C

    2015-11-10

    The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products. PMID:26504241

  2. Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation.

    PubMed

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

    2016-09-15

    Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD. PMID:27275533

  3. Evidence for Stabilizing Selection on Codon Usage in Chromosomal Rearrangements of Drosophila pseudoobscura

    PubMed Central

    Fuller, Zachary L.; Haynes, Gwilym D.; Zhu, Dianhui; Batterton, Matthew; Chao, Hsu; Dugan, Shannon; Javaid, Mehwish; Jayaseelan, Joy C.; Lee, Sandra; Li, Mingmei; Ongeri, Fiona; Qi, Sulan; Han, Yi; Doddapaneni, Harshavardhan; Richards, Stephen; Schaeffer, Stephen W.

    2014-01-01

    There has been a renewed interest in investigating the role of stabilizing selection acting on genome-wide traits such as codon usage bias. Codon bias, when synonymous codons are used at unequal frequencies, occurs in a wide variety of taxa. Standard evolutionary models explain the maintenance of codon bias through a balance of genetic drift, mutation and weak purifying selection. The efficacy of selection is expected to be reduced in regions of suppressed recombination. Contrary to observations in Drosophila melanogaster, some recent studies have failed to detect a relationship between the recombination rate, intensity of selection acting at synonymous sites, and the magnitude of codon bias as predicted under these standard models. Here, we examined codon bias in 2798 protein coding loci on the third chromosome of D. pseudoobscura using whole-genome sequences of 47 individuals, representing five common third chromosome gene arrangements. Fine-scale recombination maps were constructed using more than 1 million segregating sites. As expected, recombination was demonstrated to be significantly suppressed between chromosome arrangements, allowing for a direct examination of the relationship between recombination, selection, and codon bias. As with other Drosophila species, we observe a strong mutational bias away from the most frequently used codons. We find the rate of synonymous and nonsynonymous polymorphism is variable between different amino acids. However, we do not observe a reduction in codon bias or the strength of selection in regions of suppressed recombination as expected. Instead, we find that the interaction between weak stabilizing selection and mutational bias likely plays a role in shaping the composition of synonymous codons across the third chromosome in D. pseudoobscura. PMID:25326424

  4. The perceptions of professional soccer players on the risk of injury from competition and training on natural grass and 3rd generation artificial turf

    PubMed Central

    2014-01-01

    Background The purpose of this study was to describe professional soccer players’ perceptions towards injuries, physical recovery and the effect of surface related factors on injury resulting from soccer participation on 3rd generation artificial turf (FT) compared to natural grass (NG). Methods Information was collected through a questionnaire that was completed by 99 professional soccer players from 6 teams competing in Major League Soccer (MLS) during the 2011 season. Results The majority (93% and 95%) of the players reported that playing surface type and quality influenced the risk of sustaining an injury. Players believed that playing and training on FT increased the risk of sustaining a non-contact injury as opposed to a contact injury. The players identified three surface related risk factors on FT, which they related to injuries and greater recovery times: 1) Greater surface stiffness 2) Greater surface friction 3) Larger metabolic cost to playing on artificial grounds. Overall, 94% of the players chose FT as the surface most likely to increase the risk of sustaining an injury. Conclusions Players believe that the risk of injury differs according to surface type, and that FT is associated with an increased risk of non-contact injury. Future studies should be designed prospectively to systematically track the perceptions of groups of professional players training and competing on FT and NG. PMID:24581229

  5. Stable Isotope and Trace Element Studies on Gladiators and Contemporary Romans from Ephesus (Turkey, 2nd and 3rd Ct. AD) - Implications for Differences in Diet

    PubMed Central

    Lösch, Sandra; Moghaddam, Negahnaz; Grossschmidt, Karl; Risser, Daniele U.; Kanz, Fabian

    2014-01-01

    The gladiator cemetery discovered in Ephesus (Turkey) in 1993 dates to the 2nd and 3rd century AD. The aim of this study is to reconstruct diverse diet, social stratification, and migration of the inhabitants of Roman Ephesus and the distinct group of gladiators. Stable carbon, nitrogen, and sulphur isotope analysis were applied, and inorganic bone elements (strontium, calcium) were determined. In total, 53 individuals, including 22 gladiators, were analysed. All individuals consumed C3 plants like wheat and barley as staple food. A few individuals show indication of consumption of C4 plants. The δ13C values of one female from the gladiator cemetery and one gladiator differ from all other individuals. Their δ34S values indicate that they probably migrated from another geographical region or consumed different foods. The δ15N values are relatively low in comparison to other sites from Roman times. A probable cause for the depletion of 15N in Ephesus could be the frequent consumption of legumes. The Sr/Ca-ratios of the gladiators were significantly higher than the values of the contemporary Roman inhabitants. Since the Sr/Ca-ratio reflects the main Ca-supplier in the diet, the elevated values of the gladiators might suggest a frequent use of a plant ash beverage, as mentioned in ancient texts. PMID:25333366

  6. Evidence of human-induced morphodynamic changes along the Campania coastal areas (southern Italy) since the 3rd-4th cent. AD

    NASA Astrophysics Data System (ADS)

    Russo Ermolli, Elda; Romano, Paola; Liuzza, Viviana; Amato, Vincenzo; Ruello, Maria Rosaria; Di Donato, Valentino

    2014-05-01

    Campania has always offered suitable climatic and physiographic conditions for human settlements since prehistoric times. In particular, many Graeco-Roman towns developed along its coasts starting from the 7th-6th cent. BC. In the last decade, geoarchaelogical surveys have been carried out in the archaeological excavations of Neapolis, Paestum and Elea-Velia allowing the main steps of the landscape evolution around these towns to be defined in detail. The greek town of Neapolis rose in the late 6th cent. BC [1] on a terrace overlooking a low-relief rocky coast surrounded by volcanic hills. Port activities developed in a protected bay facing the town from the 4th-2nd cent. BC up to the 4th cent. AD, as testified by the discovery of structures and shipwrecks [2, 3, 4]. Starting from the 3rd cent. AD a spit bar formed at the bay entrance causing the progressive establishment of a lagoon which was gradually filled up by alluvial inputs and completely closed in the 5th cent. AD. During the same period, episodes of increased alluvial inputs were also recorded further west along the coast, where a narrow sandy beach formed at the cliff toe. The greek town of Poseidonia, renamed Paestum by the Romans, was founded in the 540 BC on a travertine terrace facing the sandy littoral of a prograding coastal plain [5]. In front of the main town door, a coastal lagoon developed thanks to the growth of a dune ridge and was probably used for harbor activities [5]. After this period the shoreline shifted seawards, another dune ridge formed and the back-ridge depression was filled with fluvial-marshy deposits, slowly drying up. Phases of travertine deposition, which characterized the SE sector of the plain all along the Holocene, were recorded in the northern and southern quarters of the town in historical times and were connected to the abandonment of the town in the early Medieval times. The greek colony of Elea-Velia was located on top of a siliciclastic promontory where the ruins of

  7. In vitro effects of three woody plant and sainfoin extracts on 3rd-stage larvae and adult worms of three gastrointestinal nematodes.

    PubMed

    Paolini, V; Fouraste, I; Hoste, H

    2004-07-01

    Most studies on the effects of tanniferous plants on nematodes have examined forages but have neglected the woody plants. Therefore, in vitro effects of extracts from 3 woody plants (Rubus fructicosus, Quercus robur, Corylus avellana) have been tested on trichostrongyles and compared to sainfoin, a legume forage. Because some in vivo results indicated that the effects of tannins differed depending on the parasitic species and/or stages, the effects were measured on 3rd-stage larvae (L3) and adult worms of Teladorsagia circumcincta, Haemonchlus contortus and Trichostrongylus colubriformis. The effects of plant extracts varied according to the plant sources, the parasite species and stages. For the woody plants, significant inhibitory effects were obtained on both stages of abomasal species. Results for T. colubriformis were more variable. Effects of sainfoin extracts were significant on T. colubriformis and H. contortus L3, and on abomasal adult worms. In order to assess the implications of tannins, polyethylene glycol (PEG), an inhibitor of tannins, was added to hazel tree, oak and sainfoin extracts. Without PEG, significant inhibitory effects on L3 and adult worms were confirmed. After addition of PEG, the larval migration and motility of adult worms were restored in most cases. These results confirm variations in effects depending on factors related to plants or parasites and suggest that tannins are partly responsible for the effects. PMID:15267113

  8. Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species

    PubMed Central

    Mazumder, Tarikul Huda; Chakraborty, Supriyo

    2015-01-01

    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. PMID:25807269

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

    PubMed Central

    Liu, Jibin; Zhu, Dekang; Ma, Guangpeng; Liu, Mafeng; Wang, Mingshu; Jia, Renyong; Chen, Shun; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    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. PMID:27517915

  10. A Comparative Analysis of Synonymous Codon Usage Bias Pattern in Human Albumin Superfamily

    PubMed Central

    Mirsafian, Hoda; Mat Ripen, Adiratna; Singh, Aarti; Teo, Phaik Hwan; Merican, Amir Feisal; Mohamad, Saharuddin Bin

    2014-01-01

    Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life. Though the frequency of codon usage is not equal across species and within genome in the same species, the phenomenon is non random and is tissue-specific. Several factors such as GC content, nucleotide distribution, protein hydropathy, protein secondary structure, and translational selection are reported to contribute to codon usage preference. The synonymous codon usage patterns can be helpful in revealing the expression pattern of genes as well as the evolutionary relationship between the sequences. In this study, synonymous codon usage bias patterns were determined for the evolutionarily close proteins of albumin superfamily, namely, albumin, α-fetoprotein, afamin, and vitamin D-binding protein. Our study demonstrated that the genes of the four albumin superfamily members have low GC content and high values of effective number of codons (ENC) suggesting high expressivity of these genes and less bias in codon usage preferences. This study also provided evidence that the albumin superfamily members are not subjected to mutational selection pressure. PMID:24707212

  11. Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States

    PubMed Central

    Villar, Diego; White, Robert J.; Marioni, John C.; Kutter, Claudia

    2016-01-01

    Whether codon usage fine-tunes mRNA translation in mammals remains controversial, with recent papers suggesting that production of proteins in specific Gene Ontological (GO) pathways can be regulated by actively modifying the codon and anticodon pools in different cellular conditions. In this work, we compared the sequence content of genes in specific GO categories with the exonic genome background. Although a substantial fraction of variability in codon usage could be explained by random sampling, almost half of GO sets showed more variability in codon usage than expected by chance. Nevertheless, by quantifying translational efficiency in healthy and cancerous tissues in human and mouse, we demonstrated that a given tRNA pool can equally well translate many different sets of mRNAs, irrespective of their cell-type specificity. This disconnect between variations in codon usage and the stability of translational efficiency is best explained by differences in GC content between gene sets. GC variation across the mammalian genome is most likely a result of the interplay between genome repair and gene duplication mechanisms, rather than selective pressures caused by codon-driven translational rates. Consequently, codon usage differences in mammalian transcriptomes are most easily explained by well-understood mutational biases acting on the underlying genome. PMID:27166679

  12. Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes.

    PubMed

    Iwane, Yoshihiko; Hitomi, Azusa; Murakami, Hiroshi; Katoh, Takayuki; Goto, Yuki; Suga, Hiroaki

    2016-04-01

    In ribosomal polypeptide synthesis the library of amino acid building blocks is limited by the manner in which codons are used. Of the proteinogenic amino acids, 18 are coded for by multiple codons and therefore many of the 61 sense codons can be considered redundant. Here we report a method to reduce the redundancy of codons by artificially dividing codon boxes to create vacant codons that can then be reassigned to non-proteinogenic amino acids and thereby expand the library of genetically encoded amino acids. To achieve this, we reconstituted a cell-free translation system with 32 in vitro transcripts of transfer RNASNN (tRNASNN) (S = G or C), assigning the initiator and 20 elongator amino acids. Reassignment of three redundant codons was achieved by replacing redundant tRNASNNs with tRNASNNs pre-charged with non-proteinogenic amino acids. As a demonstration, we expressed a 32-mer linear peptide that consists of 20 proteinogenic and three non-proteinogenic amino acids, and a 14-mer macrocyclic peptide that contains more than four non-proteinogenic amino acids. PMID:27001726

  13. Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes

    NASA Astrophysics Data System (ADS)

    Iwane, Yoshihiko; Hitomi, Azusa; Murakami, Hiroshi; Katoh, Takayuki; Goto, Yuki; Suga, Hiroaki

    2016-04-01

    In ribosomal polypeptide synthesis the library of amino acid building blocks is limited by the manner in which codons are used. Of the proteinogenic amino acids, 18 are coded for by multiple codons and therefore many of the 61 sense codons can be considered redundant. Here we report a method to reduce the redundancy of codons by artificially dividing codon boxes to create vacant codons that can then be reassigned to non-proteinogenic amino acids and thereby expand the library of genetically encoded amino acids. To achieve this, we reconstituted a cell-free translation system with 32 in vitro transcripts of transfer RNASNN (tRNASNN) (S = G or C), assigning the initiator and 20 elongator amino acids. Reassignment of three redundant codons was achieved by replacing redundant tRNASNNs with tRNASNNs pre-charged with non-proteinogenic amino acids. As a demonstration, we expressed a 32-mer linear peptide that consists of 20 proteinogenic and three non-proteinogenic amino acids, and a 14-mer macrocyclic peptide that contains more than four non-proteinogenic amino acids.

  14. Transcription attenuation in Salmonella typhimurium: the significance of rare leucine codons in the leu leader.

    PubMed Central

    Carter, P W; Bartkus, J M; Calvo, J M

    1986-01-01

    The leucine operon of Salmonella typhimurium is controlled by a transcription attenuation mechanism. Four adjacent leucine codons within a 160-nucleotide leu leader RNA are thought to play a central role in this mechanism. Three of the four codons are CUA, a rarely used leucine codon within enteric bacteria. To determine whether the nature of the leucine codon affects the regulation of the leucine operon, we used oligonucleotide-directed mutagenesis to first convert one CUA of the leader to CUG and then convert all three CUA codons to CUG. CUG is the most frequently used leucine codon in enteric bacteria. A mutant having (CUA)2CUGCUC in place of (CUA)3CUC has an altered response to leucine limitation, requiring a slightly higher degree of limitation to effect derepression. Changing (CUA)3CUC to (CUG)3CUC has more dramatic effects upon operon expression. First, the basal level of expression is lowered to the point that the mutant grows more slowly than the parent in a minimal medium lacking leucine. Second, the response of the mutant to a leucine limitation is dramatically altered such that even a strong limitation elicits only a modest degree of derepression. If the mutant is grown under conditions of leucyl-tRNA limitation rather than leucine limitation, complete derepression can be achieved, but only at a much higher degree of limitation than for the wild-type operon. These results provide a clear-cut example of codon usage having a dramatic effect upon gene expression. PMID:3534884

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

    PubMed

    Liu, Jibin; Zhu, Dekang; Ma, Guangpeng; Liu, Mafeng; Wang, Mingshu; Jia, Renyong; Chen, Shun; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    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. PMID:27517915

  16. Polymorphism distribution of prion protein codon 117, 129 and 171 in Taiwan.

    PubMed

    Wang, Kaw-Chen; Wang, Vinchi; Sun, Ming-Chieh; Chiueh, Ti-I; Soong, Bing-Wen; Shan, Din-E

    2007-01-01

    Prion diseases compass transmissible spongiform neurodegenerative diseases from various causes, including the genetic and infectious ones. We investigated the prevalence of codon 117, 129 and 171 polymorphism in prion protein (PrP) in Taiwanese, mainly for the sake of the informative absence of this genetic distribution. Our subjects were 419 aged ones of Han ethic origin. We evaluated the PrP gene (PRNP) polymorphism by restriction fragment length polymorphism, after amplification of their genomic DNAs by polymerase chain reactions with specific primers, digested by restriction enzyme PvuII (for codon 117), NspI (for codon 129), and BbvI (for codon 171), respectively, and confirmed by nucleotide sequencing. All of the subjects were homozygotes at codon 117 (Ala/Ala, gca/gca) and 171 (Asn/Asn, aac/aac). There were no valine homozygotes (Val/Val) in our 419 subjects, and nine subjects (2.1%) showed methionine-valine heterozygosity (Mal/Val, atg/gtg). The methionine homozygotes (Met/Met) comprised the major population (97.9%), and the prevalence of distribution is different to that seen in Caucasians. The almost 100% conservation of the domain from codon 117 to 171 implies the warranty of PrP in cellular functions. The high prevalence of Met/Met alleles in Taiwan did not imply an increased risk of CJD, and the genetic susceptibility of CJD by codon 129 of PrP may be still elusive for the infectivity. PMID:17410475

  17. A bacterial strain with a unique quadruplet codon specifying non-native amino acids.

    PubMed

    Chatterjee, Abhishek; Lajoie, Marc J; Xiao, Han; Church, George M; Schultz, Peter G

    2014-08-18

    The addition of noncanonical amino acids to the genetic code requires unique codons not assigned to the 20 canonical amino acids. Among the 64 triplet codons, only the three nonsense "stop" codons have been used to encode non-native amino acids. Use of quadruplet "frame-shift" suppressor codons provides an abundant alternative but suffers from low suppression efficiency as a result of competing recognition of their first three bases by endogenous host tRNAs or release factors. Deletion of release factor 1 in a genomically recoded strain of E. coli (E. coli C321), in which all endogenous amber stop codons (UAG) are replaced with UAA, abolished UAG mediated translation termination. Here we show that a Methanocaldococcus jannaschii-derived frame-shift suppressor tRNA/aminoacyl-tRNA synthetase pair enhanced UAGN suppression efficiency in this recoded bacterial strain. These results demonstrate that efficient quadruplet codons for encoding non-native amino acids can be generated by eliminating competing triplet codon recognition at the ribosome. PMID:24867343

  18. Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast.

    PubMed

    Gamble, Caitlin E; Brule, Christina E; Dean, Kimberly M; Fields, Stanley; Grayhack, Elizabeth J

    2016-07-28

    Translation elongation efficiency is largely thought of as the sum of decoding efficiencies for individual codons. Here, we find that adjacent codon pairs modulate translation efficiency. Deploying an approach in Saccharomyces cerevisiae that scored the expression of over 35,000 GFP variants in which three adjacent codons were randomized, we have identified 17 pairs of adjacent codons associated with reduced expression. For many pairs, codon order is obligatory for inhibition, implying a more complex interaction than a simple additive effect. Inhibition mediated by adjacent codons occurs during translation itself as GFP expression is restored by increased tRNA levels or by non-native tRNAs with exact-matching anticodons. Inhibition operates in endogenous genes, based on analysis of ribosome profiling data. Our findings suggest translation efficiency is modulated by an interplay between tRNAs at adjacent sites in the ribosome and that this concerted effect needs to be considered in predicting the functional consequences of codon choice. PMID:27374328

  19. SwiftLib: rapid degenerate-codon-library optimization through dynamic programming

    PubMed Central

    Jacobs, Timothy M.; Yumerefendi, Hayretin; Kuhlman, Brian; Leaver-Fay, Andrew

    2015-01-01

    Degenerate codon (DC) libraries efficiently address the experimental library-size limitations of directed evolution by focusing diversity toward the positions and toward the amino acids (AAs) that are most likely to generate hits; however, manually constructing DC libraries is challenging, error prone and time consuming. This paper provides a dynamic programming solution to the task of finding the best DCs while keeping the size of the library beneath some given limit, improving on the existing integer-linear programming formulation. It then extends the algorithm to consider multiple DCs at each position, a heretofore unsolved problem, while adhering to a constraint on the number of primers needed to synthesize the library. In the two library-design problems examined here, the use of multiple DCs produces libraries that very nearly cover the set of desired AAs while still staying within the experimental size limits. Surprisingly, the algorithm is able to find near-perfect libraries where the ratio of amino-acid sequences to nucleic-acid sequences approaches 1; it effectively side-steps the degeneracy of the genetic code. Our algorithm is freely available through our web server and solves most design problems in about a second. PMID:25539925

  20. Tryptophan Codon-Dependent Transcription in Chlamydia pneumoniae during Gamma Interferon-Mediated Tryptophan Limitation.

