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Sample records for codon bias perspective

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

    African Journals Online (AJOL)

    Abdullah

    2014-01-08

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

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

    Indian Academy of Sciences (India)

    2015-06-10

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

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

    African Journals Online (AJOL)

    sunny t

    2016-02-24

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

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

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    Susanta K Behura

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

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    Gerrit Brandis

    2016-03-01

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

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

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    Maddalena Dilucca

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

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

    Science.gov (United States)

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

    2015-01-22

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

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

    Science.gov (United States)

    Fox, Jesse M; Erill, Ivan

    2010-06-01

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

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

    International Nuclear Information System (INIS)

    Barozai, M.Y.; Din, M.

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

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    Wong Emily HM

    2010-08-01

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

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

    KAUST Repository

    Zhang, Zhang

    2012-03-22

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

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

    Directory of Open Access Journals (Sweden)

    Zhang Zhang

    2012-03-01

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

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

    Science.gov (United States)

    Trotta, Edoardo

    2016-05-17

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

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

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    Sailen Barik

    2017-12-01

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

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

    Science.gov (United States)

    Barik, Sailen

    2017-12-01

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

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

    Science.gov (United States)

    Dilucca, Maddalena; Cimini, Giulio; Giansanti, Andrea

    2018-07-15

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

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    Nicholas J Hudson

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

    Bhatia, Sandeep; Sood, Richa; Selvaraj, Pavulraj

    2016-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-08-23

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

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

    Indian Academy of Sciences (India)

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

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

    Science.gov (United States)

    Karniychuk, Uladzimir U

    2016-09-02

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

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

    Directory of Open Access Journals (Sweden)

    Naveen Kumar

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

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

    Science.gov (United States)

    Carlini, David B; Makowski, Matthew

    2015-12-01

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

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

    Science.gov (United States)

    Behura, Susanta K; Severson, David W

    2013-02-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    OpenAIRE

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sergei Kosakovsky Pond

    2010-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

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

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

    Science.gov (United States)

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

    2010-03-05

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

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

    Directory of Open Access Journals (Sweden)

    Lluís Aragonès

    2010-03-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  19. Canine parvovirus type 2 (CPV-2) and Feline panleukopenia virus (FPV) codon bias analysis reveals a progressive adaptation to the new niche after the host jump.

    Science.gov (United States)

    Franzo, Giovanni; Tucciarone, Claudia Maria; Cecchinato, Mattia; Drigo, Michele

    2017-09-01

    Based on virus dependence from host cell machinery, their codon usage is expected to show a strong relation with the host one. Even if this association has been stated, especially for bacteria viruses, the linkage is considered to be less consistent for more complex organisms and a codon bias adaptation after host jump has never been proven. Canine parvovirus type 2 (CPV-2) was selected as a model because it represents a well characterized case of host jump, originating from Feline panleukopenia virus (FPV). The current study demonstrates that the adaptation to specific tissue and host codon bias affected CPV-2 evolution. Remarkably, FPV and CPV-2 showed a higher closeness toward the codon bias of the tissues they display the higher tropism for. Moreover, after the host jump, a clear and significant trend was evidenced toward a reduction in the distance between CPV-2 and the dog codon bias over time. This evidence was not confirmed for FPV, suggesting that an equilibrium has been reached during the prolonged virus-host co-evolution. Additionally, the presence of an intermediate pattern displayed by some strains infecting wild species suggests that these could have facilitated the host switch also by acting on codon bias. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-12-01

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

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

    OpenAIRE

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

    2017-01-01

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

  2. [Correlation of codon biases and potential secondary structures with mRNA translation efficiency in unicellular organisms].

    Science.gov (United States)

    Vladimirov, N V; Likhoshvaĭ, V A; Matushkin, Iu G

    2007-01-01

    Gene expression is known to correlate with degree of codon bias in many unicellular organisms. However, such correlation is absent in some organisms. Recently we demonstrated that inverted complementary repeats within coding DNA sequence must be considered for proper estimation of translation efficiency, since they may form secondary structures that obstruct ribosome movement. We have developed a program for estimation of potential coding DNA sequence expression in defined unicellular organism using its genome sequence. The program computes elongation efficiency index. Computation is based on estimation of coding DNA sequence elongation efficiency, taking into account three key factors: codon bias, average number of inverted complementary repeats, and free energy of potential stem-loop structures formed by the repeats. The influence of these factors on translation is numerically estimated. An optimal proportion of these factors is computed for each organism individually. Quantitative translational characteristics of 384 unicellular organisms (351 bacteria, 28 archaea, 5 eukaryota) have been computed using their annotated genomes from NCBI GenBank. Five potential evolutionary strategies of translational optimization have been determined among studied organisms. A considerable difference of preferred translational strategies between Bacteria and Archaea has been revealed. Significant correlations between elongation efficiency index and gene expression levels have been shown for two organisms (S. cerevisiae and H. pylori) using available microarray data. The proposed method allows to estimate numerically the coding DNA sequence translation efficiency and to optimize nucleotide composition of heterologous genes in unicellular organisms. http://www.mgs.bionet.nsc.ru/mgs/programs/eei-calculator/.

  3. ANCAC: amino acid, nucleotide, and codon analysis of COGs--a tool for sequence bias analysis in microbial orthologs.

    Science.gov (United States)

    Meiler, Arno; Klinger, Claudia; Kaufmann, Michael

    2012-09-08

    The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC's NUCOCOG dataset as the largest one available for that purpose thus far. Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills.

  4. ANCAC: amino acid, nucleotide, and codon analysis of COGs – a tool for sequence bias analysis in microbial orthologs

    Directory of Open Access Journals (Sweden)

    Meiler Arno

    2012-09-01

    Full Text Available Abstract Background The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Results Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC’s NUCOCOG dataset as the largest one available for that purpose thus far. Conclusions Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills.

  5. ANCAC: amino acid, nucleotide, and codon analysis of COGs – a tool for sequence bias analysis in microbial orthologs

    Science.gov (United States)

    2012-01-01

    Background The COG database is the most popular collection of orthologous proteins from many different completely sequenced microbial genomes. Per definition, a cluster of orthologous groups (COG) within this database exclusively contains proteins that most likely achieve the same cellular function. Recently, the COG database was extended by assigning to every protein both the corresponding amino acid and its encoding nucleotide sequence resulting in the NUCOCOG database. This extended version of the COG database is a valuable resource connecting sequence features with the functionality of the respective proteins. Results Here we present ANCAC, a web tool and MySQL database for the analysis of amino acid, nucleotide, and codon frequencies in COGs on the basis of freely definable phylogenetic patterns. We demonstrate the usefulness of ANCAC by analyzing amino acid frequencies, codon usage, and GC-content in a species- or function-specific context. With respect to amino acids we, at least in part, confirm the cognate bias hypothesis by using ANCAC’s NUCOCOG dataset as the largest one available for that purpose thus far. Conclusions Using the NUCOCOG datasets, ANCAC connects taxonomic, amino acid, and nucleotide sequence information with the functional classification via COGs and provides a GUI for flexible mining for sequence-bias. Thereby, to our knowledge, it is the only tool for the analysis of sequence composition in the light of physiological roles and phylogenetic context without requirement of substantial programming-skills. PMID:22958836

  6. Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions.

    Science.gov (United States)

    Subramanian, Abhishek; Sarkar, Ram Rup

    2015-10-01

    Understanding the variations in gene organization and its effect on the phenotype across different Leishmania species, and to study differential clinical manifestations of parasite within the host, we performed large scale analysis of codon usage patterns between Leishmania and other known Trypanosomatid species. We present the causes and consequences of codon usage bias in Leishmania genomes with respect to mutational pressure, translational selection and amino acid composition bias. We establish GC bias at wobble position that governs codon usage bias across Leishmania species, rather than amino acid composition bias. We found that, within Leishmania, homogenous codon context coding for less frequent amino acid pairs and codons avoiding formation of folding structures in mRNA are essentially chosen. We predicted putative differences in global expression between genes belonging to specific pathways across Leishmania. This explains the role of evolution in shaping the otherwise conserved genome to demonstrate species-specific function-level differences for efficient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Mondal, Sunil Kanti; Kundu, Sudip; Das, Rabindranath; Roy, Sujit

    2016-08-01

    Bacteria and archaea have evolved with the ability to fix atmospheric dinitrogen in the form of ammonia, catalyzed by the nitrogenase enzyme complex which comprises three structural genes nifK, nifD and nifH. The nifK and nifD encodes for the beta and alpha subunits, respectively, of component 1, while nifH encodes for component 2 of nitrogenase. Phylogeny based on nifDHK have indicated that Cyanobacteria is closer to Proteobacteria alpha and gamma but not supported by the tree based on 16SrRNA. The evolutionary ancestor for the different trees was also different. The GC1 and GC2% analysis showed more consistency than GC3% which appeared to below for Firmicutes, Cyanobacteria and Euarchaeota while highest in Proteobacteria beta and clearly showed the proportional effect on the codon usage with a few exceptions. Few genes from Firmicutes, Euryarchaeota, Proteobacteria alpha and delta were found under mutational pressure. These nif genes with low and high GC3% from different classes of organisms showed similar expected number of codons. Distribution of the genes and codons, based on codon usage demonstrated opposite pattern for different orientation of mirror plane when compared with each other. Overall our results provide a comprehensive analysis on the evolutionary relationship of the three structural nif genes, nifK, nifD and nifH, respectively, in the context of codon usage bias, GC content relationship and amino acid composition of the encoded proteins and exploration of crucial statistical method for the analysis of positive data with non-constant variance to identify the shape factors of codon adaptation index.

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

    Indian Academy of Sciences (India)

    Prosenjit Paul

    2018-02-20

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

  9. Understanding antigay bias from a cognitive-affective-behavioral perspective.

    Science.gov (United States)

    Callender, Kevin A

    2015-01-01

    In general, United States citizens have become increasingly more accepting of lesbians and gay men over the past few decades. Despite this shift in public attitudes, antigay bias remains openly tolerated, accepted, practiced, and even defended by a substantial portion of the population. This article reviews why and how antigay bias persists using a cognitive-affective-behavioral perspective that touches on sociocognitive factors such as prejudice and stereotyping, as well as features unique to antigay bias, such as its concealable nature. The article concludes with a discussion of how understanding modern antigay bias through a cognitive-affective-behavioral lens can be applied to reduce discrimination against gays and lesbians.

  10. Investigating the effect of externalizing perspectives on cognitives biases

    DEFF Research Database (Denmark)

    Madsen, Fredrik Huitfeldt; Hicks, David L., David

    2007-01-01

    of intelligence analysis. We propose that complexity of maintaining multiple different perspectives the same data is one of the reasons for this. We further propose that a tool that facillitates the externalization multiple perspectives would reduce these biases and hence increase the overall quality...... the number of attacks that “get through”. There are many subproblems of this main problem, one of which is that relative quality of the intelligence analysis is too low [39, We observe that the analysts suffer from cognitive biases, and we assume that this is one of the reasons behind “low” quality...... of intelligence analyses....

  11. Selection of functional 2A sequences within foot-and-mouth disease virus; requirements for the NPGP motif with a distinct codon bias.

    Science.gov (United States)

    Kjær, Jonas; Belsham, Graham J

    2018-01-01

    Foot-and-mouth disease virus (FMDV) has a positive-sense ssRNA genome including a single, large, open reading frame. Splitting of the encoded polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues long), which induces a nonproteolytic, cotranslational "cleavage" at its own C terminus. A conserved feature among variants of 2A is the C-terminal motif N 16 P 17 G 18 /P 19 , where P 19 is the first residue of 2B. It has been shown previously that certain amino acid substitutions can be tolerated at residues E 14 , S 15 , and N 16 within the 2A sequence of infectious FMDVs, but no variants at residues P 17 , G 18 , or P 19 have been identified. In this study, using highly degenerate primers, we analyzed if any other residues can be present at each position of the NPG/P motif within infectious FMDV. No alternative forms of this motif were found to be encoded by rescued FMDVs after two, three, or four passages. However, surprisingly, a clear codon preference for the wt nucleotide sequence encoding the NPGP motif within these viruses was observed. Indeed, the codons selected to code for P 17 and P 19 within this motif were distinct; thus the synonymous codons are not equivalent. © 2018 Kjær and Belsham; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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

    Directory of Open Access Journals (Sweden)

    Tenson Tanel

    2008-10-01

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

  13. Complete mitochondrial genome sequences of three bats species and whole genome mitochondrial analyses reveal patterns of codon bias and lend support to a basal split in Chiroptera.