    PubMed

    Ouellette, Scot P; Rueden, Kelsey J; Rucks, Elizabeth A

    2016-09-01

    In evolving to an obligate intracellular niche, Chlamydia has streamlined its genome by eliminating superfluous genes as it relies on the host cell for a variety of nutritional needs like amino acids. However, Chlamydia can experience amino acid starvation when the human host cell in which the bacteria reside is exposed to interferon gamma (IFN-γ), which leads to a tryptophan (Trp)-limiting environment via induction of the enzyme indoleamine-2,3-dioxygenase (IDO). The stringent response is used to respond to amino acid starvation in most bacteria but is missing from Chlamydia Thus, how Chlamydia, a Trp auxotroph, responds to Trp starvation in the absence of a stringent response is an intriguing question. We previously observed that C. pneumoniae responds to this stress by globally increasing transcription while globally decreasing translation, an unusual response. Here, we sought to understand this and hypothesized that the Trp codon content of a given gene would determine its transcription level. We quantified transcripts from C. pneumoniae genes that were either rich or poor in Trp codons and found that Trp codon-rich transcripts were increased, whereas those that lacked Trp codons were unchanged or even decreased. There were exceptions, and these involved operons or large genes with multiple Trp codons: downstream transcripts were less abundant after Trp codon-rich sequences. These data suggest that ribosome stalling on Trp codons causes a negative polar effect on downstream sequences. Finally, reassessing previous C. pneumoniae microarray data based on codon content, we found that upregulated transcripts were enriched in Trp codons, thus supporting our hypothesis. PMID:27400720

  1. The unfolded protein response affects readthrough of premature termination codons

    PubMed Central

    Oren, Yifat S; McClure, Michelle L; Rowe, Steven M; Sorscher, Eric J; Bester, Assaf C; Manor, Miriam; Kerem, Eitan; Rivlin, Joseph; Zahdeh, Fouad; Mann, Matthias; Geiger, Tamar; Kerem, Batsheva

    2014-01-01

    One-third of monogenic inherited diseases result from premature termination codons (PTCs). Readthrough of in-frame PTCs enables synthesis of full-length functional proteins. However, extended variability in the response to readthrough treatment is found among patients, which correlates with the level of nonsense transcripts. Here, we aimed to reveal cellular pathways affecting this inter-patient variability. We show that activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts carrying PTCs. Quantitative proteomic analyses showed substantial differences in UPR activation between patients carrying PTCs, correlating with their response. We further found a significant inverse correlation between the UPR and nonsense-mediated mRNA decay (NMD), suggesting a feedback loop between these homeostatic pathways. We uncovered and characterized the mechanism underlying this NMD-UPR feedback loop, which augments both UPR activation and NMD attenuation. Importantly, this feedback loop enhances the response to readthrough treatment, highlighting its clinical importance. Altogether, our study demonstrates the importance of the UPR and its regulatory network for genetic diseases caused by PTCs and for cell homeostasis under normal conditions. PMID:24705877

  2. Suppression of Premature Termination Codons as a Therapeutic Approach

    PubMed Central

    Keeling, Kim M.; Wang, Dan; Conard, Sara E.; Bedwell, David M.

    2012-01-01

    In this review, we describe our current understanding of translation termination and pharmacological agents that influence the accuracy of this process. A number of drugs have been identified that induce suppression of translation termination at in-frame premature termination codons (PTCs; also known as nonsense mutations) in mammalian cells. We discuss efforts to utilize these drugs to suppress disease-causing PTCs that result in the loss of protein expression and function. In-frame PTCs represent a genotypic subset of mutations that make up ~11% of all known mutations that cause genetic diseases, and millions of patients have diseases attributable to PTCs. Current approaches aimed at reducing the efficiency of translation termination at PTCs (referred to as PTC suppression therapy) have the goal of alleviating the phenotypic consequences of a wide range of genetic diseases. Suppression therapy is currently in clinical trials for treatment of several genetic diseases caused by PTCs, and preliminary results suggest that some patients have shown clinical improvements. While current progress is promising, we discuss various approaches that may further enhance the efficiency of this novel therapeutic approach. PMID:22672057

  3. The characteristics of synonymous codon usage in the initial and terminal translation regions of encephalomyocarditis virus.

    PubMed

    Ma, X-X; Feng, Y-P; Liu, J-L; Zhao, Y-Q; Chen, L; Guo, P-H; Guo, J-Z; Ma, Z-R

    2014-01-01

    The synonymous codon usage patterns in the initial and terminal translation regions (ITR, TTR) of the whole coding sequence of encephalomyocarditis virus (EMCV) were analyzed in relation to those in its natural hosts using the sequences accessible in databases. In general, some low-usage host codons were found over-represented in the ITR and TTR of the virus, while some high-usage host codons were found under-represented in the two viral regions. These relationships are thought to participate in the regulation of the speed of translation of viral proteins and in the suppression of ribosomal traffic jams, both aiming at the increase of virus yields. PMID:24720745

  4. Stellar Occultations by Large TNOs on 2012: The February 3rd by (208996) 2003 AZ84, and the February 17th by (50000) Quaoar

    NASA Astrophysics Data System (ADS)

    Braga Ribas, Felipe; Sicardy, B.; Ortiz, J. L.; Duffard, R.; Camargo, J. I. B.; Lecacheux, J.; Colas, F.; Vachier, F.; Tanga, P.; Sposetti, S.; Brosch, N.; Kaspi, S.; Manulis, I.; Baug, T.; Chandrasekhar, T.; Ganesh, S.; Jain, J.; Mohan, V.; Sharma, A.; Garcia-Lozano, R.; Klotz, A.; Frappa, E.; Jehin, E.; Assafin, M.; Vieira Martins, R.; Behrend, R.; Roques, F.; Widemann, T.; Morales, N.; Thirouin, A.; Mahasena, P.; Benkhaldoun, Z.; Daassou, A.; Rinner, C.; Ofek, E. O.

    2012-10-01

    On February 2012, two stellar occultation's by large Trans-neptunian Objects (TNO's) were observed by our group. On the 3rd, an event by (208996) 2003 AZ84 was recorded from Mont Abu Observatory and IUCAA Girawali Observatory in India and from Weizmann Observatory in Israel. On the 17th, a stellar occultation by (50000) Quaoar was observed from south France and Switzerland. Both occultations are the second observed by our group for each object, and will be used to improve the results obtained on the previous events. The occultation by 2003 AZ84 is the first multi-chord event recorded for this object. From the single chord event on January 8th 2011, Braga-Ribas et al. 2011 obtained a lower limit of 573 +/- 21 km. From the 2012 occultation the longest chord has a size of 662 +/- 50 km. The other chords will permit to determine the size and shape of the TNO, and derive other physical parameters, such as the geometric albedo. The Quaoar occultation was observed from south of France (Observatoire de la Côte d'Azur, TAROT telescope and Valensole) and from Gnosca, Switzerland. Unfortunately, all three sites in France are almost at the same Quaoar's latitude, so in practice, we have two chords that can be used to fit Quaoar's limb. The resulting fit will be compared with the results obtained by Braga-Ribas et al. 2011. Braga-Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060.Ribas F., Sicardy B., et al. 2011, EPSC-DPS2011, 1060.

  5. Medical school curriculum characteristics associated with intentions and frequency of tobacco dependence treatment among 3rd year U.S. medical students

    PubMed Central

    Hayes, Rashelle B.; Geller, Alan C.; Crawford, Sybil L.; Jolicoeur, Denise; Churchill, Linda C.; Okuyemi, Kola; David, Sean P.; Adams, Michael; Waugh, Jonathan; Allen, Sharon S.; Leone, Frank T.; Fauver, Randy; Leung, Katherine; Liu, Qin; Ockene, Judith K.

    2015-01-01

    Objective Physicians play a critical role in addressing tobacco dependence, yet report limited training. Tobacco dependence treatment curricula for medical students could improve performance in this area. This study identified student and medical school tobacco treatment curricula characteristics associated with intentions and use of the 5As for tobacco treatment among 3rd year U.S. medical students. Methods Third year medical students (N=1065, 49.3% male) from 10 U.S. medical schools completed a survey in 2009-2010 assessing student characteristics, including demographics, tobacco treatment knowledge, and self-efficacy. Tobacco curricula characteristics assessed included amount and type of classroom instruction, frequency of tobacco treatment observation, instruction, and perception of preceptors as role models. Results Greater tobacco treatment knowledge, self-efficacy, and curriculum-specific variables were associated with 5A intentions, while younger age, tobacco treatment self-efficacy, intentions, and each curriculum-specific variable was associated with greater 5A behaviors. When controlling for important student variables, greater frequency of receiving 5A instruction (OR = 1.07; 95%CI 1.01-1.12) and perception of preceptors as excellent role models in tobacco treatment (OR = 1.35; 95%CI 1.04-1.75) were significant curriculum predictors of 5A intentions. Greater 5A instruction (B = .06 (.03); p< .05) and observation of tobacco treatment (B= .35 (.02); p< .001) were significant curriculum predictors of greater 5A behaviors. Conclusions Greater exposure to tobacco treatment teaching during medical school is associated with both greater intentions to use and practice tobacco 5As. Clerkship preceptors, or those physicians who provide training to medical students, may be particularly influential when they personally model and instruct students in tobacco dependence treatment. PMID:25572623

  6. US Marine 3rd Tank Battalion lubrication evaluation under hot ambient temperatures at Twenty-Nine Palms, California. Interim report, April-September 1988

    SciTech Connect

    Butler, W.E.; Owens, E.C.; Frame, E.A.; Bowen, T.C.

    1988-09-01

    Military Specification MIL-L-2104D, Lubricating Oil, Internal Combustion Engines, Tactical Service, was released 1 April 1983. This specification included a multiviscosity OE/HDO-15/40 oil and eliminated a previously authorized OE/HDO-50 oil. The manufacturer of the AVDS-1790 series engines used in M60 battle tanks and M88 tank retrievers raised raised concerns about warranty coverage. The U.S. Marine Corps indicated that the use of the authorized 15W-40 grade oil did not offer sufficient lubrication for the engines and also resulted in M60 final drive leaks. As a result of these concerns, the U.S. Army Belvoir Research, Development and Engineering Center (Belvoir RDE Center) authorized an oil comparison test that, by agreement with the U.S. Marine Corps, would be conducted at the U.S. Marine Corps Air-Ground Combat Center (USMCAGCC) at Twenty-Nine Palms, CA using the U.S. Marine 3rd Tank Battalion (3DTKBn). The test vehicles of A Company, 3DTKBn were charged with regular issue 50-grade oil in the engine, 10-grade oil in the transmission, and 50-grade oil in the M60 final drives. B Company's test vehicles were charged with 15W-40 grade oil in the engines, transmissions, and M60 final drives. C Company's test vehicles were charged with 40-grade oil in the engines, 10-grade oil in the transmissions, and 50-grade oil in the final drives. Results from this 4-month test indicated no discernible differences in engine or transmission operating temperatures, engine oil pressures, or M60 final drive leaks.

  7. Non-destructive measurement of demineralization and remineralization in the occlusal pits and fissures of extracted 3rd molars with PS-OCT

    NASA Astrophysics Data System (ADS)

    Lee, Chulsung; Hsu, Dennis J.; Le, Michael H.; Darling, Cynthia L.; Fried, Daniel

    2009-02-01

    Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image the remineralization of early artificial caries lesion on smooth enamel surfaces of human and bovine teeth. However, most new dental decay is found in the pits and fissures of the occlusal surfaces of posterior dentition and it is in these high risk areas where the performance of new caries imaging devices need to be investigated. The purpose of this study was to demonstrate that PS-OCT can be used to measure the subsequent remineralization of artificial lesions produced in the pits and fissures of extracted 3rd molars. A PS-OCT system operating at 1310-nm was used to acquire polarization resolved images of occlusal surfaces exposed to a demineralizing solution at pH-4.5 followed by a fluoride containing remineralizing solution at pH-7.0 containing 2-ppm fluoride. The integrated reflectivity was calculated to a depth of 200-µm in the entire lesion area using an automated image processing algorithm. Although a well-defined surface zone was clearly resolved in only a few of the samples that underwent remineralization, the PS-OCT measurements indicated a significant (p<0.05) reduction in the integrated reflectivity between the severity of the lesions that were exposed to the remineralization solution and those that were not. The lesion depth and mineral loss were also measured with polarized light microscopy and transverse microradiography after sectioning the teeth. These results show that PS-OCT can be used to non-destructively monitor the remineralization potential of anti-caries agents in the important pits and fissures of the occlusal surface.

  8. A novel amperometric alcohol biosensor developed in a 3rd generation bioelectrode platform using peroxidase coupled ferrocene activated alcohol oxidase as biorecognition system.

    PubMed

    Chinnadayyala, Somasekhar R; Kakoti, Ankana; Santhosh, Mallesh; Goswami, Pranab

    2014-05-15

    Alcohol oxidase (AOx) with a two-fold increase in efficiency (Kcat/Km) was achieved by physical entrapment of the activator ferrocene in the protein matrix through a simple microwave based partial unfolding technique and was used to develop a 3rd generation biosensor for improved detection of alcohol in liquid samples. The ferrocene molecules were stably entrapped in the AOx protein matrix in a molar ratio of ~3:1 through electrostatic interaction with the Trp residues involved in the functional activity of the enzyme as demonstrated by advanced analytical techniques. The sensor was fabricated by immobilizing ferrocene entrapped alcohol oxidase (FcAOx) and sol-gel chitosan film coated horseradish peroxidase (HRP) on a multi-walled carbon nanotube (MWCNT) modified glassy carbon electrode through layer-by-layer technique. The bioelectrode reactions involved the formation of H2O2 by FcAOx biocatalysis of substrate alcohol followed by HRP-catalyzed reduction of the liberated H2O2 through MWCNT supported direct electron transfer mechanism. The amperometric biosensor exhibited a linear response to alcohol in the range of 5.0 × 10(-6) to 30 × 10(-4)mol L(-1) with a detection limit of 2.3 × 10(-6) mol L(-1), and a sensitivity of 150 µA mM(-1) cm(-2). The biosensor response was steady for 28 successive measurements completed in a period of 5h and retained ~90% of the original response even after four weeks when stored at 4 °C. The biosensor was successfully applied for the determination of alcohol in commercial samples and its performance was validated by comparing with the data obtained by GC analyses of the samples. PMID:24368229

  9. Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells.

    PubMed

    Ang, Kok Siong; Kyriakopoulos, Sarantos; Li, Wei; Lee, Dong-Yup

    2016-06-01

    In this study, we analyzed multi-omics data and subsets thereof to establish reference codon usage biases for codon optimization in synthetic gene design. Specifically, publicly available genomic, transcriptomic, proteomic and translatomic data for microbial and mammalian expression hosts, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Chinese hamster ovary (CHO) cells, were compiled to derive their individual codon and codon pair frequencies. Then, host dependent and -omics specific codon biases were generated and compared by principal component analysis and hierarchical clustering. Interestingly, our results indicated the similar codon bias patterns of the highly expressed transcripts, highly abundant proteins, and efficiently translated mRNA in microbial cells, despite the general lack of correlation between mRNA and protein expression levels. However, for CHO cells, the codon bias patterns among various -omics subsets are not distinguishable, forming one cluster. Thus, we further investigated the effect of different input codon biases on codon optimized sequences using the codon context (CC) and individual codon usage (ICU) design parameters, via in silico case study on the expression of human IFNγ sequence in CHO cells. The results supported that CC is more robust design parameter than ICU for improved heterologous gene design. PMID:26850284

  10. Role of codon choice in the leader region of the ilvGMEDA operon of Serratia marcescens.

    PubMed Central

    Harms, E; Umbarger, H E

    1987-01-01

    Leucine participates in multivalent repression of the Serratia marcescens ilvGMEDA operon by attenuation (J.-H. Hsu, E. Harms, and H.E. Umbarger, J. Bacteriol. 164:217-222, 1985), although there is only one single leucine codon that could be involved in this type of control. This leucine codon is the rarely used CUA. The contribution of this leucine codon to the control of transcription by attenuation was examined by replacing it with the commonly used leucine codon CUG and with a nonregulatory proline codon, CCG. These changes left intact the proposed secondary structure of the leader. The effects of the codon changes were assessed by placing the mutant leader regions upstream of the ilvGME structural genes or the cat gene and measuring acetohydroxy acid synthase II, transaminase B, or chloramphenicol acetyltransferase activities in cells grown under limiting and repressing conditions. The presence of the common leucine codon in place of the rare leucine codon reduced derepression by about 70%. Eliminating the leucine codon by converting it to proline abolished leucine control. Furthermore, a possible context effect of the adjacent upstream serine codon on leucine control was examined by changing it into a glycine codon. PMID:2824442

  11. CodHonEditor: Spreadsheets for Codon Optimization and Editing of Protein Coding Sequences.

    PubMed

    Takai, Kazuyuki

    2016-05-01

    Gene synthesis is getting more important with the growing availability of low-cost commercial services. The coding sequences are often "optimized" as for the relative synonymous codon usage (RSCU) before synthesis, which is generally included in the commercial services. However, the codon optimization processes are different among different providers and are often hidden from the users. Here, the d'Hondt method, which is widely adopted as a method for determining the number of seats for each party in proportional-representation public elections, is applied to RSCU fitting. This allowed me to make a set of electronic spreadsheets for manual design of protein coding sequences for expression in Escherichia coli, with which users can see the process of codon optimization and can manually edit the codons after the automatic optimization. The spreadsheets may also be useful for molecular biology education. PMID:27002987

  12. 18. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, BUILT 189x. ...

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

    18. WEST CONFEDERATE AVENUE BRIDGE SPANNING CODON'S RUN, BUILT 189x. NOTE STRAIGHT ASHLAR COURSING AND RAISED KEYSTONES. VIEW NW. - Gettysburg National Military Park Tour Roads, Gettysburg, Adams County, PA

  13. Usage of the three termination codons in a single eukaryotic cell, the Xenopus laevis oocyte.

    PubMed Central

    Bienz, M; Kubli, E; Kohli, J; deHenau, S; Huez, G; Marbaix, G; Grosjean, H

    1981-01-01

    Oocytes from Xenopus laevis were injected with purified amber (UAG), ochre (UAA), and opal (UGA) suppressor tRNAs from yeasts. The radioactively labeled proteins translated from the endogenous mRNAs were then separated on two-dimensional gels. All three termination codons are used in a single cell, the Xenopus laevis oocyte. But a surprisingly low number of readthrough polypeptides were observed from the 600 mRNAs studied in comparison to uninjected oocytes. The experimental data are compared with the conclusions obtained from the compilation of all available termination sequences on eukaryotic and prokaryotic mRNAs. This comparison indicates that the apparent resistance of natural termination codons against readthrough, as observed by the microinjection experiments, cannot be explained by tandem or very close second stop codons. Instead it suggests that specific context sequences around the termination codons may play a role in the efficiency of translation termination. Images PMID:7024919

  14. Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes

    PubMed Central

    Hinnebusch, Alan G.