    Science.gov (United States)

    Meganathan, P R; Pagan, Heidi J T; McCulloch, Eve S; Stevens, Richard D; Ray, David A

    2012-01-15

    Order Chiroptera is a unique group of mammals whose members have attained self-powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Science.gov (United States)

    Singh, Niraj K; Tyagi, Anuj

    2017-07-01

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

  16. Synonymous Codon Usage Analysis of Thirty Two Mycobacteriophage Genomes

    Directory of Open Access Journals (Sweden)

    Sameer Hassan

    2009-01-01

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

  17. Benefits of being biased!

    Indian Academy of Sciences (India)

    Administrator

    Journal of Genetics, Vol. 83, No. 2, August 2004. Keywords. codon bias; alcohol dehydrogenase; Darwinian ... RESEARCH COMMENTARY. Benefits of being biased! SUTIRTH DEY*. Evolutionary Biology Laboratory, Evolutionary & Organismal Biology Unit,. Jawaharlal Nehru Centre for Advanced Scientific Research,.

  18. A Developmental Neuroscience Perspective on Affect-Biased Attention

    Science.gov (United States)

    Morales, Santiago; Fu, Xiaoxue; Pérez-Edgar, Koraly E.

    2016-01-01

    There is growing interest regarding the impact of affect-biased attention on psychopathology. However, most of the research to date lacks a developmental approach. In the present review, we examine the role affect-biased attention plays in shaping socioemotional trajectories within a developmental neuroscience framework. We propose that affect-biased attention, particularly if stable and entrenched, acts as a developmental tether that helps sustain early socioemotional and behavioral profiles over time, placing some individuals on maladaptive developmental trajectories. Although most of the evidence is found in the anxiety literature, we suggest that these relations may operate across multiple domains of interest, including positive affect, externalizing behaviors, drug use, and eating behaviors. We also review the general mechanisms and neural correlates of affect-biased attention, as well as the current evidence for the co-development of attention and affect. Based on the reviewed literature, we propose a model that may help us better understand the nuances of affect-biased attention across development. The model may serve as a strong foundation for ongoing attempts to identify neurocognitive mechanisms and intervene with individuals at risk. Finally, we discuss open issues for future research that may help bridge existing gaps in the literature. PMID:27606972

  19. "Fair Play": A Videogame Designed to Address Implicit Race Bias Through Active Perspective Taking.

    Science.gov (United States)

    Gutierrez, Belinda; Kaatz, Anna; Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem; Carnes, Molly

    2014-12-01

    Having diverse faculty in academic health centers will help diversify the healthcare workforce and reduce health disparities. Implicit race bias is one factor that contributes to the underrepresentation of Black faculty. We designed the videogame "Fair Play" in which players assume the role of a Black graduate student named Jamal Davis. As Jamal, players experience subtle race bias while completing "quests" to obtain a science degree. We hypothesized that participants randomly assigned to play the game would have greater empathy for Jamal and lower implicit race bias than participants randomized to read narrative text describing Jamal's experience. University of Wisconsin-Madison graduate students were recruited via e-mail and randomly assigned to play "Fair Play" or read narrative text through an online link. Upon completion, participants took an Implicit Association Test to measure implicit bias and answered survey questions assessing empathy toward Jamal and awareness of bias. As hypothesized, gameplayers showed the least implicit bias but only when they also showed high empathy for Jamal (P=0.013). Gameplayers did not show greater empathy than text readers, and women in the text condition reported the greatest empathy for Jamal (P=0.008). However, high empathy only predicted lower levels of implicit bias among those who actively took Jamal's perspective through gameplay (P=0.014). A videogame in which players experience subtle race bias as a Black graduate student has the potential to reduce implicit bias, possibly because of a game's ability to foster empathy through active perspective taking.

  20. Attentional bias for emotional information in older adults: the role of emotion and future time perspective.

    Science.gov (United States)

    Demeyer, Ineke; De Raedt, Rudi

    2013-01-01

    Research suggests that older adults display a positivity bias at the level of information processing. However, because studies investigating attentional bias for emotional information in older adults have produced mixed findings, research identifying inter-individual differences that may explain these inconsistent results is necessary. Therefore, we investigated whether mood, symptoms of depression, symptoms of anxiety and future time perspective are related to attentional bias in older adults. Thirty-seven healthy older adults and 25 healthy middle-aged adults completed questionnaires to assess mood, symptoms of depression, symptoms of anxiety and future time perspective. Attentional bias towards happy, sad and neutral information was measured using a modified exogenous cueing paradigm with long cue presentations, to measure maintained attention versus avoidance of emotional stimuli. Older adults showed attentional avoidance for all emotional faces, whereas no attentional biases were found in the middle-aged group. Moreover, in the older adult group, avoidance for negative information was related to anxiety. Future time perspective was unrelated to attentional bias. These findings suggest that anxiety may lead to inter-individual differences in attentional bias in older adults, and that avoidance from negative information may be an emotion regulation strategy.

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

    Science.gov (United States)

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

    2002-07-01

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

  2. Complex Codon Usage Pattern and Compositional Features of Retroviruses

    Directory of Open Access Journals (Sweden)

    Sourav RoyChoudhury

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

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

  4. Gender bias in leader evaluations: merging implicit theories and role congruity perspectives.

    Science.gov (United States)

    Hoyt, Crystal L; Burnette, Jeni L

    2013-10-01

    This research extends our understanding of gender bias in leader evaluations by merging role congruity and implicit theory perspectives. We tested and found support for the prediction that the link between people's attitudes regarding women in authority and their subsequent gender-biased leader evaluations is significantly stronger for entity theorists (those who believe attributes are fixed) relative to incremental theorists (those who believe attributes are malleable). In Study 1, 147 participants evaluated male and female gubernatorial candidates. Results supported predictions, demonstrating that traditional attitudes toward women in authority significantly predicted a pro-male gender bias in leader evaluations (and progressive attitudes predicted a pro-female gender bias) with an especially strong effect for those with more entity-oriented, relative to incrementally oriented person theories. Study 2 (119 participants) replicated these findings and demonstrated the mediating role of these attitudes in linking gender stereotypes and leader role expectations to biased evaluations.

  5. Endogenous Oxytocin Release Eliminates In-Group Bias in Monetary Transfers With Perspective-Taking

    Directory of Open Access Journals (Sweden)

    Elizabeth T. Terris

    2018-03-01

    Full Text Available Oxytocin (OT has been shown to facilitate trust, empathy and other prosocial behaviors. At the same time, there is evidence that exogenous OT infusion may not result in prosocial behaviors in all contexts, increasing in-group biases in a number of studies. The current investigation seeks to resolve this inconsistency by examining if endogenous OT release is associated with in-group bias. We studied a large group of participants (N = 399 in existing groups and randomly formed groups. Participants provided two blood samples to measure the change in OT after a group salience task and then made computer-mediated monetary transfer decisions to in-group and out-group members. Our results show that participants with an increase in endogenous OT showed no bias in monetary offers in the ultimatum game (UG to out-group members compared to in-groups. There was also no bias in accepting UG offers, though in-group bias persisted for a unilateral monetary transfer. Our analysis shows that the strength of identification with one’s group diminished the effects that an increase in OT had on reducing bias, but bias only recurred when group identification reached 87% of its maximum value. Our results indicate that the endogenous OT system appears to reduce in-group bias in some contexts, particularly those that require perspective-taking.

  6. Endogenous Oxytocin Release Eliminates In-Group Bias in Monetary Transfers With Perspective-Taking.

    Science.gov (United States)

    Terris, Elizabeth T; Beavin, Laura E; Barraza, Jorge A; Schloss, Jeff; Zak, Paul J

    2018-01-01

    Oxytocin (OT) has been shown to facilitate trust, empathy and other prosocial behaviors. At the same time, there is evidence that exogenous OT infusion may not result in prosocial behaviors in all contexts, increasing in-group biases in a number of studies. The current investigation seeks to resolve this inconsistency by examining if endogenous OT release is associated with in-group bias. We studied a large group of participants ( N = 399) in existing groups and randomly formed groups. Participants provided two blood samples to measure the change in OT after a group salience task and then made computer-mediated monetary transfer decisions to in-group and out-group members. Our results show that participants with an increase in endogenous OT showed no bias in monetary offers in the ultimatum game (UG) to out-group members compared to in-groups. There was also no bias in accepting UG offers, though in-group bias persisted for a unilateral monetary transfer. Our analysis shows that the strength of identification with one's group diminished the effects that an increase in OT had on reducing bias, but bias only recurred when group identification reached 87% of its maximum value. Our results indicate that the endogenous OT system appears to reduce in-group bias in some contexts, particularly those that require perspective-taking.

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

    Science.gov (United States)

    Morton, B R

    1993-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Oliveira José L

    2007-11-01

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

  9. Genomic composition factors affect codon usage in porcine genome

    African Journals Online (AJOL)

    j.khobondo

    2015-01-28

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

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

    Directory of Open Access Journals (Sweden)

    Pramod Shinde

    2017-10-01

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

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

    Science.gov (United States)

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

    2016-02-24

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

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

    Science.gov (United States)

    Bae, Young-An

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhu-Qing Shao

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

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

    Science.gov (United States)

    Sun, Yu; Tamarit, Daniel

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2017-04-20

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

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

    Science.gov (United States)

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

    2015-08-26

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

  18. Thinking from God's perspective decreases biased valuation of the life of a nonbeliever.

    Science.gov (United States)

    Ginges, Jeremy; Sheikh, Hammad; Atran, Scott; Argo, Nichole

    2016-01-12

    Religious belief is often thought to motivate violence because it is said to promote norms that encourage tribalism and the devaluing of the lives of nonbelievers. If true, this should be visible in the multigenerational violent conflict between Palestinians and Israelis which is marked by a religious divide. We conducted experiments with a representative sample of Muslim Palestinian youth (n = 555), examining whether thinking from the perspective of Allah (God), who is the ultimate arbitrator of religious belief, changes the relative value of Jewish Israelis' lives (compared with Palestinian lives). Participants were presented with variants of the classic "trolley dilemma," in the form of stories where a man can be killed to save the lives of five children who were either Jewish Israeli or Palestinian. They responded from their own perspective and from the perspective of Allah. We find that whereas a large proportion of participants were more likely to endorse saving Palestinian children than saving Jewish Israeli children, this proportion decreased when thinking from the perspective of Allah. This finding raises the possibility that beliefs about God can mitigate bias against other groups and reduce barriers to peace.

  19. Thinking from God’s perspective decreases biased valuation of the life of a nonbeliever

    Science.gov (United States)

    Ginges, Jeremy; Sheikh, Hammad; Atran, Scott; Argo, Nichole

    2016-01-01

    Religious belief is often thought to motivate violence because it is said to promote norms that encourage tribalism and the devaluing of the lives of nonbelievers. If true, this should be visible in the multigenerational violent conflict between Palestinians and Israelis which is marked by a religious divide. We conducted experiments with a representative sample of Muslim Palestinian youth (n = 555), examining whether thinking from the perspective of Allah (God), who is the ultimate arbitrator of religious belief, changes the relative value of Jewish Israelis’ lives (compared with Palestinian lives). Participants were presented with variants of the classic “trolley dilemma,” in the form of stories where a man can be killed to save the lives of five children who were either Jewish Israeli or Palestinian. They responded from their own perspective and from the perspective of Allah. We find that whereas a large proportion of participants were more likely to endorse saving Palestinian children than saving Jewish Israeli children, this proportion decreased when thinking from the perspective of Allah. This finding raises the possibility that beliefs about God can mitigate bias against other groups and reduce barriers to peace. PMID:26711991

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

    Directory of Open Access Journals (Sweden)

    Tarikul Huda Mazumder

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

  1. Cognitive biases and use of e-government. A behavioral perspective

    Directory of Open Access Journals (Sweden)

    Cayetano Medina-Molina

    2018-05-01

    Full Text Available E-government is conceived as a tool to improve efficiency and effectiveness in the provision of public services. However, in spite of the efforts to achieve a widespread adoption of e-government, it has lower usage rates than expected. Although this fact has been studied from different viewpoints, in the present work the behavioral perspective is presented as an approach that may answer to this challenge. To get it, the relationship between different cognitive biases linked to the SQB (habit, inertia and resistance with the intention (of use for users and continuation for users is analyzed. The data were collected after a qualitative (two group sessions and a quantitative work (923 questionnaires, aimed at two different samples of citizens (non-users and users of e-government. The results confirm the presence of the trend towards the status quo in the use of e-government. Besides, while in the case of non-users of e-government the cognitive biases analyzed are present, leading to delay its use, among the users of e-government habit lacks relevance, so they remain in use as a channel of access to public services.