    2011-01-01

    Summary: The correct translation of mRNA depends critically on the ability to initiate at the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the 5′ end of the mRNA and then inspects the leader base by base for an AUG in a suitable context, using complementarity with the anticodon of methionyl initiator tRNA (Met-tRNAiMet) as the key means of identifying AUG. Over the past decade, a combination of yeast genetics, biochemical analysis in reconstituted systems, and structural biology has enabled great progress in deciphering the mechanism of ribosomal scanning. A robust molecular model now exists, describing the roles of initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in stabilizing an “open” conformation of the 40S subunit with Met-tRNAiMet bound in a low-affinity state conducive to scanning and in triggering rearrangement into a “closed” conformation incompatible with scanning, which features Met-tRNAiMet more tightly bound to the “P” site and base paired with AUG. It has also emerged that multiple DEAD-box RNA helicases participate in producing a single-stranded “landing pad” for the 40S subunit and in removing the secondary structure to enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded form for base-by-base inspection in the P site. PMID:21885680

  15. Metabolic engineering of E.coli for the production of a precursor to artemisinin, an anti-malarial drug [Chapter 25 in Manual of Industrial Microbiology and Biotechnology, 3rd edition

    SciTech Connect

    Petzold, Christopher; Keasling, Jay

    2011-07-18

    This document is Chapter 25 in the Manual of Industrial Microbiology and Biotechnology, 3rd edition. Topics covered include: Incorporation of Amorpha-4,11-Diene Biosynthetic Pathway into E. coli; Amorpha-4,11-Diene Pathway Optimization; "-Omics" Analyses for Increased Amorpha-4,11-Diene Production; Biosynthetic Oxidation of Amorpha-4,11-Diene.

  16. An improved DNA-based test for detection of the codon 616 mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive retinal atrophy in the Cardigan Welsh Corgi.

    PubMed

    Petersen-Jones, Simon M; Entz, David D

    2002-06-01

    The aim of the study was to develop an improved test to detect the codon 616 gene mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive retinal atrophy in the Cardigan Welsh Corgi. We studied 10 control dogs of known genotype at codon 616 of the alpha cyclic GMP phosphodiesterase gene and 80 Cardigan Welsh Corgis of unknown genotype. A polymerase chain reaction (PCR) utilizing a mismatched primer was designed so that it introduced a HinfI restriction enzyme digestion site into the PCR product only if the normal gene sequence was present, the restriction site was not introduced if the codon 616 mutation was present. An additional HinfI site present in the amplified section from both normal and mutant alleles acted as a positive control for restriction enzyme digestion. The PCR reliably amplified a portion of the alpha cyclic GMP phosphodiesterase gene spanning the codon 616 mutation site. Restriction enzyme digestion with HinfI and analysis on a suitable agarose gel reliably ascertained the genotype of the control dogs and was used to identify the genotype of a further 80 test dogs. An improved DNA-based test for detection of the codon 616 mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive retinal atrophy in the Cardigan Welsh Corgi has been designed. This overcomes potential problems that could be associated with allele-specific PCR tests such as that used previously in a diagnostic test for this gene mutation. PMID:12071867

  17. Codon and Amino Acid Usage Are Shaped by Selection Across Divergent Model Organisms of the Pancrustacea.

    PubMed

    Whittle, Carrie A; Extavour, Cassandra G

    2015-11-01

    In protein-coding genes, synonymous codon usage and amino acid composition correlate to expression in some eukaryotes, and may result from translational selection. Here, we studied large-scale RNA-seq data from three divergent arthropod models, including cricket (Gryllus bimaculatus), milkweed bug (Oncopeltus fasciatus), and the amphipod crustacean Parhyale hawaiensis, and tested for optimization of codon and amino acid usage relative to expression level. We report strong signals of AT3 optimal codons (those favored in highly expressed genes) in G. bimaculatus and O. fasciatus, whereas weaker signs of GC3 optimal codons were found in P. hawaiensis, suggesting selection on codon usage in all three organisms. Further, in G. bimaculatus and O. fasciatus, high expression was associated with lowered frequency of amino acids with large size/complexity (S/C) scores in favor of those with intermediate S/C values; thus, selection may favor smaller amino acids while retaining those of moderate size for protein stability or conformation. In P. hawaiensis, highly transcribed genes had elevated frequency of amino acids with large and small S/C scores, suggesting a complex dynamic in this crustacean. In all species, the highly transcribed genes appeared to favor short proteins, high optimal codon usage, specific amino acids, and were preferentially involved in cell-cycling and protein synthesis. Together, based on examination of 1,680,067, 1,667,783, and 1,326,896 codon sites in G. bimaculatus, O. fasciatus, and P. hawaiensis, respectively, we conclude that translational selection shapes codon and amino acid usage in these three Pancrustacean arthropods. PMID:26384771

  18. Codon and Amino Acid Usage Are Shaped by Selection Across Divergent Model Organisms of the Pancrustacea

    PubMed Central

    Whittle, Carrie A.; Extavour, Cassandra G.

    2015-01-01

    In protein-coding genes, synonymous codon usage and amino acid composition correlate to expression in some eukaryotes, and may result from translational selection. Here, we studied large-scale RNA-seq data from three divergent arthropod models, including cricket (Gryllus bimaculatus), milkweed bug (Oncopeltus fasciatus), and the amphipod crustacean Parhyale hawaiensis, and tested for optimization of codon and amino acid usage relative to expression level. We report strong signals of AT3 optimal codons (those favored in highly expressed genes) in G. bimaculatus and O. fasciatus, whereas weaker signs of GC3 optimal codons were found in P. hawaiensis, suggesting selection on codon usage in all three organisms. Further, in G. bimaculatus and O. fasciatus, high expression was associated with lowered frequency of amino acids with large size/complexity (S/C) scores in favor of those with intermediate S/C values; thus, selection may favor smaller amino acids while retaining those of moderate size for protein stability or conformation. In P. hawaiensis, highly transcribed genes had elevated frequency of amino acids with large and small S/C scores, suggesting a complex dynamic in this crustacean. In all species, the highly transcribed genes appeared to favor short proteins, high optimal codon usage, specific amino acids, and were preferentially involved in cell-cycling and protein synthesis. Together, based on examination of 1,680,067, 1,667,783, and 1,326,896 codon sites in G. bimaculatus, O. fasciatus, and P. hawaiensis, respectively, we conclude that translational selection shapes codon and amino acid usage in these three Pancrustacean arthropods. PMID:26384771

  19. A yeast tRNA mutant that causes pseudohyphal growth exhibits reduced rates of CAG codon translation

    PubMed Central

    Kemp, Alain J; Betney, Russell; Ciandrini, Luca; Schwenger, Alexandra C M; Romano, M Carmen; Stansfield, Ian

    2013-01-01

    In Saccharomyces cerevisiae, the SUP70 gene encodes the CAG-decoding tRNAGlnCUG. A mutant allele, sup70-65, induces pseudohyphal growth on rich medium, an inappropriate nitrogen starvation response. This mutant tRNA is also a UAG nonsense suppressor via first base wobble. To investigate the basis of the pseudohyphal phenotype, 10 novel sup70 UAG suppressor alleles were identified, defining positions in the tRNAGlnCUG anticodon stem that restrict first base wobble. However, none conferred pseudohyphal growth, showing altered CUG anticodon presentation cannot itself induce pseudohyphal growth. Northern blot analysis revealed the sup70-65 tRNAGlnCUG is unstable, inefficiently charged, and 80% reduced in its effective concentration. A stochastic model simulation of translation predicted compromised expression of CAG-rich ORFs in the tRNAGlnCUG-depleted sup70-65 mutant. This prediction was validated by demonstrating that luciferase expression in the mutant was 60% reduced by introducing multiple tandem CAG (but not CAA) codons into this ORF. In addition, the sup70-65 pseudohyphal phenotype was partly complemented by overexpressing CAA-decoding tRNAGlnUUG, an inefficient wobble-decoder of CAG. We thus show that introducing codons decoded by a rare tRNA near the 5′ end of an ORF can reduce eukaryote translational expression, and that the mutant tRNACUGGln constitutive pseudohyphal differentiation phenotype correlates strongly with reduced CAG decoding efficiency. PMID:23146061

  20. A yeast tRNA mutant that causes pseudohyphal growth exhibits reduced rates of CAG codon translation.

    PubMed

    Kemp, Alain J; Betney, Russell; Ciandrini, Luca; Schwenger, Alexandra C M; Romano, M Carmen; Stansfield, Ian

    2013-01-01

    In Saccharomyces cerevisiae, the SUP70 gene encodes the CAG-decoding tRNA(Gln)(CUG). A mutant allele, sup70-65, induces pseudohyphal growth on rich medium, an inappropriate nitrogen starvation response. This mutant tRNA is also a UAG nonsense suppressor via first base wobble. To investigate the basis of the pseudohyphal phenotype, 10 novel sup70 UAG suppressor alleles were identified, defining positions in the tRNA(Gln)(CUG) anticodon stem that restrict first base wobble. However, none conferred pseudohyphal growth, showing altered CUG anticodon presentation cannot itself induce pseudohyphal growth. Northern blot analysis revealed the sup70-65 tRNA(Gln)(CUG) is unstable, inefficiently charged, and 80% reduced in its effective concentration. A stochastic model simulation of translation predicted compromised expression of CAG-rich ORFs in the tRNA(Gln)(CUG)-depleted sup70-65 mutant. This prediction was validated by demonstrating that luciferase expression in the mutant was 60% reduced by introducing multiple tandem CAG (but not CAA) codons into this ORF. In addition, the sup70-65 pseudohyphal phenotype was partly complemented by overexpressing CAA-decoding tRNA(Gln)(UUG), an inefficient wobble-decoder of CAG. We thus show that introducing codons decoded by a rare tRNA near the 5' end of an ORF can reduce eukaryote translational expression, and that the mutant tRNA(CUG)(Gln) constitutive pseudohyphal differentiation phenotype correlates strongly with reduced CAG decoding efficiency. PMID:23146061

  1. Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

    PubMed Central

    Bali, Vedrana; Bebok, Zsuzsanna

    2015-01-01

    Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

  2. Reassignment of a rare sense codon to a non-canonical amino acid in Escherichia coli

    PubMed Central

    Mukai, Takahito; Yamaguchi, Atsushi; Ohtake, Kazumasa; Takahashi, Mihoko; Hayashi, Akiko; Iraha, Fumie; Kira, Satoshi; Yanagisawa, Tatsuo; Yokoyama, Shigeyuki; Hoshi, Hiroko; Kobayashi, Takatsugu; Sakamoto, Kensaku

    2015-01-01

    The immutability of the genetic code has been challenged with the successful reassignment of the UAG stop codon to non-natural amino acids in Escherichia coli. In the present study, we demonstrated the in vivo reassignment of the AGG sense codon from arginine to l-homoarginine. As the first step, we engineered a novel variant of the archaeal pyrrolysyl-tRNA synthetase (PylRS) able to recognize l-homoarginine and l-N6-(1-iminoethyl)lysine (l-NIL). When this PylRS variant or HarRS was expressed in E. coli, together with the AGG-reading tRNAPylCCU molecule, these arginine analogs were efficiently incorporated into proteins in response to AGG. Next, some or all of the AGG codons in the essential genes were eliminated by their synonymous replacements with other arginine codons, whereas the majority of the AGG codons remained in the genome. The bacterial host's ability to translate AGG into arginine was then restricted in a temperature-dependent manner. The temperature sensitivity caused by this restriction was rescued by the translation of AGG to l-homoarginine or l-NIL. The assignment of AGG to l-homoarginine in the cells was confirmed by mass spectrometric analyses. The results showed the feasibility of breaking the degeneracy of sense codons to enhance the amino-acid diversity in the genetic code. PMID:26240376

  3. Evidence of codon usage in the nearest neighbor spacing distribution of bases in bacterial genomes

    NASA Astrophysics Data System (ADS)

    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.

  4. Correction of Methylmalonic Aciduria In Vivo Using a Codon-Optimized Lentiviral Vector

    PubMed Central

    Wong, Edward S.Y.; McIntyre, Chantelle; Peters, Heidi L.; Ranieri, Enzo; Anson, Donald S.

    2014-01-01

    Abstract Methylmalonic aciduria is a rare disorder of organic acid metabolism with limited therapeutic options, resulting in high morbidity and mortality. Positive results from combined liver/kidney transplantation suggest, however, that metabolic sink therapy may be efficacious. Gene therapy offers a more accessible approach for the treatment of methylmalonic aciduria than organ transplantation. Accordingly, we have evaluated a lentiviral vector–mediated gene transfer approach in an in vivo mouse model of methylmalonic aciduria. A mouse model of methylmalonic aciduria (Mut−/−MUTh2) was injected intravenously at 8 weeks of age with a lentiviral vector that expressed a codon-optimized human methylmalonyl coenzyme A mutase transgene, HIV-1SDmEF1αmurSigHutMCM. Untreated Mut−/−MUTh2 and normal mice were used as controls. HIV-1SDmEF1αmurSigHutMCM-treated mice achieved near-normal weight for age, and Western blot analysis demonstrated significant methylmalonyl coenzyme A enzyme expression in their livers. Normalization of liver methylmalonyl coenzyme A enzyme activity in the treated group was associated with a reduction in plasma and urine methylmalonic acid levels, and a reduction in the hepatic methylmalonic acid concentration. Administration of the HIV-1SDmEF1αmurSigHutMCM vector provided significant, although incomplete, biochemical correction of methylmalonic aciduria in a mouse model, suggesting that gene therapy is a potential treatment for this disorder. PMID:24568291

  5. Mechanisms of the tRNA wobble cytidine modification essential for AUA codon decoding in prokaryotes.

    PubMed

    Numata, Tomoyuki

    2015-01-01

    Bacteria and archaea have 2-lysylcytidine (L or lysidine) and 2-agmatinylcytidine (agm(2)C or agmatidine), respectively, at the first (wobble) position of the anticodon of the AUA codon-specific tRNA(Ile). These lysine- or agmatine-conjugated cytidine derivatives are crucial for the precise decoding of the genetic code. L is synthesized by tRNA(Ile)-lysidine synthetase (TilS), which uses l-lysine and ATP as substrates. Agm(2)C formation is catalyzed by tRNA(Ile)-agm(2)C synthetase (TiaS), which uses agmatine and ATP for the reaction. Despite the fact that TilS and TiaS synthesize structurally similar cytidine derivatives, these enzymes belong to non-related protein families. Therefore, these enzymes modify the wobble cytidine by distinct catalytic mechanisms, in which TilS activates the C2 carbon of the wobble cytidine by adenylation, while TiaS activates it by phosphorylation. In contrast, TilS and TiaS share similar tRNA recognition mechanisms, in which the enzymes recognize the tRNA acceptor stem to discriminate tRNA(Ile) and tRNA(Met). PMID:25348586

  6. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population

    PubMed Central

    Ban, Yoshiyuki; Taniyama, Matsuo; Yanagawa, Tatsuo; Yamada, Satoru; Maruyama, Taro; Kasuga, Akira; Ban, Yoshio

    2001-01-01

    Background Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated associations between the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We carried out polymerase chain reaction-restriction fragment length polymorphism analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies were assessed in 78 patients with T1DM. Results We found a significantly higher prevalence of the F allele / the FF genotype in the patients compared to the controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele frequencies differed significantly between GAD65-Ab-positive patients and controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab-negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively). Conclusions Our findings suggest that the vitamin D receptor initiation codon polymorphism influences genetic susceptibility to T1DM among the Japanese. This polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence of a significant difference between GAD65-Ab-negative patients and controls might be simply due to the small sample size of patients tested for GAD65 antibodies. PMID:11445000

  7. ICOM2012: 3rd International Conference on the Physics of Optical Materials and Devices (Belgrade, Serbia, 2-6 September 2012)

    NASA Astrophysics Data System (ADS)

    Dramićanin, Miroslav D.; Antić, Željka; Viana, Bruno

    2013-11-01

    The 3rd International Conference on the Physics of Optical Materials and Devices (ICOM2012) was held in Belgrade (Serbia) from 2 to 6 September 2012 (figure 1). The conference was organized by the Vinča Institute of Nuclear Sciences, University of Belgrade (Serbia) and the Laboratoire de Chimie de la Matière Condensée de Paris (France), and supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia and Optical Society of America. ICOM2012 was a follow-up to the two previous, successful ICOM conferences held in Herceg Novi in 2006 and 2009. The conference aimed at providing a forum for scientists in optical materials to debate on: • Luminescent materials and nanomaterials • Hybrid optical materials (organic/inorganic) • Characterization techniques of optical materials • Luminescence mechanisms and energy transfers • Theory and modeling of optical processes • Ultrafast-laser processing of materials • Optical sensors • Medical imaging • Advanced optical materials in photovoltaics and biophotonics • Photothermal and photoacoustic spectroscopy and phenomena The conference stressed the value of a fundamental scientific understanding of optical materials. A particular accent was put on wide band-gap materials in crystalline, glass and nanocrystalline forms. The applications mainly involved lasers, scintillators and phosphors. Rare earth and transition metal ions introduced as dopants in various hosts were considered, and their impact on the optical properties were detailed in several presentations. This volume contains selected contributions of speakers and participants of the ICOM2012 conference. The conference provided a unique opportunity for about 200 scientists from 32 countries to discuss recent progress in the field of optical materials. During the three and half days, 21 invited talks and 52 contributed lectures were given, with a special event in memory of our dear colleague Professor Dr Tsoltan

  8. Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

    PubMed Central

    Kwon, Inchan; Choi, Eun Sil

    2016-01-01

    Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

  9. Synonymous Codon Usage Affects the Expression of Wild Type and F508del CFTR

    PubMed Central

    Shah, Kalpit; Cheng, Yi; Hahn, Brian; Bridges, Robert; Bradbury, Neil; Mueller, David M.

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel composed of 1480 amino acids. The major mutation responsible for cystic fibrosis results in loss of amino acid residue, F508, (F508del). Loss of F508 in CFTR alters the folding pathway resulting in endoplasmic reticulum associated degradation (ERAD). This study investigates the role of synonymous codon in the expression of CFTR and CFTR F508del in human HEK293 cells. DNA encoding the open reading frame (ORF) for CFTR containing synonymous codon replacements, were expressed using a heterologous vector integrated into the genome. The results indicate that the codon usage greatly affects the expression of CFTR. While the promoter strength driving expression of the ORFs was largely unchanged and the mRNA half-lives were unchanged, the steady state levels of the mRNA varied by as much as 30 fold. Experiments support that this apparent inconsistency is attributed to exon junction complex independent nonsense mediated decay. The ratio of CFTR/mRNA indicates that mRNA containing native codons was more efficient in expressing mature CFTR as compared to mRNA containing synonymous high expression codons. However, when F508del CFTR was expressed after codon optimization, a greater percentage of the protein escaped ERAD resulting in considerable levels of mature F508del CFTR on the plasma membrane, which showed channel activity. These results indicate that for CFTR, codon usage has an effect on mRNA levels, protein expression and likely, for F508del CFTR, chaperone assisted folding pathway. PMID:25676312

  10. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy).

    PubMed Central

    Ahmad, N N; Ala-Kokko, L; Knowlton, R G; Jimenez, S A; Weaver, E J; Maguire, J I; Tasman, W; Prockop, D J

    1991-01-01

    Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein. Images PMID:1677770

  11. [Cold agglutinin disease -  no response to glucocorticoids and rituximab, what treatment is best for the 3rd line of therapy? Case report and review of the literature].