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

    International Nuclear Information System (INIS)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhongming Zhao

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    2016-08-01

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

  5. Further explorations of the facing bias in biological motion perception: perspective cues, observer sex, and response times.

    Directory of Open Access Journals (Sweden)

    Ben Schouten

    Full Text Available The human visual system has evolved to be highly sensitive to visual information about other persons and their movements as is illustrated by the effortless perception of point-light figures or 'biological motion'. When presented orthographically, a point-light walker is interpreted in two anatomically plausible ways: As 'facing the viewer' or as 'facing away' from the viewer. However, human observers show a 'facing bias': They perceive such a point-light walker as facing towards them in about 70-80% of the cases. In studies exploring the role of social and biological relevance as a possible account for the facing bias, we found a 'figure gender effect': Male point-light figures elicit a stronger facing bias than female point-light figures. Moreover, we also found an 'observer gender effect': The 'figure gender effect' was stronger for male than for female observers. In the present study we presented to 11 males and 11 females point-light walkers of which, very subtly, the perspective information was manipulated by modifying the earlier reported 'perspective technique'. Proportions of 'facing the viewer' responses and reaction times were recorded. Results show that human observers, even in the absence of local shape or size cues, easily pick up on perspective cues, confirming recent demonstrations of high visual sensitivity to cues on whether another person is potentially approaching. We also found a consistent difference in how male and female observers respond to stimulus variations (figure gender or perspective cues that cause variations in the perceived in-depth orientation of a point-light walker. Thus, the 'figure gender effect' is possibly caused by changes in the relative locations and motions of the dots that the perceptual system tends to interpret as perspective cues. Third, reaction time measures confirmed the existence of the facing bias and recent research showing faster detection of approaching than receding biological motion.

  6. Healthcare professionals' use of health clouds: Integrating technology acceptance and status quo bias perspectives.

    Science.gov (United States)

    Hsieh, Pi-Jung

    2015-07-01

    Cloud computing technology has recently been seen as an important milestone in medical informatics development. Despite its great potential, there are gaps in our understanding of how users evaluate change in relation to the health cloud and how they decide to resist it. Integrating technology acceptance and status quo bias perspectives, this study develops an integrated model to explain healthcare professionals' intention to use the health cloud service and their intention to resist it. A field survey was conducted in Taiwan to collect data from healthcare professionals; a structural equation model was used to examine the data. A valid sample of 209 healthcare professionals was collected for data analysis. The results show that healthcare professionals' resistance to the use of the health cloud is the result of regret avoidance, inertia, perceived value, switching costs, and perceived threat. Attitude, subjective norm, and perceived behavior control are shown to have positive and direct effects on healthcare professionals' intention to use the health cloud. The results also indicate a significant negative effect in the relationship between healthcare professionals' intention and resistance to using the health cloud. Our study illustrates the importance of incorporating user resistance in technology acceptance studies in general and in health technology usage studies in particular. This study also identifies key factors for practitioners and hospitals to make adoption decisions in relation to the health cloud. Further, the study provides a useful reference for future studies in this subject field. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Annonaceae substitution rates: a codon model perspective

    Directory of Open Access Journals (Sweden)

    Lars Willem Chatrou

    2014-01-01

    Full Text Available The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these differences has led to inconsistent results when estimating the ages of clades in Annonaceae using molecular dating techniques. We ask whether these differences may be attributed to inappropriate modelling assumptions in the phylogenetic analyses. Specifically, we test for (clade-specific differences in rates of non-synonymous and synonymous substitutions. A high ratio of nonsynonymous to synonymous substitutions may lead to similarity of DNA sequences due to convergence instead of common ancestry, and as a result confound phylogenetic analyses. We use a dataset of three chloroplast genes (rbcL, matK, ndhF for 129 species representative of the family. We find that differences in branch lengths between major clades are not attributable to different rates of non-synonymous and synonymous substitutions. The differences in evolutionary rate between the major clades of Annonaceae pose a challenge for current molecular dating techniques that should be seen as a warning for the interpretation of such results in other organisms.

  8. Phylogenetic inference with weighted codon evolutionary distances.

    Science.gov (United States)

    Criscuolo, Alexis; Michel, Christian J

    2009-04-01

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

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

    Science.gov (United States)

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

    2017-08-21

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    KAUST Repository

    Zhang, Zhang; Li, Jun; Cui, Peng; Ding, Feng; Li, Ang; Townsend, Jeffrey P; Yu, Jun

    2012-01-01

    measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have

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

    Indian Academy of Sciences (India)

    Prosen

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

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

    Science.gov (United States)

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

    2017-12-02

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

  14. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen...... the cell-based immune system is controlled. Bias comes in three forms; ligand-, receptor- and tissue-bias. Biased signaling is increasingly being recognized as playing an important role in contributing to the fine-tuned coordination of immune cell chemotaxis. In the current review we discuss the recent...

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Linial Nathan

    2009-12-01

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

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

    Indian Academy of Sciences (India)

    M. capricolum subsp. capricolum. A. 29.1–54.9. 41.9. ± 3.66. T. 16.2–48.9. 34.0. ± 4.20. C. 5.8–20.3. 10.1. ± 1.95. G. 6.5–29.5. 13.9. ± 2.73. A1. 25.7–59.0. 41.0. ± 4.73. T1. 5–40. 23.0. ± 5.04. C1. 1.6–21.1. 10.0. ± 2.35. G1. 10.5–53.7. 26.0. ± 6.17. A2. 15.7–59.7. 40.0. ± 7.33. T2. 7.0–54.0. 33.0. ± 5.80. C2. 5.6–46.3. 16.0.

  18. Towards a de-biased social psychology: The effects of ideological perspective go beyond politics.

    Science.gov (United States)

    Funder, David C

    2015-01-01

    Reasonable conservatives are in short supply and will not arrive to save social psychology any time soon. The field needs to save itself through de-biasing. The effects of a liberal worldview permeate and distort discussion of many topics that are not overtly political, including behavioral genetics and evolutionary psychology, the fundamental attribution error, and the remarkably persistent consistency controversy.

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

    Directory of Open Access Journals (Sweden)

    Edgar E. Lara-Ramírez

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  2. Correlation matrix for quartet codon usage

    CERN Document Server

    Frappat, L; Sorba, Paul

    2005-01-01

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

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

    Science.gov (United States)

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

    2012-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Aridaman Pandit

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

  5. Not sensitive, yet less biased: A signal detection theory perspective on mindfulness, attention, and recognition memory.