    PubMed

    Adam, Z; Pejchalová, A; Chlupová, G; Ríhová, L; Pour, L; Krejčí, M; Cervinek, L; Král, Z; Mayer, J

    2013-09-01

    in about one  half of treated patients and the remission duration median after rituximab administration is 11 months. A combination of rituximab with fludarabin was more effective, though more toxic; this combination, in a clinical study, led to 75% of patients responding to treatment, including 20% experiencing complete remission. The treatment response median reached over 66 months. In a small study (10 patients) an increase in the amount of rituximab administrations from 4 to 8 led to a treatment response in 6 patients in whom administration of 4 doses of rituximab had no response. When treating Waldenström macroglobulinemia, effectiveness of the following drugs and their combinations was proven: rituximab, chlorambucil, cyclophosphamide, fludarabin, bortezomib, lenalidomid, bendamustin and alemtuzumab. The same drugs and treatment procedures are used for the treatment of the cold agglutinin disease as for Waldenström macroglobulinemia. Successful treatment with vortezomibem, combinations of rituximab + bendamustin, rituximab + cyclophosphamide or rituximab + fludarabin + cyclophosphamide, were recorded in the form of a description as regards the cold agglutinin disease treatment. An important benefit is also shown through treatment with the monoclonal antibody antiC5, eculizumab, which is otherwise used for the treatment of paroxysmal nocturnal haemoglobinuria. Eculizumab blocks the C5 element of the component and thus stops haemolysis in a patient with cold agglutinin disease. As cold agglutinin disease is very rare, there are only a few clinical studies and when treating this rare disease we have no other option than to take into account the information contained in the descriptions of the particular cases of cold agglutinin disease and the experience of Waldenström macroglobulinemia disease treatment. The discussion seeks to solve the issue regarding what 3rd line treatment option to use in the described patient. PMID:24073955

  12. Joint conference of iMEC 2015 (2nd International Manufacturing Engineering Conference & APCOMS 2015 (3rd Asia-Pacific Conference on Manufacturing Systems)

    NASA Astrophysics Data System (ADS)

    2016-02-01

    The iMEC 2015 is the second International Manufacturing Engineering Conference organized by the Faculty of Manufacturing, Universiti Malaysia Pahang (UMP), held from 12-14th November 2015 in Kuala Lumpur, Malaysia, with a theme "Materials, Manufacturing and Systems for Tomorrow". For the first time, iMEC is organized together with 3rd Asia- Pacific Conference on Manufacturing System (APCOMS 2015) which owned by Fakulti Teknologi Industri, Institut Teknologi Bandung (ITB), Indonesia. This is an extended collaboration between UMP and ITB to intensify knowledge sharing and experiences between higher learning institutions. This conference (iMEC & APCOMS 2015) is a platform for knowledge exchange and the growth of ideas, particularly in manufacturing engineering. The conference aims to bring researchers, academics, scientists, students, engineers and practitioners from around the world together to present their latest findings, ideas, developments and applications related to manufacturing engineering and other related research areas. With rapid advancements in manufacturing engineering, iMEC is an appropriate medium for the associated community to keep pace with the changes. In 2015, the conference theme is “Materials, Manufacturing and Systems for Tomorrow” which reflects the acceleration of knowledge and technology in global manufacturing. The papers in these proceedings are examples of the work presented at the conference. They represent the tip of the iceberg, as the conference attracted over 200 abstracts from Malaysia, Indonesia, Japan, United Kingdom, Australia, India, Bangladesh, South Africa, Turkey and Morocco and 151 full papers were accepted in these proceedings. The conference was run in four parallel sessions with 160 presenters sharing their latest finding in the areas of manufacturing process, systems, advanced materials and automation. The first keynote presentation was given by Prof. B. S. Murthy (IIT, Madras) on "Nanomaterials with Exceptional

  13. Stages of Geoinformation Evolution Related to the Territories Described in the Bible - from the 3Rd Millennium B.C. to Modern Times

    NASA Astrophysics Data System (ADS)

    Linsenbarth, Adam

    2012-09-01

    The paper presents consecutive stages of the evolution of geoinformation related to the territories of the events described in the Bible. Two geoinformation sources are presented: the Bible and non-Bible sources. In the Bible there is much, often some highly detailed information regarding terrain topography. The oldest non-Bible sources are incorporated in the ancient documents, which were discovered in Egypt and Mesopotamia. Some of them are related to the 3rd millen- nium B.C. The further stages are related to the onomasticons and itineraries written by travellers and pilgrims to the Holy Land. The most famous onomasticons include: onomasticons prepared by bishop Eusebius from Caesarea and those pre- pared by St. Jerome. One of the oldest maps of Palestine's territory is the so-called mosaic map of Madaba dated to 565. In the 15th century several Bible maps were edited. The most rapid evolution occurred in the 16th and 17* centuries, when the world famous cartographers such as Mercator and Ortelius edited several maps of Palestine's territory. Cartographers from several European countries edited more than 6,000 maps presenting the Biblical territories and Biblical events. Modem maps, based on detailed topographical surveys, were edited m the second half of the 19* and 20th centuries. W artykule przedstawiono kolejne etapy rozwoju geoinformacji dotyczącej terenówr biblijnych. Omówiono dwa źródła informacji, a mianowicie geoinformacje biblijne i pozabiblijne. W tekstach biblijnych można znaleźć wiele, często bardzo detalicznych informacji topograficznych. Najstarsze źródła pozabiblijne, to starożytne dokumenty odnalezione na terenach Egiptu i Mezopotamii. Niektóre z nich pochodzą z trzeciego milenium przed Chr. Kolejnym etapem geoinformacji były onomastikony oraz dzienniki podróży pisane przez podróżników i pielgrzymów do Ziemi Świętej. Do najbardziej znanych należy onomastikon sporządzony przez biskupa Euzebiusza z Cezarei oraz

  14. Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR.

    PubMed

    Kianmehr, Anvarsadat; Golavar, Raziyeh; Rouintan, Mandana; Mahrooz, Abdolkarim; Fard-Esfahani, Pezhman; Oladnabi, Morteza; Khajeniazi, Safoura; Mostafavi, Seyede Samaneh; Omidinia, Eskandar

    2016-02-01

    Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse-transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC% content changed from 56% to 58%. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa. PMID:26546410

  15. Analysis of synonymous codon usage patterns in sixty-four different bivalve species

    PubMed Central

    De Moro, Gianluca; Venier, Paola; Pallavicini, Alberto

    2015-01-01

    Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates. PMID:26713259

  16. Codon influence on protein expression in E. coli correlates with mRNA levels.

    PubMed

    Boël, Grégory; Letso, Reka; Neely, Helen; Price, W Nicholson; Wong, Kam-Ho; Su, Min; Luff, Jon D; Valecha, Mayank; Everett, John K; Acton, Thomas B; Xiao, Rong; Montelione, Gaetano T; Aalberts, Daniel P; Hunt, John F

    2016-01-21

    Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli. PMID:26760206

  17. Non-universal decoding of the leucine codon CUG in several Candida species.

    PubMed Central

    Ohama, T; Suzuki, T; Mori, M; Osawa, S; Ueda, T; Watanabe, K; Nakase, T

    1993-01-01

    It has been reported that CUG, a universal leucine codon, is read as serine in an asporogenic yeast, Candida cylindracea. The distribution of this non-universal genetic code in various yeast species was studied using an in vitro translation assay system with a synthetic messenger RNA containing CUG codons in-frame. It was found that CUG is used as a serine codon in six out of the fourteen species examined, while it is used for leucine in the remaining eight. The tRNA species responsible for the translation of codon CUG as serine was detected in all the six species in which CUG is translated as serine. The grouping according to the CUG codon assignments in these yeast species shows a good correlation with physiological classification by the chain lengths of the isoprenoid moiety of ubiquinone and the cell-wall sugar contained in the yeasts. The six Candida species examined in which CUG is used as serine belong to one distinct group in Hemiascomycetes. PMID:8371978

  18. Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon.

    PubMed

    Katz, M J; Gándara, L; De Lella Ezcurra, A L; Wappner, P

    2016-05-01

    Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress. PMID:26874685

  19. The Effect of an Alternate Start Codon on Heterologous Expression of a PhoA Fusion Protein in Mycoplasma gallisepticum.

    PubMed

    Panicker, Indu S; Browning, Glenn F; Markham, Philip F

    2015-01-01

    While the genomes of many Mycoplasma species have been sequenced, there are no collated data on translational start codon usage, and the effects of alternate start codons on gene expression have not been studied. Analysis of the annotated genomes found that ATG was the most prevalent translational start codon among Mycoplasma spp. However in Mycoplasma gallisepticum a GTG start codon is commonly used in the vlhA multigene family, which encodes a highly abundant, phase variable lipoprotein adhesin. Therefore, the effect of this alternate start codon on expression of a reporter PhoA lipoprotein was examined in M. gallisepticum. Mutation of the start codon from ATG to GTG resulted in a 2.5 fold reduction in the level of transcription of the phoA reporter, but the level of PhoA activity in the transformants containing phoA with a GTG start codon was only 63% of that of the transformants with a phoA with an ATG start codon, suggesting that GTG was a more efficient translational initiation codon. The effect of swapping the translational start codon in phoA reporter gene expression was less in M. gallisepticum than has been seen previously in Escherichia coli or Bacillus subtilis, suggesting the process of translational initiation in mycoplasmas may have some significant differences from those used in other bacteria. This is the first study of translational start codon usage in mycoplasmas and the impact of the use of an alternate start codon on expression in these bacteria. PMID:26010086

  20. The Effect of an Alternate Start Codon on Heterologous Expression of a PhoA Fusion Protein in Mycoplasma gallisepticum

    PubMed Central

    Panicker, Indu S.; Browning, Glenn F.; Markham, Philip F.

    2015-01-01

    While the genomes of many Mycoplasma species have been sequenced, there are no collated data on translational start codon usage, and the effects of alternate start codons on gene expression have not been studied. Analysis of the annotated genomes found that ATG was the most prevalent translational start codon among Mycoplasma spp. However in Mycoplasma gallisepticum a GTG start codon is commonly used in the vlhA multigene family, which encodes a highly abundant, phase variable lipoprotein adhesin. Therefore, the effect of this alternate start codon on expression of a reporter PhoA lipoprotein was examined in M. gallisepticum. Mutation of the start codon from ATG to GTG resulted in a 2.5 fold reduction in the level of transcription of the phoA reporter, but the level of PhoA activity in the transformants containing phoA with a GTG start codon was only 63% of that of the transformants with a phoA with an ATG start codon, suggesting that GTG was a more efficient translational initiation codon. The effect of swapping the translational start codon in phoA reporter gene expression was less in M. gallisepticum than has been seen previously in Escherichia coli or Bacillus subtilis, suggesting the process of translational initiation in mycoplasmas may have some significant differences from those used in other bacteria. This is the first study of translational start codon usage in mycoplasmas and the impact of the use of an alternate start codon on expression in these bacteria. PMID:26010086

  1. Arginine (CGC) codon targeting in the human prostacyclin receptor gene (PTGIR) and G-protein coupled receptors (GPCR)

    PubMed Central

    Stitham, Jeremiah; Arehart, Eric J.; Gleim, Scott; Douville, Karen L.; MacKenzie, Todd; Hwa, John

    2007-01-01

    The human prostacyclin receptor (hIP) has recently been recognized as an important seven transmembrane G-protein coupled receptor that plays critical roles in a theroprevention and cardioprotection. To date, four non-synonymous genetic variants have been identified, two of which occur at the same Arg amino acid position (R212H, R212C). This observation instigated further genetic screening for prostacyclin receptor variants on 1,455 human genomic samples. A total of 31 distinct genetic variants were detected, with 6 (19%) involving Arg residues. Distinct differences in location and frequencies of genetic variants were noted between Caucasian, Asian, Hispanic and African Americans, with the most changes noted in the Asian cohort._From the sequencing results, three Arg-targeted changes at the same 212 position within the third cytoplasmic loop of the human prostacyclin (hIP) receptor were detected: 1) R212C (CGC→TGC), 2) R212H (CGC→CAC), and 3) R212R (CGC→CGT). Three additional Arg codon variants (all exhibiting the same CGC to TGC change) were also detected, R77C, R215C, and R279C. Analysis (GPCR and SNP databases) of 200 other GPCRs, with recorded non-synonymous mutations, confirmed a high frequency of Arg-targeted missense mutations, particularly within the important cytoplasmic domain. Preferential nucleotide changes (at Arg codons), were observed involving cytosine (C) to thymine (T) (pyrimidine to pyrimidine), as well as guanine (G) to adenine (A) (purine to purine) (p<0.001, Pearson’s goodness-of-fit test). Such targeting of Arg residues, leading to significant changes in coding amino acid size and/or charge, may have potentially-important structural and evolutionary implications on the hIP and GPCRs in general. In the case of the human prostacyclin receptor, such alterations may reduce the cardio-, vasculo-, and cytoprotective effects of prostacyclin. PMID:17481829

  2. Arginine (CGC) codon targeting in the human prostacyclin receptor gene (PTGIR) and G-protein coupled receptors (GPCR).

    PubMed

    Stitham, Jeremiah; Arehart, Eric J; Gleim, Scott; Douville, Karen; MacKenzie, Todd; Hwa, John

    2007-07-01

    The human prostacyclin receptor (hIP) has recently been recognized as an important seven transmembrane G-protein coupled receptor that plays critical roles in atheroprevention and cardioprotection. To date, four non-synonymous genetic variants have been identified, two of which occur at the same Arg amino acid position (R212H, R212C). This observation instigated further genetic screening for prostacyclin receptor variants on 1455 human genomic samples. A total of 31 distinct genetic variants were detected, with 6 (19%) involving Arg residues. Distinct differences in location and frequencies of genetic variants were noted between Caucasian, Asian, Hispanic and African Americans, with the most changes noted in the Asian cohort. From the sequencing results, three Arg-targeted changes at the same 212 position within the third cytoplasmic loop of the human prostacyclin (hIP) receptor were detected: 1) R212C (CGC-->TGC), 2) R212H (CGC-->CAC), and 3) R212R (CGC-->CGT). Three additional Arg codon variants (all exhibiting the same CGC to TGC change) were also detected, R77C, R215C, and R279C. Analysis (GPCR and SNP databases) of 200 other GPCRs, with recorded non-synonymous mutations, confirmed a high frequency of Arg-targeted missense mutations, particularly within the important cytoplasmic domain. Preferential nucleotide changes (at Arg codons), were observed involving cytosine (C) to thymine (T) (pyrimidine to pyrimidine), as well as guanine (G) to adenine (A) (purine to purine) (p<0.001, Pearson's goodness-of-fit test). Such targeting of Arg residues, leading to significant changes in coding amino acid size and/or charge, may have potentially-important structural and evolutionary implications on the hIP and GPCRs in general. In the case of the human prostacyclin receptor, such alterations may reduce the cardio-, vasculo-, and cytoprotective effects of prostacyclin. PMID:17481829

  3. Rosse, 3rd Earl of [William Parsons, Lord Rosse, Lord Oxmantown] (1800-67) and Rosse, 4th Earl of [Laurence Parsons, Lord Rosse, Lord Oxmantown] (1840-1908)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Irish astronomer and landowner, the 3rd Lord Rosse was educated at Trinity College, Dublin and Oxford as a mathematician. He became interested in astronomy and made at the family castle in Birr a 36 in reflector with the same design as William Herschel's (see HERSCEL FAMILY). Mapped the Moon, and observed nebulae with the intent to resolve them into stars. He developed the technology at Birr Cast...

  4. Image Quality of 3rd Generation Spiral Cranial Dual-Source CT in Combination with an Advanced Model Iterative Reconstruction Technique: A Prospective Intra-Individual Comparison Study to Standard Sequential Cranial CT Using Identical Radiation Dose

    PubMed Central

    Wenz, Holger; Maros, Máté E.; Meyer, Mathias; Förster, Alex; Haubenreisser, Holger; Kurth, Stefan; Schoenberg, Stefan O.; Flohr, Thomas; Leidecker, Christianne; Groden, Christoph; Scharf, Johann; Henzler, Thomas

    2015-01-01

    Objectives To prospectively intra-individually compare image quality of a 3rd generation Dual-Source-CT (DSCT) spiral cranial CT (cCT) to a sequential 4-slice Multi-Slice-CT (MSCT) while maintaining identical intra-individual radiation dose levels. Methods 35 patients, who had a non-contrast enhanced sequential cCT examination on a 4-slice MDCT within the past 12 months, underwent a spiral cCT scan on a 3rd generation DSCT. CTDIvol identical to initial 4-slice MDCT was applied. Data was reconstructed using filtered backward projection (FBP) and 3rd-generation iterative reconstruction (IR) algorithm at 5 different IR strength levels. Two neuroradiologists independently evaluated subjective image quality using a 4-point Likert-scale and objective image quality was assessed in white matter and nucleus caudatus with signal-to-noise ratios (SNR) being subsequently calculated. Results Subjective image quality of all spiral cCT datasets was rated significantly higher compared to the 4-slice MDCT sequential acquisitions (p<0.05). Mean SNR was significantly higher in all spiral compared to sequential cCT datasets with mean SNR improvement of 61.65% (p*Bonferroni0.05<0.0024). Subjective image quality improved with increasing IR levels. Conclusion Combination of 3rd-generation DSCT spiral cCT with an advanced model IR technique significantly improves subjective and objective image quality compared to a standard sequential cCT acquisition acquired at identical dose levels. PMID:26288186

  5. Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins

    NASA Astrophysics Data System (ADS)

    Tang, Nicholas C.; Chilkoti, Ashutosh

    2016-04-01

    Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

  6. Codon-optimized antibiotic resistance gene improves efficiency of transient transformation in Frankia.

    PubMed

    Kucho, Ken-Ichi; Kakoi, Kentaro; Yamaura, Masatoshi; Iwashita, Mari; Abe, Mikiko; Uchiumi, Toshiki

    2013-11-01

    Frankia is a unique actinobacterium having abilities to fix atmospheric dinitrogen and to establish endosymbiosis with trees, but molecular bases underlying these interesting characteristics are poorly understood because of a lack of stable transformation system. Extremely high GC content of Frankia genome (more than 70 percent) can be a hindrance to successful transformation. We generated a synthetic gentamicin resistance gene whose codon usage is optimized to Frankia (fgmR) and evaluated its usefulness as a selection marker using a transient transformation system. Success rate of transient transformation and cell growth in selective culture were significantly increased by use of fgmR instead of a native gentamicin resistance gene, suggesting that codon optimization improved translation efficiency of the marker gene and increased antibiotic resistance. Our result shows that similarity in codon usage pattern is an important factor to be taken into account when exogenous transgenes are expressed in Frankia cells. PMID:24287650

  7. Effects of Deep Water Source-Sink Terms in 3rd generation Wave Model SWAN using different wind data in Black Sea

    NASA Astrophysics Data System (ADS)