    Science.gov (United States)

    Rosenstreich, Eyal; Ruderman, Lital

    2016-07-01

    The practice of mindfulness has been argued to increase attention control and improve memory performance. However, it was recently suggested that the effect of mindfulness on memory may be due to a shift in response-bias, rather than to an increase in memory-sensitivity. The present study examined the mindfulness-attention-memory triad. Participants filled in the five-facets of mindfulness questionnaire, and completed two recognition blocks; in the first attention was full, whereas in the second attention was divided during the encoding of information. It was found that the facet of non-judging (NJ) moderated the impact of attention on memory, such that responses of high NJ participants were less biased and remained constant even when attention was divided. Facets of mindfulness were not associated with memory sensitivity. These findings suggest that mindfulness may affect memory through decision making processes, rather than through directing attentional resources to the encoding of information. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Indian Academy of Sciences (India)

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

  7. A pancultural perspective on the fading affect bias in autobiographical memory.

    Science.gov (United States)

    Ritchie, Timothy D; Batteson, Tamzin J; Bohn, Annette; Crawford, Matthew T; Ferguson, Georgie V; Schrauf, Robert W; Vogl, Rodney J; Walker, W Richard

    2015-01-01

    The fading affect bias (FAB) refers to the negative affect associated with autobiographical events fading faster than the positive affect associated with such events, a reliable and valid valence effect established by researchers in the USA. The present study examined the idea that the FAB is a ubiquitous emotion regulating phenomenon in autobiographical memory that is present in people from a variety of cultures. We tested for evidence of the FAB by sampling more than 2400 autobiographical event descriptions from 562 participants in 10 cultures around the world. Using variations on a common method, each sample evidenced a FAB: positive affect faded slower than negative affect did. Results suggest that in tandem with local norms and customs, the FAB may foster recovery from negative life events and promote the retention of the positive emotions, within and outside of the USA. We discuss these findings in the context of Keltner and Haidt's levels of analysis theory of emotion and culture.

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

    Science.gov (United States)

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

    2013-06-01

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

  9. Automated design of degenerate codon libraries.

    Science.gov (United States)

    Mena, Marco A; Daugherty, Patrick S

    2005-12-01

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

  10. Universality and Shannon entropy of codon usage

    CERN Document Server

    Frappat, L; Sciarrino, A; Sorba, Paul

    2003-01-01

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

  11. Hand gesture recognition by analysis of codons

    Science.gov (United States)

    Ramachandra, Poornima; Shrikhande, Neelima

    2007-09-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    David J Hauber

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

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

    Directory of Open Access Journals (Sweden)

    Garcia-Vallvé Santiago

    2008-01-01

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

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

    Indian Academy of Sciences (India)

    2013-10-01

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

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

    OpenAIRE

    Moore, Gregory L.; Maranas, Costas D.

    2002-01-01

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

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

    Science.gov (United States)

    2016-09-20

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

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

    OpenAIRE

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

    1994-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mondal U

    2008-01-01

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

  20. Stop Codon Reassignment in the Wild

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-21

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

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

    Directory of Open Access Journals (Sweden)

    Ye Chen

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

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

    Directory of Open Access Journals (Sweden)

    Gabriela Moura

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

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

    Directory of Open Access Journals (Sweden)

    Christopher D Johnston

    2014-09-01

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

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

    Science.gov (United States)

    Dana, Alexandra; Tuller, Tamir

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2004-01-01

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

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

    Science.gov (United States)

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

    2003-06-27

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

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

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal; Křížek, P.

    2012-01-01

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

  9. Explaining financial and prosocial biases in favor of attractive people: Interdisciplinary perspectives from economics, social psychology, and evolutionary psychology.

    Science.gov (United States)

    Maestripieri, Dario; Henry, Andrea; Nickels, Nora

    2017-01-01

    Financial and prosocial biases in favor of attractive adults have been documented in the labor market, in social transactions in everyday life, and in studies involving experimental economic games. According to the taste-based discrimination model developed by economists, attractiveness-related financial and prosocial biases are the result of preferences or prejudices similar to those displayed toward members of a particular sex, racial, ethnic, or religious group. Other explanations proposed by economists and social psychologists maintain that attractiveness is a marker of personality, intelligence, trustworthiness, professional competence, or productivity. Evolutionary psychologists have argued that attractive adults are favored because they are preferred sexual partners. Evidence that stereotypes about attractive people are causally related to financial or prosocial biases toward them is weak or nonexistent. Consistent with evolutionary explanations, biases in favor of attractive women appear to be more consistent or stronger than those in favor of attractive men, and biases are more consistently reported in interactions between opposite-sex than same-sex individuals. Evolutionary explanations also account for increased prosocial behavior in situations in which attractive individuals are simply bystanders. Finally, evolutionary explanations are consistent with the psychological, physiological, and behavioral changes that occur when individuals are exposed to potential mates, which facilitate the expression of courtship behavior and increase the probability of occurrence of mating. Therefore, multiple lines of evidence suggest that mating motives play a more important role in driving financial and prosocial biases toward attractive adults than previously recognized.

  10. Efficient Coproduction of Mannanase and Cellulase by the Transformation of a Codon-Optimized Endomannanase Gene from Aspergillus niger into Trichoderma reesei.

    Science.gov (United States)

    Sun, Xianhua; Xue, Xianli; Li, Mengzhu; Gao, Fei; Hao, Zhenzhen; Huang, Huoqing; Luo, Huiying; Qin, Lina; Yao, Bin; Su, Xiaoyun

    2017-12-20

    Cellulase and mannanase are both important enzyme additives in animal feeds. Expressing the two enzymes simultaneously within one microbial host could potentially lead to cost reductions in the feeding of animals. For this purpose, we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of Trichoderma reesei. By comparing the free energies and the local structures of the nucleotide sequences, one optimized sequence was finally selected and transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon-optimized gene was expressed to a higher level than the original one. Further expressing the codon-optimized gene in a mutated T. reesei strain through fed-batch cultivation resulted in coproduction of cellulase and mannanase up to 1376 U·mL -1 and 1204 U·mL -1 , respectively.

  11. Potential negative effects of perspective-taking efforts in the context of close relationships: increased bias and reduced satisfaction.

    Science.gov (United States)

    Vorauer, Jacquie D; Sucharyna, Tamara A

    2013-01-01

    Three experiments demonstrated that trying to appreciate a close other's unique point of view (imagine-other perspective taking) increases the extent to which individuals overestimate their own transparency to the close other, that is, how many of their values, preferences, traits, and feelings are readily apparent to him or her. Trying to be objective and pay careful attention to cues from a close other, which inhibits perspective taking, instead had the opposite effect. Mediation analyses suggested that increased focus on the self as an object of evaluation contributed to the positive effect of imagine-other perspective taking on perceived transparency, and decreased focus on the self as an object of evaluation contributed to the negative effect of trying to be objective on these judgments. These effects on perceived transparency had important implications for relationship well-being: Enhanced perceived transparency of negative feelings prompted by imagine-other perspective taking during a back-and-forth exchange with a romantic partner led to systematic discrepancies between individuals' own and their partner's experience of the exchange and reduced relationship satisfaction; trying to be objective instead reduced perceived transparency and thereby increased satisfaction. Notably, initial closeness with another person enhanced rather than tempered the egocentric effects of perspective taking. Taken together, these results suggest that positive motivations to nurture a close relationship and be sensitive to a loved one might sometimes be better channeled toward paying closer attention to his or her behavior than toward perspective taking.

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

    Directory of Open Access Journals (Sweden)

    Fei Xia

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Laura Frigotto

    2015-05-01

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

  15. Stuck in the past: negative bias, explanatory style, temporal order, and evaluative perspectives in life narratives of clinically depressed individuals.

    Science.gov (United States)

    Habermas, Tilmann; Ott, Lisa-M; Schubert, Merve; Schneider, Beatrix; Pate, Anna

    2008-01-01

    This study attempted to replicate negative bias and depressive explanatory style in depression using life narratives. The two central aspects of narrative, temporal succession and evaluation, were also explored. These aspects were tested for the first time using entire life narratives of 17 depressed inpatients and non-depressed controls matched for sex and educational level. Negative bias and depressive explanatory style were replicated as typical for the depressed group. Life narratives of depressed patients also deviated more from a linear temporal order and compared less frequently the past with the present. Contrary to expectations, the depressed did not differ in the overall frequency of evaluations. However, they used more past than present evaluations and more experience-near evaluations than cognitive evaluations, suggesting that they are more immersed in past experiences. It is concluded that negative bias and depressive explanatory style can be found also in a naturalistic narrative measure, and that depression affects the two major aspects of narrative. It is argued that life narratives, as measures close to everyday clinical practice and as the most encompassing form of self-representation, should complement more experimental procedures in the study of cognitive and communicative processes in psychopathology. 2007 Wiley-Liss, Inc.

  16. Synonymous codon usage analysis of hand, foot and mouth disease viruses: A comparative study on coxsackievirus A6, A10, A16, and enterovirus 71 from 2008 to 2015.

    Science.gov (United States)

    Su, Weiheng; Li, Xue; Chen, Meili; Dai, Wenwen; Sun, Shiyang; Wang, Shuai; Sheng, Xin; Sun, Shixiang; Gao, Chen; Hou, Ali; Zhou, Yan; Sun, Bo; Gao, Feng; Xiao, Jingfa; Zhang, Zhewen; Jiang, Chunlai

    2017-09-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) have been considered major pathogens of hand, foot and mouth disease (HFMD) throughout the world for decades. In recent years, coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) have raised attention as two other serious pathogens of HFMD. The present study focused on the synonymous codon usage of four viruses isolated from 2008 to 2015, with particular attention on P1 (encoding capsid proteins) and P2-P3 regions (both encoding non-structural proteins) in the genomic RNA. Relative synonymous codon usage, effective number of codons, neutrality and correspondence were analyzed. The results indicated that these viruses prefer A/T at the third position in codons rather than G/C. The most frequent codons of 4 essential and 2 semi-essential amino acids, as well as a key amino acid of metabolic junctions (Glu) used in the four viruses are also the most frequently used in humans. Effective number of codons (ENC) values indicated weak codon usage bias in all the viruses. Relatively, the force of mutation pressure in the P1 region was found to be stronger than that in the P2-P3 region, and this force in the P1 region of CVA6 and EV71 was stronger than that of CVA10 and A16. The neutrality analysis results implied that mutation pressure plays a minor role in shaping codon bias of these viruses. Correspondence analysis indicated that the codon usage of EV71 strains varied much more than that of other viruses. In conclusion, the present study provides novel and comparative insight into the evolution of HFMD pathogens at the codon level. Copyright © 2017. Published by Elsevier B.V.

  17. AUG is the only initiation codon in eukaryotes

    Energy Technology Data Exchange (ETDEWEB)

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

    1980-01-01

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

  18. Same-strand overlapping genes in bacteria: compositional determinants of phase bias

    Directory of Open Access Journals (Sweden)

    Landan Giddy

    2008-08-01

    Full Text Available Abstract Background Same-strand overlapping genes may occur in frameshifts of one (phase 1 or two nucleotides (phase 2. In previous studies of bacterial genomes, long phase-1 overlaps were found to be more numerous than long phase-2 overlaps. This bias was explained by either genomic location or an unspecified selection advantage. Models that focused on the ability of the two genes to evolve independently did not predict this phase bias. Here, we propose that a purely compositional model explains the phase bias in a more parsimonious manner. Same-strand overlapping genes may arise through either a mutation at the termination codon of the upstream gene or a mutation at the initiation codon of the downstream gene. We hypothesized that given these two scenarios, the frequencies of initiation and termination codons in the two phases may determine the number for overlapping genes. Results We examined the frequencies of initiation- and termination-codons in the two phases, and found that termination codons do not significantly differ between the two phases, whereas initiation codons are more abundant in phase 1. We found that the primary factors explaining the phase inequality are the frequencies of amino acids whose codons may combine to form start codons in the two phases. We show that the frequencies of start codons in each of the two phases, and, hence, the potential for the creation of overlapping genes, are determined by a universal amino-acid frequency and species-specific codon usage, leading to a correlation between long phase-1 overlaps and genomic GC content. Conclusion Our model explains the phase bias in same-strand overlapping genes by compositional factors without invoking selection. Therefore, it can be used as a null model of neutral evolution to test selection hypotheses concerning the evolution of overlapping genes. Reviewers This article was reviewed by Bill Martin, Itai Yanai, and Mikhail Gelfand.