    Kirezci, Cagil; Ozyurt Tarakcioglu, Gulizar

    2016-04-01

    Coastal development in Black Sea has increased in recent years. Therefore, careful monitoring of the storms and verification of numerical tools with reliable data has become important. Previous studies by Kirezci and Ozyurt (2015) investigated extreme events in Black Sea using different wind datasets (NCEP's CFSR and ECMWF's operational datasets) and different numerical tools (SWAN and Wavewatch III). These studies showed that significant effect to results is caused by the deep water source-sink terms (wave growth by wind, deep water dissipation of wave energy (whitecapping) and deep water non-linear wave-wave interactions). According to Timmermans(2015), uncertainty about wind forcing and the process of nonlinear wave-wave interactions are found to be dominant in numerical wave modelling. Therefore, in this study deep water source and sink term solution approaches of 3rd generation numerical tool (SWAN model) are tested, validated and compared using the selected extreme storms in Black Sea. 45 different storms and storm like events observed in Black Sea between years 1994-1999 are selected to use in the models. The storm selection depends on the instrumental wave data (significant wave heights, mean wave period and mean wave direction) obtained in NATO-TU Waves project by the deep water buoy measurements at Hopa, Sinop, Gelendzhik, and wind data (mean and peak wind speeds, storm durations) of the regarding events. 2 different wave growth by wind with the corresponding deep water dissipation terms and 3 different wave -wave interaction terms of SWAN model are used in this study. Wave growth by wind consist of two parts, linear growth which is explained by Cavaleri and Malanotte-Rizzoli(1981),and dominant exponential growth. There are two methods in SWAN model for exponential growth of wave, first one by Snyder et al. (1981), rescaled in terms of friction velocity by Komen et. al (1984) which is derived using driving wind speed at 10m elevation with related drag

  8. Effects of Deep Water Source-Sink Terms in 3rd generation Wave Model SWAN using different wind data in Black Sea

    NASA Astrophysics Data System (ADS)

    Kirezci, Cagil; Ozyurt Tarakcioglu, Gulizar

    2016-04-01

    Coastal development in Black Sea has increased in recent years. Therefore, careful monitoring of the storms and verification of numerical tools with reliable data has become important. Previous studies by Kirezci and Ozyurt (2015) investigated extreme events in Black Sea using different wind datasets (NCEP's CFSR and ECMWF's operational datasets) and different numerical tools (SWAN and Wavewatch III). These studies showed that significant effect to results is caused by the deep water source-sink terms (wave growth by wind, deep water dissipation of wave energy (whitecapping) and deep water non-linear wave-wave interactions). According to Timmermans(2015), uncertainty about wind forcing and the process of nonlinear wave-wave interactions are found to be dominant in numerical wave modelling. Therefore, in this study deep water source and sink term solution approaches of 3rd generation numerical tool (SWAN model) are tested, validated and compared using the selected extreme storms in Black Sea. 45 different storms and storm like events observed in Black Sea between years 1994-1999 are selected to use in the models. The storm selection depends on the instrumental wave data (significant wave heights, mean wave period and mean wave direction) obtained in NATO-TU Waves project by the deep water buoy measurements at Hopa, Sinop, Gelendzhik, and wind data (mean and peak wind speeds, storm durations) of the regarding events. 2 different wave growth by wind with the corresponding deep water dissipation terms and 3 different wave -wave interaction terms of SWAN model are used in this study. Wave growth by wind consist of two parts, linear growth which is explained by Cavaleri and Malanotte-Rizzoli(1981),and dominant exponential growth. There are two methods in SWAN model for exponential growth of wave, first one by Snyder et al. (1981), rescaled in terms of friction velocity by Komen et. al (1984) which is derived using driving wind speed at 10m elevation with related drag

  9. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli

    PubMed Central

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

  10. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli.

    PubMed

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

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

    PubMed Central

    Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas; Igarashi, Takao; Cohen, Lydia; Hou, Ya-Ming; Jensen, Lars Juhl

    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 at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins. PMID:22373820

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

    ERIC Educational Resources Information Center

    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…

  13. Effective population size does not predict codon usage bias in mammals

    PubMed Central

    Kessler, Michael D; Dean, Matthew D

    2014-01-01

    Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (Ne), with selection on CUB operating less efficiently in species with small Ne. Here, we specifically ask whether variation in Ne predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of Ne (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X-linked genes, and high-recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in Ne predicts variation in CUB. Second, across six mammalian species with genetic estimates of Ne (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), Ne and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in Ne does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between Ne and CUB. PMID:25505518

  14. Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish.

    PubMed

    Mishima, Yuichiro; Tomari, Yukihide

    2016-03-17

    The control of mRNA stability plays a central role in regulating gene expression. In metazoans, the earliest stages of development are driven by maternally supplied mRNAs. The degradation of these maternal mRNAs is critical for promoting the maternal-to-zygotic transition of developmental programs, although the underlying mechanisms are poorly understood in vertebrates. Here, we characterized maternal mRNA degradation pathways in zebrafish using a transcriptome analysis and systematic reporter assays. Our data demonstrate that ORFs enriched with uncommon codons promote deadenylation by the CCR4-NOT complex in a translation-dependent manner. This codon-mediated mRNA decay is conditional on the context of the 3' UTR, with long 3' UTRs conferring resistance to deadenylation. These results indicate that the combined effect of codon usage and 3' UTR length determines the stability of maternal mRNAs in zebrafish embryos. Our study thus highlights the codon-mediated mRNA decay as a conserved regulatory mechanism in eukaryotes. PMID:26990990

  15. Conservation of CFTR codon frequency through primates suggests synonymous mutations could have a functional effect.

    PubMed

    Pizzo, Lucilla; Iriarte, Andrés; Alvarez-Valin, Fernando; Marín, Mónica

    2015-05-01

    Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease. PMID:25839760

  16. Effective population size does not predict codon usage bias in mammals.

    PubMed

    Kessler, Michael D; Dean, Matthew D

    2014-10-01

    Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (N e), with selection on CUB operating less efficiently in species with small N e. Here, we specifically ask whether variation in N e predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of N e (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X-linked genes, and high-recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in N e predicts variation in CUB. Second, across six mammalian species with genetic estimates of N e (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), N e and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in N e does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between N e and CUB. PMID:25505518

  17. Genetic analysis of diversity within a Chinese local sugarcane germplasm based on start codon targeted polymorphism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic dive...

  18. Partitioning between recoding and termination at a stop codon-selenocysteine insertion sequence.

    PubMed

    Kotini, Suresh Babu; Peske, Frank; Rodnina, Marina V

    2015-07-27

    Selenocysteine (Sec) is inserted into proteins by recoding a UGA stop codon followed by a selenocysteine insertion sequence (SECIS). UGA recoding by the Sec machinery is believed to be very inefficient owing to RF2-mediated termination at UGA. Here we show that recoding efficiency in vivo is 30-40% independently of the cell growth rate. Efficient recoding requires sufficient selenium concentrations in the medium. RF2 is an unexpectedly poor competitor of Sec. We recapitulate the major characteristics of SECIS-dependent UGA recoding in vitro using a fragment of fdhF-mRNA encoding a natural bacterial selenoprotein. Only 40% of actively translating ribosomes that reach the UGA codon insert Sec, even in the absence of RF2, suggesting that the capacity to insert Sec into proteins is inherently limited. RF2 does not compete with the Sec incorporation machinery; rather, it terminates translation on those ribosomes that failed to incorporate Sec. The data suggest a model in which early recruitment of Sec-tRNA(Sec)-SelB-GTP to the SECIS blocks the access of RF2 to the stop codon, thereby prioritizing recoding over termination at Sec-dedicated stop codons. PMID:26040702

  19. Genetic diversity of mango cultivars estimated using Start Codon Targeted (SCoT) markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diversity and genetic relationships among 23 mango germplasm accessions, collected from different locations in Guangxi province in China, were analyzed by using a novel and simple gene targeted DNA marker: Start Codon Targeted (SCoT) markers. This technique uses a single, 18-mer primer PCR amplifica...

  20. Effects of codon modification on human BMP2 gene expression in tobacco plants.

    PubMed

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Duan, Ziyuan; He, Zhengquan; Yao, Wei; Yue, Chaoyin; Dai, Jianwu

    2006-07-01

    Bone morphogenetic protein 2 (BMP2) has great potential in therapeutic applications. We are working on generating transgenic plants as a bioreactor to produce BMP2. We have studied the effects of codon optimization on the expression of human BMP2 (hBMP2) in tobacco plants. Three modified hBMP2 genes were transformed into tobacco under the control of either cauliflower mosaic virus 35S (CaMV35S) promoter or double-CaMV35S promoter plus alfalfa mosaic virus (AMV) enhancer. The fused beta-glucuronidase (GUS) reporter gene was used to facilitate the assay of protein expression. The results indicated that codon optimization could increase the protein expression level obviously under CaMV35S promoter. However, under relatively stronger initiation condition (double-CaMV35S promoter plus AMV enhancer), only the gene with the lowest degree of codon optimization could increase the protein expression level. Our findings suggest that the action of codon optimization may be influenced by the factors of promoter strength and A+T content in tobacco plants. PMID:16491379

  1. Solving the riddle of codon usage preferences: a test for translational selection

    PubMed Central

    Reis, Mario dos; Savva, Renos; Wernisch, Lorenz

    2004-01-01

    Translational selection is responsible for the unequal usage of synonymous codons in protein coding genes in a wide variety of organisms. It is one of the most subtle and pervasive forces of molecular evolution, yet, establishing the underlying causes for its idiosyncratic behaviour across living kingdoms has proven elusive to researchers over the past 20 years. In this study, a statistical model for measuring translational selection in any given genome is developed, and the test is applied to 126 fully sequenced genomes, ranging from archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are interacting forces that ultimately determine the action of translational selection, and that an optimal genome size exists for which this kind of selection is maximal. Accordingly, genome size also presents upper and lower boundaries beyond which selection on codon usage is not possible. We propose a model where the coevolution of genome size and tRNA genes explains the observed patterns in translational selection in all living organisms. This model finally unifies our understanding of codon usage across prokaryotes and eukaryotes. Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage paradigms that can be better understood under the proposed model. PMID:15448185

  2. Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome

    PubMed Central

    Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

    2009-01-01

    We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest. PMID:19131380

  3. Influenza A Virus Attenuation by Codon Deoptimization of the NS Gene for Vaccine Development

    PubMed Central

    Nogales, Aitor; Baker, Steven F.; Ortiz-Riaño, Emilio; Dewhurst, Stephen; Topham, David J.

    2014-01-01

    ABSTRACT Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential. Considering that most amino acids can be synthesized from several synonymous codons, this study employed the use of misrepresented mammalian codons (codon deoptimization) for the de novo synthesis of a viral NS RNA segment based on influenza A/Puerto Rico/8/1934 (H1N1) (PR8) virus. We generated three different recombinant influenza PR8 viruses containing codon-deoptimized synonymous mutations in coding regions comprising the entire NS gene or the mRNA corresponding to the individual viral protein NS1 or NEP, without modifying the respective splicing and packaging signals of the viral segment. The fitness of these synthetic viruses was attenuated in vivo, while they retained immunogenicity, conferring both homologous and heterologous protection against influenza A virus challenges. These results indicate that influenza viruses can be effectively attenuated by synonymous codon deoptimization of the NS gene and open the possibility of their use as a safe vaccine to prevent infections with these important human pathogens. IMPORTANCE Vaccination serves as the best therapeutic option to protect humans against influenza viral infections. However, the efficacy of current influenza vaccines is suboptimal, and novel approaches are necessary for the prevention of disease cause by this important human respiratory pathogen. The nonstructural

  4. 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

    SciTech Connect

    Bonaventure, J.; Lasselin, C.; Toutain, A.

    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.

  5. Codon reassignment to facilitate genetic engineering and biocontainment in the chloroplast of Chlamydomonas reinhardtii.

    PubMed

    Young, Rosanna E B; Purton, Saul

    2016-05-01

    There is a growing interest in the use of microalgae as low-cost hosts for the synthesis of recombinant products such as therapeutic proteins and bioactive metabolites. In particular, the chloroplast, with its small, genetically tractable genome (plastome) and elaborate metabolism, represents an attractive platform for genetic engineering. In Chlamydomonas reinhardtii, none of the 69 protein-coding genes in the plastome uses the stop codon UGA, therefore this spare codon can be exploited as a useful synthetic biology tool. Here, we report the assignment of the codon to one for tryptophan and show that this can be used as an effective strategy for addressing a key problem in chloroplast engineering: namely, the assembly of expression cassettes in Escherichia coli when the gene product is toxic to the bacterium. This problem arises because the prokaryotic nature of chloroplast promoters and ribosome-binding sites used in such cassettes often results in transgene expression in E. coli, and is a potential issue when cloning genes for metabolic enzymes, antibacterial proteins and integral membrane proteins. We show that replacement of tryptophan codons with the spare codon (UGG→UGA) within a transgene prevents functional expression in E. coli and in the chloroplast, and that co-introduction of a plastidial trnW gene carrying a modified anticodon restores function only in the latter by allowing UGA readthrough. We demonstrate the utility of this system by expressing two genes known to be highly toxic to E. coli and discuss its value in providing an enhanced level of biocontainment for transplastomic microalgae. PMID:26471875

  6. Relationship between codon biased genes, microarray expression values and physiological characteristics of Streptococcus pneumoniae.

    PubMed

    Martín-Galiano, Antonio J; Wells, Jerry M; de la Campa, Adela G

    2004-07-01

    A codon-profile strategy was used to predict gene expression levels in Streptococcus pneumoniae. Predicted highly expressed (PHE) genes included those encoding glycolytic and fermentative enzymes, sugar-conversion systems and carbohydrate-transporters. Additionally, some genes required for infection that are involved in oxidative metabolism and hydrogen peroxide production were PHE. Low expression values were predicted for genes encoding specific regulatory proteins like two-component systems and competence genes. Correspondence analysis localized 484 ORFs which shared a distinctive codon profile in the right horn. These genes had a mean G+C content (33.4 %) that was lower than the bulk of the genome coding sequences (39.7 %), suggesting that many of them were acquired by horizontal transfer. Half of these genes (242) were pseudogenes, ORFs shorter than 80 codons or without assigned function. The remaining genes included several virulence factors, such as capsular genes, iga, lytB, nanB, pspA, choline-binding proteins, and functions related to DNA acquisition, such as restriction-modification systems and comDE. In order to compare predicted translation rate with the relative amounts of mRNA for each gene, the codon adaptation index (CAI) values were compared with microarray fluorescence intensity values following hybridization of labelled RNA from laboratory-grown cultures. High mRNA amounts were observed in 32.5 % of PHE genes and in 64 % of the 25 genes with the highest CAI values. However, high relative amounts of RNA were also detected in 10.4 % of non-PHE genes, such as those encoding fatty acid metabolism enzymes and proteases, suggesting that their expression might also be regulated at the level of transcription or mRNA stability under the conditions tested. The effects of codon bias and mRNA amount on different gene groups in S. pneumoniae are discussed. PMID:15256573

  7. Association between p53 polymorphism at codon 72 and recurrent spontaneous abortion.

    PubMed

    Zhang, Ying; Wu, Yuan-Yuan; Qiao, Fu-Yuan; Zeng, Wan-Jiang

    2016-06-01

    p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine (Arg) to a proline (Pro) at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion (RSA). In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium (HWE). There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model (Pro/Pro vs. Pro/Arg+Arg/Arg; OR=1.60, 95% CI: 1.14-2.24) and co-dominant model (Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI: 1.02-2.12) whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model (Pro vs. Arg; OR=1.28, 95% CI: 1.04-1.57) after exclusion of the study that was deviated from HWE. No association was noted in recessive model (Pro/Pro+Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI: 0.86-1.30) and co-dominant model (Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI: 0.77-1.19). Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA. PMID:27376811

  8. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species.

    PubMed

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-09-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3 This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

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

    PubMed Central

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

    2009-01-01

    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 assembly procedure with mis

  10. Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

    PubMed Central

    Miyazawa, Sanzo

    2011-01-01

    Background Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Results Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. Conclusions/Significance The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences. PMID:21445250

  11. Structural characterization of eRF1 mutants indicate a complex mechanism of stop codon recognition.

    PubMed

    Pillay, Shubhadra; Li, Yan; Wong, Leo E; Pervushin, Konstantin

    2016-01-01

    Eukarya translation termination requires the stop codon recognizing protein eRF1. In contrast to the multiple proteins required for translation termination in Bacteria, eRF1 retains the ability to recognize all three of the stop codons. The details of the mechanism that eRF1 uses to recognize stop codons has remained elusive. This study describes the structural effects of mutations in the eRF1 N-domain that have previously been shown to alter stop codon recognition specificity. Here, we propose a model of eRF1 binding to the pre-translation termination ribosomal complex that is based in part on our solution NMR structures of the wild-type and mutant eRF1 N-domains. Since structural perturbations induced by these mutations were spread throughout the protein structure, residual dipolar coupling (RDC) data were recorded to establish the long-range effects of the specific mutations, E55Q, Y125F, Q(122)FM(Y)F(126). RDCs were recorded on (15)N-labeled eRF1 N-domain weakly aligned in either 5% w/v n-octyl-penta (ethylene glycol)/octanol (C8E5) or the filamentous phage Pf1. These data indicate that the mutations alter the conformation and dynamics of the GTS loop that is distant from the mutation sites. We propose that the GTS loop forms a switch that is key for the multiple codon recognition capability of eRF1. PMID:26725946

  12. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species

    PubMed Central

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-01-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3. This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

  13. Structural characterization of eRF1 mutants indicate a complex mechanism of stop codon recognition

    PubMed Central

    Pillay, Shubhadra; Li, Yan; Wong, Leo E; Pervushin, Konstantin

    2016-01-01

    Eukarya translation termination requires the stop codon recognizing protein eRF1. In contrast to the multiple proteins required for translation termination in Bacteria, eRF1 retains the ability to recognize all three of the stop codons. The details of the mechanism that eRF1 uses to recognize stop codons has remained elusive. This study describes the structural effects of mutations in the eRF1 N-domain that have previously been shown to alter stop codon recognition specificity. Here, we propose a model of eRF1 binding to the pre-translation termination ribosomal complex that is based in part on our solution NMR structures of the wild-type and mutant eRF1 N-domains. Since structural perturbations induced by these mutations were spread throughout the protein structure, residual dipolar coupling (RDC) data were recorded to establish the long-range effects of the specific mutations, E55Q, Y125F, Q122FM(Y)F126. RDCs were recorded on 15N-labeled eRF1 N-domain weakly aligned in either 5% w/v n-octyl-penta (ethylene glycol)/octanol (C8E5) or the filamentous phage Pf1. These data indicate that the mutations alter the conformation and dynamics of the GTS loop that is distant from the mutation sites. We propose that the GTS loop forms a switch that is key for the multiple codon recognition capability of eRF1. PMID:26725946

  14. The ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24-25, 2015. Workshop Report.

    PubMed

    Kager, Leo; Whelan, Jeremy; Dirksen, Uta; Hassan, Bass; Anninga, Jakob; Bennister, Lindsey; Bovée, Judith V M G; Brennan, Bernadette; Broto, Javier M; Brugières, Laurence; Cleton-Jansen, Anne-Marie; Copland, Christopher; Dutour, Aurélie; Fagioli, Franca; Ferrari, Stefano; Fiocco, Marta; Fleuren, Emmy; Gaspar, Nathalie; Gelderblom, Hans; Gerrand, Craig; Gerß, Joachim; Gonzato, Ornella; van der Graaf, Winette; Hecker-Nolting, Stefanie; Herrero-Martín, David; Klco-Brosius, Stephanie; Kovar, Heinrich; Ladenstein, Ruth; Lancia, Carlo; LeDeley, Marie-Cecile; McCabe, Martin G; Metzler, Markus; Myklebost, Ola; Nathrath, Michaela; Picci, Piero; Potratz, Jenny; Redini, Françoise; Richter, Günther H S; Reinke, Denise; Rutkowski, Piotr; Scotlandi, Katia; Strauss, Sandra; Thomas, David; Tirado, Oscar M; Tirode, Franck; Vassal, Gilles; Bielack, Stefan S

    2016-01-01

    This report summarizes the results of the 3rd Joint ENCCA-WP7, EuroSarc, EEC, PROVABES, and EURAMOS European Bone Sarcoma Network Meeting, which was held at the Children's Cancer Research Institute in Vienna, Austria on September 24-25, 2015. The joint bone sarcoma network meetings bring together European bone sarcoma researchers to present and discuss current knowledge on bone sarcoma biology, genetics, immunology, as well as results from preclinical investigations and clinical trials, to generate novel hypotheses for collaborative biological and clinical investigations. The ultimate goal is to further improve therapy and outcome in patients with bone sarcomas. PMID:27315524

  15. Increased rate of depression and psychosomatic symptoms in Jewish migrants from the post-Soviet-Union to Germany in the 3rd generation after the Shoa.

    PubMed

    Ullmann, E; Barthel, A; Licinio, J; Petrowski, K; Bornstein, S R; Strauß, B

    2013-01-01

    The mental health status of persons with Jewish background living in Germany is discussed with special regard to social exclusion like anti-Semitism and overprotective parental rearing behavior, as a transmissional factor of the KZ-Syndrome. These stressors are considered in the context of a higher risk for depression/fear and psychosomatic disorders and also abnormal cortisol levels. The present sample (N=89) is derived from the Jewish population currently living in the German region of Saxony aged between 17-36 years that emigrated from the post-Soviet-Union areas. The mean age was 22.9 years. Two questionnaires to detect psychosomatic symptoms (Giessen complaint list (GBB)-24, hospital anxiety and depression scale) and one questionnaire addressing parental rearing behavior (FEE) were employed. Comparisons were drawn with normative data from the literature about the German residential population. In addition, questions were asked concerning the experience of anti-Semitism in Germany and in the post-Soviet-Union areas. A higher prevalence of depression/fear (10.3% versus 18.2%) and psychosomatic symptoms (M=14.03 versus 17.8; t=2.42; P<0.05) was observed in Jewish migrants to Germany as compared with non-Jewish German residents. Furthermore, anti-Semitic experiences in Germany correlated positively with depression (r=0.293; P<0.01) and fear (r=0.254; P<0.05). The anti-Semitic experiences in the post-Soviet-Union areas also correlated positively with limb pain (r=0.41, P<0.01), fatigue symptoms (r=0.296, P<0.01) and psychocardial symptoms (r=0.219, P<0.05). It was also confirmed that the male respondents recalled a controlling and overprotecting maternal rearing behavior more frequently than the German standard random sample (M=15.39 versus 18.6; t=2.68; P<0.01). The latter also correlated significantly positive with epigastric pain (r=0.349; P<0.01). The present results show that depression, fear and psychosomatic problems are common in Jewish residents with a

  16. JCat: a novel tool to adapt codon usage of a target gene to its potential expression host.

    PubMed

    Grote, Andreas; Hiller, Karsten; Scheer, Maurice; Münch, Richard; Nörtemann, Bernd; Hempel, Dietmar C; Jahn, Dieter

    2005-07-01

    A novel method for the adaptation of target gene codon usage to most sequenced prokaryotes and selected eukaryotic gene expression hosts was developed to improve heterologous protein production. In contrast to existing tools, JCat (Java Codon Adaptation Tool) does not require the manual definition of highly expressed genes and is, therefore, a very rapid and easy method. Further options of JCat for codon adaptation include the avoidance of unwanted cleavage sites for restriction enzymes and Rho-independent transcription terminators. The output of JCat is both graphically and as Codon Adaptation Index (CAI) values given for the pasted sequence and the newly adapted sequence. Additionally, a list of genes in FASTA-format can be uploaded to calculate CAI values. In one example, all genes of the genome of Caenorhabditis elegans were adapted to Escherichia coli codon usage and further optimized to avoid commonly used restriction sites. In a second example, the Pseudomonas aeruginosa exbD gene codon usage was adapted to E.coli codon usage with parallel avoidance of the same restriction sites. For both, the degree of introduced changes was documented and evaluated. JCat is integrated into the PRODORIC database that hosts all required information on the various organisms to fulfill the requested calculations. JCat is freely accessible at http://www.prodoric.de/JCat. PMID:15980527

  17. Improving the efficiency of the genetic code by varying the codon length--the perfect genetic code.

    PubMed

    Doig, A J

    1997-10-01

    The function of DNA is to specify protein sequences. The four-base "alphabet" used in nucleic acids is translated to the 20 base alphabet of proteins (plus a stop signal) via the genetic code. The code is neither overlapping nor punctuated, but has mRNA sequences read in successive triplet codons until reaching a stop codon. The true genetic code uses three bases for every amino acid. The efficiency of the genetic code can be significantly increased if the requirement for a fixed codon length is dropped so that the more common amino acids have shorter codon lengths and rare amino acids have longer codon lengths. More efficient codes can be derived using the Shannon-Fano and Huffman coding algorithms. The compression achieved using a Huffman code cannot be improved upon. I have used these algorithms to derive efficient codes for representing protein sequences using both two and four bases. The length of DNA required to specify the complete set of protein sequences could be significantly shorter if transcription used a variable codon length. The restriction to a fixed codon length of three bases means that it takes 42% more DNA than the minimum necessary, and the genetic code is 70% efficient. One can think of many reasons why this maximally efficient code has not evolved: there is very little redundancy so almost any mutation causes an amino acid change. Many mutations will be potentially lethal frame-shift mutations, if the mutation leads to a change in codon length. It would be more difficult for the machinery of transcription to cope with a variable codon length. Nevertheless, in the strict and narrow sense of coding for protein sequences using the minimum length of DNA possible, the Huffman code derived here is perfect. PMID:9344740

  18. [Bacteriological studies of travellar's diarrhoea. 5) Analysis of enteropathogenic bacteria at Osaka Airport Quarantine Station from January 1992 through September 3rd, 1994].

    PubMed

    Ueda, Y; Suzuki, N; Mori, H; Miyagi, K; Noda, K; Hirose, H; Takegaki, Y; Hashimoto, S; Oosumi, Y; Miyata, Y; Taguchi, M; Ishibashi, M; Honda, T

    1996-01-01

    . paraemolyticus. 87.4% of all V. parahaemolyticus strains were positive with thermostable direct hemolysin (TDH) gene, and 12.6% of them were positive with TDH-related hemolysin (TRH) gene by DNA-probe methods. PMID:8822051

  19. Mutation at embB codon 306, a potential marker for the identification of multidrug resistance associated with ethambutol in Mycobacterium tuberculosis.

    PubMed

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael; Zenteno-Cuevas, Roberto

    2015-09-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMB(r)), 49 were sensitive to ethambutol (EMB(s)) but were resistant to another drug, and 65 were pansensitive isolates (P(s)). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the P(s) isolates (1/65), one of the EMB(s) isolates (1/49), and 20 of the EMB(r) isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs. PMID:26124153

  20. Mutation at embB Codon 306, a Potential Marker for the Identification of Multidrug Resistance Associated with Ethambutol in Mycobacterium tuberculosis

    PubMed Central

    Cuevas-Córdoba, Betzaida; Juárez-Eusebio, Dulce María; Almaraz-Velasco, Raquel; Muñiz-Salazar, Raquel; Laniado-Laborin, Rafael

    2015-01-01

    Ethambutol inhibits arabinogalactan and lipoarabinomannan biosynthesis in mycobacteria. The occurrence of mutations in embB codon 306 in ethambutol-susceptible isolates and their absence in resistant isolates has raised questions regarding the utility of this codon as a potential marker for resistance against ethambutol. The characterization of mutations on embB 306 will contribute to a better understanding of the mechanisms of resistance to this drug; therefore, the purpose of this study was to investigate the association between embB 306 mutations and first-line drug resistance profiles in tuberculosis isolates. We sequenced the region surrounding the embB 306 codon in 175 tuberculosis clinical isolates, divided according to drug sensitivity, in three groups: 110 were resistant to at least one first-line drug, of which 61 were resistant to ethambutol (EMBr), 49 were sensitive to ethambutol (EMBs) but were resistant to another drug, and 65 were pansensitive isolates (Ps). The associations between embB 306 mutations and phenotypic resistance to all first-line drugs were determined, and their validity and safety as a diagnostic marker were assessed. One of the Ps isolates (1/65), one of the EMBs isolates (1/49), and 20 of the EMBr isolates (20/61) presented with an embB 306 mutation. Four different single-nucleotide polymorphisms (SNPs) at embB 306 were associated with simultaneous resistance to ethambutol, isoniazid, and rifampin (odds ratio [OR], 17.7; confidence interval [CI], 5.6 to 56.1) and showed a positive predictive value of 82%, with a specificity of 97% for diagnosing multidrug resistance associated with ethambutol, indicating its potential as a molecular marker for several drugs. PMID:26124153

  1. Gene Expression Levels Are Correlated with Synonymous Codon Usage, Amino Acid Composition, and Gene Architecture in the Red Flour Beetle, Tribolium castaneum

    PubMed Central

    Williford, Anna; Demuth, Jeffery P.

    2012-01-01

    Gene expression levels correlate with multiple aspects of gene sequence and gene structure in phylogenetically diverse taxa, suggesting an important role of gene expression levels in the evolution of protein-coding genes. Here we present results of a genome-wide study of the influence of gene expression on synonymous codon usage, amino acid composition, and gene structure in the red flour beetle, Tribolium castaneum. Consistent with the action of translational selection, we find that synonymous codon usage bias increases with gene expression. However, the correspondence between tRNA gene copy number and optimal codons is weak. At the amino acid level, translational selection is suggested by the positive correlation between tRNA gene numbers and amino acid usage, which is stronger for highly expressed genes. In addition, there is a clear trend for increased use of metabolically cheaper, less complex amino acids as gene expression increases. tRNA gene numbers also correlate negatively with amino acid size/complexity (S/C) score indicating the coupling between translational selection and selection to minimize the use of large/complex amino acids. Interestingly, the analysis of 10 additional genomes suggests that the correlation between tRNA gene numbers and amino acid S/C score is widespread and might be explained by selection against negative consequences of protein misfolding. At the level of gene structure, three major trends are detected: 1) complete coding region length increases across low and intermediate expression levels but decreases in highly expressed genes; 2) the average intron size shows the opposite trend, first decreasing with expression, followed by a slight increase in highly expressed genes; and 3) intron density remains nearly constant across all expression levels. These changes in gene architecture are only in partial agreement with selection favoring reduced cost of biosynthesis. PMID:22826459

  2. Itaconic acid production from glycerol using Escherichia coli harboring a random synonymous codon-substituted 5'-coding region variant of the cadA gene.

    PubMed

    Jeon, Ho-Geun; Cheong, Dae-Eun; Han, Yunjon; Song, Jae Jun; Choi, Jong Hyun

    2016-07-01

    Aspergillus terreus cadA, encoding cis-aconitate decarboxylase, is an essential gene for itaconic acid (IA) biosynthesis, but it is primarily expressed as insoluble aggregates in most industrial hosts. This has been a hurdle for the development of recombinant strategies for IA production. Here, we created a library of synonymous codon variants (scv) of the cadA gene containing synonymous codons in the first 10 codons (except ATG) and screened it in Escherichia coli. Among positive clones, E. coli scvCadA_No8 showed more than 95% of expressed CadA in the soluble fraction, and in production runs, produced threefold more IA than wild-type E. coli in Luria-Bertani broth supplemented with 0.5% glucose. In M9 minimal media containing 0.85 g/L citrate and 1% glycerol, E. coli scvCadA_No8 produced 985.6 ± 33.4 mg/L IA during a 72-h culture after induction with isopropyl β-D-1-thiogalactopyranoside. In a 2-L fed-batch fermentation consisting of two stages (growth and nitrogen limitation conditions), we obtained 7.2 g/L IA by using E. coli by introducing only the scv_cadA gene and optimizing culture conditions for IA production. These results could be combined with metabolic engineering and generate an E. coli strain as an industrial IA producer. Biotechnol. Bioeng. 2016;113: 1504-1510. © 2015 Wiley Periodicals, Inc. PMID:26704570

  3. Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions

    PubMed Central

    Zoller, Stefan; Boskova, Veronika; Anisimova, Maria

    2015-01-01

    Many protein sequences have distinct domains that evolve with different rates, different selective pressures, or may differ in codon bias. Instead of modeling these differences by more and more complex models of molecular evolution, we present a multipartition approach that allows maximum-likelihood phylogeny inference using different codon models at predefined partitions in the data. Partition models can, but do not have to, share free parameters in the estimation process. We test this approach with simulated data as well as in a phylogenetic study of the origin of the leucin-rich repeat regions in the type III effector proteins of the pythopathogenic bacteria Ralstonia solanacearum. Our study does not only show that a simple two-partition model resolves the phylogeny better than a one-partition model but also gives more evidence supporting the hypothesis of lateral gene transfer events between the bacterial pathogens and its eukaryotic hosts. PMID:25911229

  4. Big Data, Evolution, and Metagenomes: Predicting Disease from Gut Microbiota Codon Usage Profiles.

    PubMed

    Fabijanić, Maja; Vlahoviček, Kristian

    2016-01-01

    Metagenomics projects use next-generation sequencing to unravel genetic potential in microbial communities from a wealth of environmental niches, including those associated with human body and relevant to human health. In order to understand large datasets collected in metagenomics surveys and interpret them in context of how a community metabolism as a whole adapts and interacts with the environment, it is necessary to extend beyond the conventional approaches of decomposing metagenomes into microbial species' constituents and performing analysis on separate components. By applying concepts of translational optimization through codon usage adaptation on entire metagenomic datasets, we demonstrate that a bias in codon usage present throughout the entire microbial community can be used as a powerful analytical tool to predict for community lifestyle-specific metabolism. Here we demonstrate this approach combined with machine learning, to classify human gut microbiome samples according to the pathological condition diagnosed in the human host. PMID:27115650

  5. Lack of IRS-1 codon 513 and 972 polymorphism in Pima Indians

    SciTech Connect

    Celi, F.S.; Silver, K.; Walston, J.

    1995-09-01

    Insulin receptor substrate-1 (IRS-1), a 1242 amino acid protein, an endogenous substrate for the insulin receptor tyrosine kinase, mediates many or all of the metabolic actions of insulin. Recently, polymorphism at codons 513 and 972 of the IRS-1 gene resulting in 2 amino acid substitutions that were associated with type II diabetes were found in a Caucasian population. Using allele specific oligonucleotide (ASO) hybridization, we screened 242 diabetic and 190 nondiabetic Pima Indians, a population with a very high prevalence of type II diabetes. Neither of the two mutations was present in either diabetic or nondiabetic subjects. We conclude that polymorphism at codons 513 and 972 of the IRS-1 gene observed in certain Caucasian populations is very rare or absent in Pima Indians. 20 refs., 2 figs., 1 tab.

  6. A POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY

    PubMed Central

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A.; Dell’Osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

    2011-01-01

    SUMMARY Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behavior. The complex origins of impulsivity hinder identification of the genes influencing both it and diseases with which it is associated. We performed exon-centric sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B that is common (MAF >1%) but exclusive to Finns was identified. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon that was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviors in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioral phenotypes using founder populations, and suggests a role for HTR2B in impulsivity. PMID:21179162

  7. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma.

    PubMed

    Harbour, J William; Roberson, Elisha D O; Anbunathan, Hima; Onken, Michael D; Worley, Lori A; Bowcock, Anne M

    2013-02-01

    Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

  8. Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers.

    PubMed

    Kang, Mi Ran; Kim, Min Sung; Oh, Ji Eun; Kim, Yoo Ri; Song, Sang Yong; Seo, Seong Il; Lee, Ji Youl; Yoo, Nam Jin; Lee, Sug Hyung

    2009-07-15

    Missense somatic mutations in IDH1 gene affecting codon 132 have recently been reported in glioblastoma multiforme (GBM) and other gliomas. The recurrent nature of the IDH1 mutations in the same amino acid strongly suggests that the mutations may play important roles in the pathogenesis of glial tumors. The aim of this study was to see whether the IDH1 codon 132 mutations occur in other human cancers besides glial tumors. We also attempted to confirm the occurrence of the IDH1 mutations in GBM of Korean patients. We have analyzed 1,186 cancer tissues from various origins, including carcinomas from breast, colon, lung, stomach, esophagus, liver, prostate, urinary bladder, ovary, uterine cervix, skin and kidney, and malignant mesotheliomas, primary GBM, malignant meningiomas, multiple myelomas and acute leukemias by single-strand conformation polymorphism analysis. We found four IDH1 codon 132 mutations in the GBM (4/25; 16.0%), two in the prostate carcinomas (2/75; 2.7%) and one in the B-acute lymphoblastic leukemias (B-ALL) (1/60; 1.7%), but none in other cancers. The IDH1 mutations consisted of five p.R132H and two p.R132C mutations. The data indicate that IDH1 codon 132 mutations occur not only in GBM, but also in prostate cancers and B-ALL. This study suggests that despite the infrequent incidence of the IDH1 mutations in prostate cancers and B-ALL, mutated IDH1 could be therapeutically targeted in these cancers and in glial tumors with the IDH1 mutations. PMID:19378339

  9. HER2 codon 655 polymorphism and breast cancer risk: a meta-analysis.

    PubMed

    Tao, Weiyang; Wang, Chunyang; Han, Ruifa; Jiang, Hongchi

    2009-03-01

    To evaluate the association between HER2 codon 655 polymorphism and breast cancer risk in this meta-analysis. A comprehensive search was performed to identify all case-control studies investigating such association. Statistical analyses were conducted with software MIX 1.54. Twenty eligible reports, including 10,642 cases/11,259 controls, were identified. In overall analysis, the Val allele frequency in cases was significantly higher than that in controls (OR = 1.0921, 95% CI: 1.0013-1.191, P = 0.0466), while no associations were found in both recessive and dominant models. In subgroup analysis, HER2 codon 655 polymorphism was weakly associated with breast cancer risk in recessive (OR = 2.4624, 95% CI: 1.0619-5.7104, P = 0.0357), dominant (OR = 1.2781, 95% CI: 1.0353-1.5779, P = 0.0225), and co-dominant genetic models (OR = 1.2947, 95% CI: 1.0682-1.5693, P = 0.0085) in Asian population, respectively. Meanwhile, the susceptibility to breast cancer in people aged < or =45 was significantly increased in both recessive (OR = 2.2408; 95% CI: 1.2876-3.8998, P = 0.0043), and dominant models (OR = 1.2902, 95% CI: 1.1035-1.5085, P = 0.0014). No significant associations were observed in Caucasian, European, and Family history subgroups. So our analyses suggest HER2 codon 655 Val allele is weakly associated with an increased risk of breast cancer, and SNP at HER2 codon 655 could be considered as a susceptibility biomarker for breast cancer for Asian females or women age 45 years or younger. PMID:18438707

  10. Mechanism of codon recognition by transfer RNA studied with oligonucleotides larger than triplets.

    PubMed Central

    Labuda, D; Striker, G; Grosjean, H; Porschke, D

    1985-01-01

    The binding of yeast tRNAPhe to UUCA, UUCC, UUCCC, UUCUUCU, U4, U5, U6 and U7 was analysed by fluorescence temperature jump and equilibrium sedimentation measurements. In all cases the two observed relaxation processes can be assigned to alpha) an intramolecular conformation change of the anticodon loop and beta) preferential binding of the oligonucleotides to one of the anticodon conformations. The anticodon loop transition is associated with inner sphere complexation of Mg2+ and proceeds with rate constants of about 10(3) s-1. The rate constants of oligonucleotide binding are between 4 and 10 X 10(6) M-1s-1 and reflect an increase of the association rate with the number of binding sites compensated to some degree by electrostatic repulsion in the preequilibrium complex. Neither temperature jump nor equilibrium sedimentation experiments provided evidence for UUCA or UUCC induced tRNA dimerisation, although UUC binding leads to strong tRNA dimerisation under equivalent conditions. The results obtained for the longer oligonucleotides are similar. In the case of UUCUUCU with its two potential binding sites for tRNAPhe there was no evidence for the formation of 'ternary' complexes. Apparently tRNAPhe binds preferentially to the second UUC of this 'messenger' and forms additional contacts with residues on either side of the codon. Some evidence for the formation of ternary complexes is obtained for U6 and U7, although the extent of this reaction remains very small. Our results demonstrate that the mode of tRNA binding to a codon is strongly influenced by residues next to the codon. The formation of cooperative contacts between tRNA molecules at adjacent codons apparently requires support by a catalyst adjusting an appropriate conformation of messenger and tRNA molecules. PMID:4011439

  11. Mitochondrial phylogenomics of early land plants: mitigating the effects of saturation, compositional heterogeneity, and codon-usage bias.

    PubMed

    Liu, Yang; Cox, Cymon J; Wang, Wei; Goffinet, Bernard

    2014-11-01

    Phylogenetic analyses using concatenation of genomic-scale data have been seen as the panacea for resolving the incongruences among inferences from few or single genes. However, phylogenomics may also suffer from systematic errors, due to the, perhaps cumulative, effects of saturation, among-taxa compositional (GC content) heterogeneity, or codon-usage bias plaguing the individual nucleotide loci that are concatenated. Here, we provide an example of how these factors affect the inferences of the phylogeny of early land plants based on mitochondrial genomic data. Mitochondrial sequences evolve slowly in plants and hence are thought to be suitable for resolving deep relationships. We newly assembled mitochondrial genomes from 20 bryophytes, complemented these with 40 other streptophytes (land plants plus algal outgroups), compiling a data matrix of 60 taxa and 41 mitochondrial genes. Homogeneous analyses of the concatenated nucleotide data resolve mosses as sister-group to the remaining land plants. However, the corresponding translated amino acid data support the liverwort lineage in this position. Both results receive weak to moderate support in maximum-likelihood analyses, but strong support in Bayesian inferences. Tests of alternative hypotheses using either nucleotide or amino acid data provide implicit support for their respective optimal topologies, and clearly reject the hypotheses that bryophytes are monophyletic, liverworts and mosses share a unique common ancestor, or hornworts are sister to the remaining land plants. We determined that land plant lineages differ in their nucleotide composition, and in their usage of synonymous codon variants. Composition heterogeneous Bayesian analyses employing a nonstationary model that accounts for variation in among-lineage composition, and inferences from degenerated nucleotide data that avoid the effects of synonymous substitutions that underlie codon-usage bias, again recovered liverworts being sister to the

  12. Mismatch repair at stop codons is directed independent of GATC methylation on the Escherichia coli chromosome

    NASA Astrophysics Data System (ADS)

    Sneppen, Kim; Semsey, Szabolcs

    2014-12-01

    The mismatch repair system (MMR) corrects replication errors that escape proofreading. Previous studies on extrachromosomal DNA in Escherichia coli suggested that MMR uses hemimethylated GATC sites to identify the newly synthesized strand. In this work we asked how the distance of GATC sites and their methylation status affect the occurrence of single base substitutions on the E. coli chromosome. As a reporter system we used a lacZ gene containing an early TAA stop codon. We found that occurrence of point mutations at this stop codon is unaffected by GATC sites located more than 115 base pairs away. However, a GATC site located about 50 base pairs away resulted in a decreased mutation rate. This effect was independent of Dam methylation. The reversion rate of the stop codon increased only slightly in dam mutants compared to mutL and mutS mutants. We suggest that unlike on extrachromosomal DNA, GATC methylation is not the only strand discrimination signal for MMR on the E. coli chromosome.

  13. Mismatch repair at stop codons is directed independent of GATC methylation on the Escherichia coli chromosome.

    PubMed

    Sneppen, Kim; Semsey, Szabolcs

    2014-01-01

    The mismatch repair system (MMR) corrects replication errors that escape proofreading. Previous studies on extrachromosomal DNA in Escherichia coli suggested that MMR uses hemimethylated GATC sites to identify the newly synthesized strand. In this work we asked how the distance of GATC sites and their methylation status affect the occurrence of single base substitutions on the E. coli chromosome. As a reporter system we used a lacZ gene containing an early TAA stop codon. We found that occurrence of point mutations at this stop codon is unaffected by GATC sites located more than 115 base pairs away. However, a GATC site located about 50 base pairs away resulted in a decreased mutation rate. This effect was independent of Dam methylation. The reversion rate of the stop codon increased only slightly in dam mutants compared to mutL and mutS mutants. We suggest that unlike on extrachromosomal DNA, GATC methylation is not the only strand discrimination signal for MMR on the E. coli chromosome. PMID:25475788

  14. Comparison of two codon optimization strategies enhancing recombinant Sus scrofa lysozyme production in Pichia pastoris.

    PubMed

    Zhu, D; Cai, G; Wu, D; Lu, J

    2015-01-01

    Lysozyme has played an important role in animal feed additive industry, food additive industry and biological engineering. For improving expression efficiency of recombinant lysozyme from Sus scrofa, two genes respectively designed by the most used codon optimization strategies, "one amino acid one codon" and "codon randomization", were synthesized and expressed in Pichia pastoris X—33. At shaking flask level, Sus scrofa lysozyme (SSL) under two conditions had a highest activity of 153.33±10.41 and 538.33±15.18 U/mL after a 5 days induction of 1% methanol, with secreted protein concentration 80.03±1.94 and 239.60±4.16 mg/L, respectively. Compared with the original SSL gene, the expression of optimized SSL gene by the second strategy showed a 2.6 fold higher level, while the first method had no obvious improvement in production. In total secreted protein, the proportions of recombinant SSL encoded by the original gene, first method optimized gene and the second—strategy optimized one were 75.06±0.25%, 74.56±0.14% and 79.00±0.14%, respectively, with the same molecular weight about 18 kDa, optimum acidity pH 6.0 and optimum temperature 35degC. PMID:26025401

  15. Highly reproductive Escherichia coli cells with no specific assignment to the UAG codon

    PubMed Central

    Mukai, Takahito; Hoshi, Hiroko; Ohtake, Kazumasa; Takahashi, Mihoko; Yamaguchi, Atsushi; Hayashi, Akiko; Yokoyama, Shigeyuki; Sakamoto, Kensaku

    2015-01-01

    Escherichia coli is a widely used host organism for recombinant technology, and the bacterial incorporation of non-natural amino acids promises the efficient synthesis of proteins with novel structures and properties. In the present study, we developed E. coli strains in which the UAG codon was reserved for non-natural amino acids, without compromising the reproductive strength of the host cells. Ninety-five of the 273 UAG stop codons were replaced synonymously in the genome of E. coli BL21(DE3), by exploiting the oligonucleotide-mediated base-mismatch-repair mechanism. This genomic modification allowed the safe elimination of the UAG-recognizing cellular component (RF-1), thus leaving the remaining 178 UAG codons with no specific molecule recognizing them. The resulting strain B-95.ΔA grew as vigorously as BL21(DE3) in rich medium at 25–42°C, and its derivative B-95.ΔAΔfabR was better adapted to low temperatures and minimal media than B-95.ΔA. UAG was reassigned to synthetic amino acids by expressing the specific pairs of UAG-reading tRNA and aminoacyl-tRNA synthetase. Due to the preserved growth vigor, the B-95.ΔA strains showed superior productivities for hirudin molecules sulfonated on a particular tyrosine residue, and the Fab fragments of Herceptin containing multiple azido groups. PMID:25982672

  16. Optimization of Codon Translation Rates via tRNA Modifications Maintains Proteome Integrity

    PubMed Central

    Nedialkova, Danny D.; Leidel, Sebastian A.

    2015-01-01

    Summary Proteins begin to fold as they emerge from translating ribosomes. The kinetics of ribosome transit along a given mRNA can influence nascent chain folding, but the extent to which individual codon translation rates impact proteome integrity remains unknown. Here, we show that slower decoding of discrete codons elicits widespread protein aggregation in vivo. Using ribosome profiling, we find that loss of anticodon wobble uridine (U34) modifications in a subset of tRNAs leads to ribosome pausing at their cognate codons in S. cerevisiae and C. elegans. Cells lacking U34 modifications exhibit gene expression hallmarks of proteotoxic stress, accumulate aggregates of endogenous proteins, and are severely compromised in clearing stress-induced protein aggregates. Overexpression of hypomodified tRNAs alleviates ribosome pausing, concomitantly restoring protein homeostasis. Our findings demonstrate that modified U34 is an evolutionarily conserved accelerator of decoding and reveal an unanticipated role for tRNA modifications in maintaining proteome integrity. PMID:26052047

  17. Structural Changes Enable Start Codon Recognition by the Eukaryotic Translation Initiation Complex

    PubMed Central

    Hussain, Tanweer; Llácer, Jose L.; Fernández, Israel S.; Munoz, Antonio; Martin-Marcos, Pilar; Savva, Christos G.; Lorsch, Jon R.; Hinnebusch, Alan G.; Ramakrishnan, V.

    2014-01-01

    Summary During eukaryotic translation initiation, initiator tRNA does not insert fully into the P decoding site on the 40S ribosomal subunit. This conformation (POUT) is compatible with scanning mRNA for the AUG start codon. Base pairing with AUG is thought to promote isomerization to a more stable conformation (PIN) that arrests scanning and promotes dissociation of eIF1 from the 40S subunit. Here, we present a cryoEM reconstruction of a yeast preinitiation complex at 4.0 Å resolution with initiator tRNA in the PIN state, prior to eIF1 release. The structure reveals stabilization of the codon-anticodon duplex by the N-terminal tail of eIF1A, changes in the structure of eIF1 likely instrumental in its subsequent release, and changes in the conformation of eIF2. The mRNA traverses the entire mRNA cleft and makes connections to the regulatory domain of eIF2α, eIF1A, and ribosomal elements that allow recognition of context nucleotides surrounding the AUG codon. PMID:25417110

  18. Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation

    PubMed Central

    Deng, Wenjun; Babu, I. Ramesh; Su, Dan; Yin, Shanye; Begley, Thomas J.; Dedon, Peter C.

    2015-01-01

    Post-transcriptional modifications of transfer RNAs (tRNAs) have long been recognized to play crucial roles in regulating the rate and fidelity of translation. However, the extent to which they determine global protein production remains poorly understood. Here we use quantitative proteomics to show a direct link between wobble uridine 5-methoxycarbonylmethyl (mcm5) and 5-methoxy-carbonyl-methyl-2-thio (mcm5s2) modifications catalyzed by tRNA methyltransferase 9 (Trm9) in tRNAArg(UCU) and tRNAGlu(UUC) and selective translation of proteins from genes enriched with their cognate codons. Controlling for bias in protein expression and alternations in mRNA expression, we find that loss of Trm9 selectively impairs expression of proteins from genes enriched with AGA and GAA codons under both normal and stress conditions. Moreover, we show that AGA and GAA codons occur with high frequency in clusters along the transcripts, which may play a role in modulating translation. Consistent with these results, proteins subject to enhanced ribosome pausing in yeast lacking mcm5U and mcm5s2U are more likely to be down-regulated and contain a larger number of AGA/GAA clusters. Together, these results suggest that Trm9-catalyzed tRNA modifications play a significant role in regulating protein expression within the cell. PMID:26670883

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

    PubMed Central

    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. PMID:25237653

  20. Effect of codon optimisation on the production of recombinant fish growth hormone in Pichia pastoris.

    PubMed

    Rothan, Hussin A; Huy, Teh Ser; Mohamed, Zulqarnain

    2014-01-01

    This study was established to test the hypothesis of whether the codon optimization of fish growth hormone gene (FGH) based on P. pastoris preferred codon will improve the quantity of secreted rFGH in culture supernatant that can directly be used as fish feed supplements. The optimized FGH coding sequence (oFGH) and native sequence (nFGH) of giant grouper fish (Epinephelus lanceolatus) were cloned into P. pastoris expression vector (pPICZαA) downstream of alcohol oxidase gene (AOX1) for efficient induction of extracellular rFGH by adding 1% of absolute methanol. The results showed that recombinant P. pastoris was able to produce 2.80 ± 0.27 mg of oFGH compared to 1.75 ± 0.25 of nFGH in one litre of culture supernatant. The total body weight of tiger grouper fingerlings fed with oFGH increased significantly at third (P < 0.05) and fourth weeks (P < 0.01) of four-week experiment period compared to those fed with nFGH. Both oFGH and nFGH significantly enhanced the final biomass and fish survival percentage. In conclusion, codon optimization of FGH fragment was useful to increase rFGH quantity in the culture supernatant of P. pastoris that can be directly used as fish feed supplements. Further studies are still required for large scale production of rFGH and practical application in aquaculture production. PMID:25147851

  1. The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences.

    PubMed Central

    Williams, N P; Mueller, P P; Hinnebusch, A G

    1988-01-01

    Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function. Images PMID:3065626

  2. Downregulating viral gene expression: codon usage bias manipulation for the generation of novel influenza A virus vaccines

    PubMed Central

    Baker, Steven F; Nogales, Aitor; Martínez-Sobrido, Luis

    2015-01-01

    Vaccination represents the best option to protect humans against influenza virus. However, improving the effectiveness of current vaccines could better stifle the health burden caused by viral infection. Protein synthesis from individual genes can be downregulated by synthetically deoptimizing a gene’s codon usage. With more rapid and affordable nucleotide synthesis, generating viruses that contain genes with deoptimized codons is now feasible. Attenuated, vaccine-candidate viruses can thus be engineered with hitherto uncharacterized properties. With eight gene segments, influenza A viruses with variably recoded genomes can produce a spectrum of attenuation that is contingent on the gene segment targeted and the number of codon changes. This review summarizes different targets and approaches to deoptimize influenza A virus codons for novel vaccine generation. PMID:26213563

  3. Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds

    PubMed Central

    Zadeh, Reza Ashrafi; Omrani, Mir Davood; Ramezani, Fatemeh; Amniattalab, Amir

    2011-01-01

    PrP genotypes at codons 136 and 171 in 120 Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated. PMID:21778818

  4. Self-catalytic DNA depurination underlies human β-globin gene mutations at codon 6 that cause anemias and thalassemias.

    PubMed

    Alvarez-Dominguez, Juan R; Amosova, Olga; Fresco, Jacques R

    2013-04-19

    The human β-globin gene contains an 18-nucleotide coding strand sequence centered at codon 6 and capable of forming a stem-loop structure that can self-catalyze depurination of the 5'G residue of that codon. The resultant apurinic lesion is subject to error-prone repair, consistent with the occurrence about this codon of mutations responsible for 6 anemias and β-thalassemias and additional substitutions without clinical consequences. The 4-residue loop of this stem-loop-forming sequence shows the highest incidence of mutation across the gene. The loop and first stem base pair-forming residues appeared early in the mammalian clade. The other stem-forming segments evolved more recently among primates, thereby conferring self-depurination capacity at codon 6. These observations indicate a conserved molecular mechanism leading to β-globin variants underlying phenotypic diversity and disease. PMID:23457306

  5. Differentiating between Near- and Non-Cognate Codons in Saccharomyces cerevisiae

    PubMed Central

    Plant, Ewan P.; Nguyen, Phuc; Russ, Jonathan R.; Pittman, Yvette R.; Nguyen, Thai; Quesinberry, Jack T.; Kinzy, Terri Goss; Dinman, Jonathan D.

    2007-01-01

    Background Decoding of mRNAs is performed by aminoacyl tRNAs (aa-tRNAs). This process is highly accurate, however, at low frequencies (10−3 – 10−4) the wrong aa-tRNA can be selected, leading to incorporation of aberrant amino acids. Although our understanding of what constitutes the correct or cognate aa-tRNA:mRNA interaction is well defined, a functional distinction between near-cognate or single mismatched, and unpaired or non-cognate interactions is lacking. Methodology/Principal Findings Misreading of several synonymous codon substitutions at the catalytic site of firefly luciferase was assayed in Saccharomyces cerevisiae. Analysis of the results in the context of current kinetic and biophysical models of aa-tRNA selection suggests that the defining feature of near-cognate aa-tRNAs is their potential to form mini-helical structures with A-site codons, enabling stimulation of GTPase activity of eukaryotic Elongation Factor 1A (eEF1A). Paromomycin specifically stimulated misreading of near-cognate but not of non-cognate aa-tRNAs, providing a functional probe to distinguish between these two classes. Deletion of the accessory elongation factor eEF1Bγ promoted increased misreading of near-cognate, but hyperaccurate reading of non-cognate codons, suggesting that this factor also has a role in tRNA discrimination. A mutant of eEF1Bα, the nucleotide exchange factor for eEF1A, promoted a general increase in fidelity, suggesting that the decreased rates of elongation may provide more time for discrimination between aa-tRNAs. A mutant form of ribosomal protein L5 promoted hyperaccurate decoding of both types of codons, even though it is topologically distant from the decoding center. Conclusions/Signficance It is important to distinguish between near-cognate and non-cognate mRNA:tRNA interactions, because such a definition may be important for informing therapeutic strategies for suppressing these two different categories of mutations underlying many human

  6. A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B, non-C chronic hepatitis.

    PubMed

    Fujise, Kiyotaka; Tatsuzawa, Keiko; Kono, Midori; Hoshina, Sadayori; Tsubota, Akihito; Niiya, Minoru; Namiki, Yoshihisa; Tada, Norio; Tajiri, Hisao

    2011-02-27

    There are cases of hepatitis involving occult hepatitis B virus (HBV) infection in which, even though the HB surface antigen (HBsAg) is negative, HBV-DNA is detected by a polymerase chain reaction (PCR). We conducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-year-old female. A diagnosis of non-B non-C chronic hepatitis was made. Although HBV markers, such as HBs antibody (anti-HBs), anti-HBc, HBeAg and anti-HBe, were negative, HBV-DNA was positive. Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR. Sequence analysis of the two obtained bands was conducted by direct sequencing. Compared with the control strains, the ATG (Methionine) start codon in the X region had mutated to GTG (Valine). It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection. PMID:21423595

  7. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

    PubMed

    Kirchhof, Paulus; Lip, Gregory Y H; Van Gelder, Isabelle C; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  8. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

    PubMed Central

    Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  9. Genome-wide survey of codons under diversifying selection in a highly recombining bacterial species, Helicobacter pylori

    PubMed Central

    Yahara, Koji; Furuta, Yoshikazu; Morimoto, Shinpei; Kikutake, Chie; Komukai, Sho; Matelska, Dorota; Dunin-Horkawicz, Stanisław; Bujnicki, Janusz M.; Uchiyama, Ikuo; Kobayashi, Ichizo

    2016-01-01

    Selection has been a central issue in biology in eukaryotes as well as prokaryotes. Inference of selection in recombining bacterial species, compared with clonal ones, has been a challenge. It is not known how codons under diversifying selection are distributed along the chromosome or among functional categories or how frequently such codons are subject to mutual homologous recombination. Here, we explored these questions by analysing genes present in >90% among 29 genomes of Helicobacter pylori, one of the bacterial species with the highest mutation and recombination rates. By a method for recombining sequences, we identified codons under diversifying selection (dN/dS > 1), which were widely distributed and accounted for ∼0.2% of all the codons of the genome. The codons were enriched in genes of host interaction/cell surface and genome maintenance (DNA replication, recombination, repair, and restriction modification system). The encoded amino acid residues were sometimes found adjacent to critical catalytic/binding residues in protein structures. Furthermore, by estimating the intensity of homologous recombination at a single nucleotide level, we found that these codons appear to be more frequently subject to recombination. We expect that the present study provides a new approach to population genomics of selection in recombining prokaryotes. PMID:26961370

  10. Deviation from major codons in the Toll-like receptor genes is associated with low Toll-like receptor expression

    PubMed Central

    Zhong, Fei; Cao, Weiping; Chan, Edmund; Tay, Puei Nam; Cahya, Florence Feby; Zhang, Haifeng; Lu, Jinhua

    2005-01-01

    Microbial structures activate Toll-like receptors (TLRs) and TLR-mediated cell signalling elicits and regulates host immunity. Most TLRs are poorly expressed but the underlying expression mechanism is not clear. Examination TLR sequences revealed that most human TLR genes deviated from using major human codons. CD14 resembles TLRs in sequence but its gene preferentially uses major codons. Indeed, CD14 expression on monocytes was higher than expression of TLR1 and TLR2. The TLR9 gene is abundant in major codons and it also showed higher expression than TLR1, TLR2 and TLR7 in transfected 293T cells. Change of the 5′-end 302 base pairs of the TLR2 sequence into major human codons markedly increased TLR2 expression, which led to increased TLR2-mediated constitutive nuclear factor-κB activation. Change of the 5′-end 381 base pairs of the CD14 sequence into prevalent TLR codons markedly reduced CD14 expression. These results collectively show that the deviation of TLR sequences from using major codons dictates the low TLR expression and this may protect the host against excessive inflammation and tissue damages. PMID:15606798

  11. The Association Between p53 Codon 72 Polymorphism and Endometrial Cancer Risk: A System Review and Meta-analysis.

    PubMed

    Yi, Ke; Yang, LingYun; Lan, Zhu; Xi, MingRong

    2016-07-01

    Polymorphism of p53 codon 72 plays an important role in pathogenesis and development of cancer. Published data on the association between the p53 codon 72 polymorphism and endometrial cancer risk are controversial. A meta-analysis was performed to assess whether the polymorphism of p53 codon 72 is associated with endometrial cancer risk. Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for p53 codon 72 polymorphism and endometrial cancer were appropriately derived from fixed-effects or random effects models. A total of 12 studies were enrolled in this meta-analysis. The pooled analyses revealed that p53 codon 72 polymorphism was not associated with endometrial cancer risk. Stratified analysis by Hardy-Weinberg equilibrium exhibited a significantly increased risk of endometrial cancer among studies deviated from Hardy-Weinberg equilibrium in heterozygote comparison (Pro/Arg vs Arg/Arg; OR, 0.61; 95% CI, 0.42-0.87) and dominant model (Pro/Pro + Pro/Arg vs Arg/Arg; OR, 0.66; 95% CI, 0.47-0.92). This study indicated that the p53 codon 72 polymorphism may not be associated with endometrial cancer risk. PMID:27327151

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

    PubMed Central

    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. PMID:25200075

  13. Phylogenetic Patterns of Codon Evolution in the ACTIN-DEPOLYMERIZING FACTOR/COFILIN (ADF/CFL) Gene Family

    PubMed Central

    Roy-Zokan, Eileen M.; Dyer, Kelly A.; Meagher, Richard B.

    2015-01-01

    The actin-depolymerizing factor/cofilin (ADF/CFL) gene family encodes a diverse group of relatively small proteins. Once known strictly as modulators of actin filament dynamics, recent research has demonstrated that these proteins are involved in a variety of cellular processes, from signal transduction to the cytonuclear trafficking of actin. In both plant and animal lineages, expression patterns of paralogs in the ADF/CFL gene family vary among tissue types and developmental stages. In this study we use computational approaches to investigate the evolutionary forces responsible for the diversification of the ADF/CFL gene family. Estimating the rate of non-synonymous to synonymous mutations (dN/dS) across phylogenetic lineages revealed that the majority of ADF/CFL codon positions were under strong purifying selection, with rare episodic events of accelerated protein evolution. In both plants and animals these instances of accelerated evolution were ADF/CFL subclass specific, and all of the sites under selection were located in regions of the protein that could serve in new functional roles. We suggest these sites may have been important in the functional diversification of ADF/CFL proteins. PMID:26717562

  14. Lucky guess or knowledge: a cross-sectional study using the Bland and Altman analysis to compare confidence-based testing of pharmacological knowledge in 3rd and 5th year medical students.

    PubMed

    Kampmeyer, Daniela; Matthes, Jan; Herzig, Stefan

    2015-05-01

    Multiple-choice-questions are common in medical examinations, but guessing biases assessment results. Confidence-based-testing (CBT) integrates indicated confidence levels. It has been suggested that correctness of and confidence in an answer together indicate knowledge levels thus determining the quality of a resulting decision. We used a CBT approach to investigate whether decision quality improves during undergraduate medical education. 3rd- and 5th-year students attended formative multiple-choice exams on pharmacological issues. Students were asked to indicate their confidence in a given answer. Correctness of answers was scored binary (1-correct; 0-wrong) and confidence levels were transformed to an ordinal scale (guess: 0; rather unsure: 0.33; rather sure: 0.66; very sure: 1). 5th-year students gave more correct answers (73 ± 16 vs. 49 ± 13 %, p < 0.05) and were on average more confident regarding the correctness of their answers (0.61 ± 0.18 vs. 0.46 ± 0.13, p < 0.05). Correlation of these parameters was stronger for 5th-year students (r = 0.81 vs. r = 0.52), but agreement of confidence and correctness ('centration') was lower. By combining the Bland-and-Altman approach with categories of decision-quality we found that 5th-year students were more likely to be 'well-informed' (41 vs. 5 %), while more 3rd-students were 'uninformed' (24 vs. 76 %). Despite a good correlation of exam results and confidence in given answers increased knowledge might be accompanied by a more critical view at the own abilities. Combining the statistical Bland-and-Altman analysis with a theoretical approach to decision-quality, more advanced students are expected to apply correct beliefs, while their younger fellows are rather at risk to hesitate or to act amiss. PMID:25103688

  15. Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics

    PubMed Central

    Willenbacher, Ella; Weger, Roman; Rochau, Ursula; Siebert, Uwe; Willenbacher, Wolfgang

    2016-01-01

    Objective Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. Methods We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Results Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011–2014, 21% in patients with a diagnosis made between 2000–2005, and 39% in those with a diagnosis made between 2006–2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide—so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). Conclusion & Perspective With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM. PMID:26937956

  16. Acoustic Evidence for Positional and Complexity Effects on Children's Production of Plural "-s"

    ERIC Educational Resources Information Center

    Theodore, Rachel M.; Demuth, Katherine; Shattuck-Hufnagel, Stefanie

    2011-01-01

    Purpose: Some variability in children's early productions of grammatical morphemes reflects phonological factors. For example, production of 3rd person singular "-s" is increased in utterance-final versus utterance-medial position and in simple versus cluster codas (e.g., "sees" vs. "hits"). Understanding the factors that govern such variability…

  17. Fundamentals of nuclear pharmacy, 3rd Ed

    SciTech Connect

    Saha, G.B. )

    1992-01-01

    This book is a standard text/reference of nuclear pharmacy. New sections in the Third Edition include: instruments used for radiation detection and measurement; disposal of radioactive materials; clinical uses of all new and existing radiopharmaceuticals; 99m Tc and 123I-labeled radiopharmaceuticals, as well as radiolabeled leukocytes, platelets, and antibodies; and up-to-date descriptions of the latest FDA regulations.

  18. Cerebral computed tomography, 3rd Edition

    SciTech Connect

    Weisberg, L.; Nice, C.

    1988-01-01

    This book is an introduction to the utilization of computed tomography in evaluating patients with intracranial and orbital disorders. It features clinical correlations and provides an overview of general principles, performance, and normal anatomy of CT. It covers evaluation of specific neurologic signs and symptoms, including stroke, metastatic disease, increased intracranial pressure, head injury, pediatric conditions, and more.

  19. Towards a hydrogen economy. 3rd ed.

    SciTech Connect

    2006-07-15

    The report is a study of the movement towards using hydrogen as a key energy carrier in the future. It takes a look at the current state of hydrogen and addresses the infrastructure requirements needed to make the hydrogen economy a reality. The report offers a detailed look at the move to a hydrogen economy by: Identifying the current status of hydrogen production and use; Discussing the key business drivers of the move towards hydrogen; Discussing the barriers to implementation that stand in the way of a transition; Providing a critical look at whether the hydrogen economy can succeed; Describing the options that exist for a hydrogen infrastructure; Identifying the key government initiatives making the hydrogen economy a reality; Providing company-by-company profiles of automobile manufacturer efforts to develop and commercialize hydrogen vehicles; and Providing profiles of key hydrogen infrastructure manufacturers.

  20. Teaching Visually Impaired Children. 3rd Edition

    ERIC Educational Resources Information Center

    Bishop, Virginia E.

    2004-01-01

    In this exceptional new third edition, the author has retained much of the practical "how to" approach of the previous editions, but adds depth in two dimensions: learning theory and the educational process. This book is "so comprehensive in scope and complete in detail that it would be the most likely recommended" (from the foreword by Dr.…

  1. A Beginning. Revised 3rd Edition.

    ERIC Educational Resources Information Center

    Healy, Mary K.; Root, Phyllis

    This document contains a selection of materials focusing on man acting to know, preserve, and improve his environment. The booklet is divided into three parts. Part one presents a listing of objectives. They reflect a need for all to become aware of the problems that plague our environment. Furthermore, they indicate that the ecological…

  2. Coal mine ground control. 3rd ed.

    SciTech Connect

    Peng, S.S.

    2008-09-15

    The third edition not only completely revises and updates the original subject areas, but also is broadened to include a number of new topics such as high horizontal stresses, computer modeling, and highwall stability. The subject areas covered in this book define the current field of coal mine ground control, except for the recently emerging topic of mine seals and some conventional subjects such as coal/rock cutting and impoundment dams. It contains 1,134 references from all published sources, and archived since 1876.

  3. Elementary Science Guide -- 3rd Grade.

    ERIC Educational Resources Information Center

    Wieland, Anne; And Others

    Presented is a resource book to be used with instructional kits for elementary school science students, grade 3. The individual units at this grade level are based on curriculum which has been developed by the National Science Foundation in the 1960s and revised to meet student and teacher identified needs in Anchorage, Alaska. Six units are…

  4. The Physics of Glaciers, 3rd Edition

    NASA Astrophysics Data System (ADS)

    Bahr, David

    At one time or another, who among us has not marveled at the beauty of the snow and ice-covered Alps, or admired the tenacity of polar explorers and the adventurous spirits of climbers on the glacier-clad summits of the high Himalaya? The fascination of distant ice covered expanses has enlisted more than a few recruits into the ranks of glaciologists, but many, if not most, of today's students of glaciology are a slightly less romantic and more mathematical lot, attracted by the quantitative world of physics and the applied sciences of polar climatology, ice mechanics, and snow hydrology.Once a relatively quiet branch of geophysics filled with venturesome climbers capable of reaching the objects of their study, glaciology is now a field that is fueled by a rapid influx of talent, technology, and new ideas due to the increasingly acknowledged relationships between global climate, sea level, and ice sheets. While the understanding of glacier processes has seen significant progress, as a result there is also a sense of being overwhelmed by the voluminous and sometimes speculative theories and field observations associated with an expanding discipline.

  5. The 3rd International Microgravity Combustion Workshop

    NASA Technical Reports Server (NTRS)

    Ross, Howard D. (Compiler)

    1995-01-01

    This Conference Publication contains 71 papers presented at the Third International Microgravity Combustion Workshop held in Cleveland, Ohio, from April 11 to 13, 1995. The purpose of the workshop was twofold: to exchange information about the progress and promise of combustion science in microgravity and to provide a forum to discuss which areas in microgravity combustion science need to be expanded profitably and which should be included in upcoming NASA Research Announcements (NRA).

  6. Radiation Therapy Physics, 3rd Edition

    NASA Astrophysics Data System (ADS)

    Hendee, William R.; Ibbott, Geoffrey S.; Hendee, Eric G.

    2004-08-01

    The Third Edition of Radiation Therapy Physics addresses in concise fashion the fundamental diagnostic radiologic physics principles as well as their clinical implications. Along with coverage of the concepts and applications for the radiation treatment of cancer patients, the authors have included reviews of the most up-to-date instrumentation and critical historical links. The text includes coverage of imaging in therapy planning and surveillance, calibration protocols, and precision radiation therapy, as well as discussion of relevant regulation and compliance activities. It contains an updated and expanded section on computer applications in radiation therapy and electron beam therapy, and features enhanced user-friendliness and visual appeal with a new, easy-to-follow format, including sidebars and a larger trim size. With its user-friendly presentation and broad, comprehensive coverage of radiotherapy physics, this Third Edition doubles as a medical text and handy professional reference.

  7. Clear air handbook. 3rd edition

    SciTech Connect

    Brownell, F.W.

    1998-07-01

    The Clean Air Act is the most complex piece of environmental legislation ever enacted, and it is constantly evolving. Regulatory proceedings to implement the act and especially the 1990 amendments are ongoing. Further amendments to the act are being considered by Congress. In addition to developing new rules, EPA also continues to supplement existing rules with guidance documents and policy statements--materials critical to evaluating your company's compliance obligations. This book not only continues to provide a broad overview of all the complex regulatory requirements but also brings you up-to-date on all of the most recent developments. Chapters covered include The Federal-State Partnership; The 1990 Amendments; Air Quality Regulations, State Implementation Plans, and the Non-Attainment Program; Control Technology Regulation; Operating and Pre-Construction Permitting Programs; Acid Deposition Control Program; Hazardous Air Pollutants; Regulation of Mobile Sources of Air Pollution; Stratospheric Ozone Protection; Enforcement and Judicial Review; and Current Regulatory and Legislative Trends.

  8. Library Research Workbook. 3rd Edition, Revised.

    ERIC Educational Resources Information Center

    Hitchings, Donna, Ed.; And Others

    Designed to be used in an English course at the University of Houston, this library skills workbook includes lessons and multiple-choice exercises on the following topics: (1) a floor plan of the main university library; (2) catalog records; (3) catalog access points; (4) using the catalogs; (5) locating books; (6) encyclopedias; (7) dictionaries;…

  9. Peace Corps. 3rd Annual Report.

    ERIC Educational Resources Information Center

    Peace Corps, Washington, DC.

    Projects, operations, and future plans are covered in this annual report for the third year of the Peace Corps. An introduction comments on returning volunteers and presents regional maps with tables for Latin America, Africa, Near East and South Asia, and Far East. Section 1 contains letters and reports from volunteers in Peru, Ivory Coast,…

  10. Functional polypeptides can be synthesized from human mitochondrial transcripts lacking termination codons.

    PubMed Central

    Chrzanowska-Lightowlers, Zofia M A; Temperley, Richard J; Smith, Paul M; Seneca, Sara H; Lightowlers, Robert N

    2004-01-01

    The human mitochondrial genome (mtDNA) is a small, circular DNA duplex found in multi-copy in the mitochondrial matrix. It is almost fully transcribed from both strands to produce large polycistronic RNA units that are processed and matured. The 13 mtDNA-encoded polypeptides are translated from mt-mRNAs that have been matured by polyadenylation of their free 3'-termini. A patient with clinical features consistent with an mtDNA disorder was recently shown to carry a microdeletion, resulting in the loss of the termination codon for MTATP6 and in its juxtaposition with MTCO3. Cell lines from this patient exhibited low steady-state levels of RNA14, the bi-cistronic transcript encoding subunits 6 and 8 of the F(o)F(1)-ATP synthase, complex V, consistent with a decreased stability. Recent reports of 'non-stop' mRNA decay systems in the cytosol have failed to determine the fate of gene products derived from transcripts lacking termination codons, although enhanced decay clearly required the 'non-stop' transcripts to be translated. We wished to determine whether functional translation products could still be expressed from non-stop transcripts in the human mitochondrion. Although a minor defect in complex V assembly was noted in the patient-derived cell lines, the steady-state level of ATPase 6 was similar to controls, consistent with the pattern of de novo mitochondrial protein synthesis. Moreover, no significant difference in ATP synthase activity could be detected. We conclude that, in the absence of a functional termination codon, although mitochondrial transcripts are more rapidly degraded, they are also translated to generate stable polypeptides that are successfully integrated into functional enzyme complexes. PMID:14585098

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

    PubMed Central

    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

  12. The TGA codons are present in the open reading frame of selenoprotein P cDNA

    SciTech Connect

    Hill, K.E.; Lloyd, R.S.; Read, R.; Burk, R.F. )

    1991-03-11

    The TGA codon in DNA has been shown to direct incorporation of selenocysteine into protein. Several proteins from bacteria and animals contain selenocysteine in their primary structures. Each of the cDNA clones of these selenoproteins contains one TGA codon in the open reading frame which corresponds to the selenocysteine in the protein. A cDNA clone for selenoprotein P (SeP), obtained from a {gamma}ZAP rat liver library, was sequenced by the dideoxy termination method. The correct reading frame was determined by comparison of the deduced amino acid sequence with the amino acid sequence of several peptides from SeP. Using SeP labelled with {sup 75}Se in vivo, the selenocysteine content of the peptides was verified by the collection of carboxymethylated {sup 77}Se-selenocysteine as it eluted from the amino acid analyzer and determination of the radioactivity contained in the collected samples. Ten TGA codons are present in the open reading frame of the cDNA. Peptide fragmentation studies and the deduced sequence indicate that selenium-rich regions are located close to the carboxy terminus. Nine of the 10 selenocysteines are located in the terminal 26% of the sequence with four in the terminal 15 amino acids. The deduced sequence codes for a protein of 385 amino acids. Cleavage of the signal peptide gives the mature protein with 366 amino acids and a calculated mol wt of 41,052 Da. Searches of PIR and SWISSPROT protein databases revealed no similarity with glutathione peroxidase or other selenoproteins.

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

    PubMed Central

    Puigbò, Pere; Bravo, Ignacio G; Garcia-Vallvé, Santiago

    2008-01-01

    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 , 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. PMID:18230160

  14. Unique graphical representation of protein sequences based on nucleotide triplet codons

    NASA Astrophysics Data System (ADS)

    Randić, Milan; Zupan, Jure; Balaban, Alexandru T.

    2004-10-01

    We consider a graphical representation of proteins as an alternative to the usual representation of proteins as a sequence listing the natural amino acids. The approach is based on a graphical representation of triplets of DNA in which the interior of a square or the interior of a tetrahedron is used to accommodate 64 sites for the 64 codons. By associating a zigzag curve and various matrices with a protein, just as was the case with graphical representation of DNA, one can construct selected invariants to serve as protein descriptors. The approach is illustrated on the A-chain of human insulin.

  15. Selection of aminoacyl-tRNAs at sense codons: the size of the tRNA variable loop determines whether the immediate 3' nucleotide to the codon has a context effect.

    PubMed Central

    Curran, J F; Poole, E S; Tate, W P; Gross, B L

    1995-01-01

    Codon context can affect translational efficiency by several molecular mechanisms. The base stacking interactions between a codon-anticodon complex and the neighboring nucleotide immediately 3' can facilitate translation by amber suppressors and the tRNA structure is also known to modulate the sensitivity to context. In this study the relative rates of aminoacyl-tRNA selection were measured at four sense codons (UGG, CUC, UUC and UCA), in all four 3' nucleotide contexts, through direct competition with a programmed frameshift at a site derived from the release factor 2 gene. Two