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

    Science.gov (United States)

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

    1994-05-11

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

  20. Codon and amino acid usage in two major human pathogens of genus Bartonella--optimization between replicational-transcriptional selection, translational control and cost minimization.

    Science.gov (United States)

    Das, Sabyasachi; Paul, Sandip; Chatterjee, Sanjib; Dutta, Chitra

    2005-01-01

    Intra-genomic variation in synonymous codon and amino acid usage in two human pathogens Bartonella henselae and B. quintana has been carried out through multivariate analysis. Asymmetric mutational bias, coupled with replicational-transcriptional selection, has been identified as the prime selection force behind synonymous codon selection--a characteristic of the genus Bartonella, not exhibited by any other alpha-proteobacterial genome. Distinct codon usage patterns and low synonymous divergence values between orthologous sequences of highly expressed genes from the two Bartonella species indicate that there exists a residual intra-strand synonymous codon bias in the highly expressed genes, possibly operating at the level of translation. In the case of amino acid usage, the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact, while strand-specific mutational pressure and gene expressivity strongly influence the inter-strand variations. In both species under study, the highly expressed gene products tend not to contain heavy and/or aromatic residues, following the cost-minimization hypothesis in spite of their intracellular lifestyle. The codon and amino acid usage in these two human pathogens are, therefore, consequences of a complex balance between replicational-transcriptional selection, translational control, protein hydropathy and cost minimization.

  1. Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Dai R

    2014-03-01

    Full Text Available Rujuan Dai, S Ansar Ahmed Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Abstract: Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs, is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex

  2. Project Management in Behavioural Perspective – Cognitive Biases in the Formulation of the Aim of the Project

    Directory of Open Access Journals (Sweden)

    Kiełczewski Dariusz

    2016-09-01

    Full Text Available The article contains a behavioural analysis of the aim-formulating stage of the project. The purpose of the article is to point out that in the process of formulating the aim of the project, it comes to such decision-making situations which favour heuristic thinking. The article presents the results of the secondary research. As a result of verified theory, according to which in the process of formulating the aim of the project, the interference in decision-making processes may occur on the part of the heuristics and the resulting cognitive biases.

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

    African Journals Online (AJOL)

    Administrator

    2011-09-12

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

  4. Polymorphism at codon 36 of the p53 gene.

    Science.gov (United States)

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

    1994-01-01

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

  5. Positive selection for unpreferred codon usage in eukaryotic genomes

    Directory of Open Access Journals (Sweden)

    Galagan James E

    2007-07-01

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

  6. Time perspective, optimistic bias, and self-control among different statuses of university smokers in China: a cross-sectional study.

    Science.gov (United States)

    Xu, Ying; Yang, Yang; Ma, Xiao

    2018-01-09

    Risk behavior often seems 'self-defeating' to the observers. Most people understand the basic health-related knowledge, but some of them still choose to continue risk behaviors, especially for the young. This study aimed to examine time perspective, optimism bias and self control correlated with smoking behavior in Chinese college students. A cross-sectional survey enrolling 3016 university students in Chengdu City, Sichuan Province, China. Influence Factors were identified using multiple logistic regression analyses. Prevalence of current smoking was 20.92% (631 smokers), including 272 daily smokers (9.02%) and 359 non-daily smokers (11.90%). Future-oriented time perspective, general capacity for self-discipline, reliability and ethnicity were protective factors of smoking behavior. Possibility of self-suffering diseases and gender were risk factors of smoking behavior. Smoking in University of Chengdu, China is a severe problem. Results in this research have suggested that irrespective of the smoking level, improving health-related knowledge, time management awareness and self-control ability may contribute to reducing the prevalence of smoking behavior.

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

    Directory of Open Access Journals (Sweden)

    Dinglin Zhang

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Àlbert Rafels-Ybern

    2015-07-01

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

  10. GENDER BIAS AND CHILD LABOR: SPAIN, LATIN AMERICA AND DEVELOPING COUNTRIES FROM A LONG-TERM COMPARATIVE PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Enriqueta Camps-Cura

    2016-11-01

    Full Text Available In this paper, several historical scenarios are compared, each very different to the each other in both institutional and geographical terms. What they have in common is the relative poverty of part of the population. This approach allows combining micro historical analysis (in the Catalan case with a macro comparative approach in developing countries. Through these micro historical and macro regression analyses we obtain the result that adult women’s skills and real wages are a key factor when we wish to explain the patterns of child labor. While female real wages increased sharply in 19th century Catalonia, we obtain very different results in the case of developing countries. This gender bias is identified as one of the very significant effects of human capital which held by women and helps to explain why in some cases children continue to work and also why some parts of the world continue to be poor according to our regression analysis.

  11. A biased historical perspective of women in the engineering field at Dryden from 1946 to November 1992

    Science.gov (United States)

    Powers, Sheryll Goecke

    1994-01-01

    Being a woman in engineering, and in particular, being the woman with the dubious distinction of having the most years at Dryden, gives the author a long-term perspective on the women who worked in the engineering field and their working environment. The working environment for the women was influenced by two main factors. One factor was the Dryden's growth of 14 persons (2 of them women) at the end of 1946 to the present size. The other factor was the need for programming knowledge when the digital computers came into use. Women have been involved with flight research at Dryden since the days of the first transonic and supersonic airplanes. This paper uses available records, along with memory, to document the number of women in engineering at Dryden, to comment about observed trends, and to make personal observations.

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

    Science.gov (United States)

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

    2017-03-17

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

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

    Science.gov (United States)

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-07

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

  14. P-value based visualization of codon usage data

    Directory of Open Access Journals (Sweden)

    Fricke Wolfgang

    2006-06-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  16. Provider perspectives on PrEP for adolescent girls and young women in Tanzania: The role of provider biases and quality of care.

    Directory of Open Access Journals (Sweden)

    Nanlesta Pilgrim

    Full Text Available Oral pre-exposure prophylaxis (PrEP has the potential to reduce HIV acquisition among adolescent girls and young women (AGYW in sub-Saharan Africa. However, health care providers' (HCPs perspectives and interactions with potential clients can substantially influence effective provision of quality health services. We examine if HCPs' knowledge, attitude, and skills, as well as their perceptions of facility readiness to provide PrEP are associated with their willingness to provide PrEP to AGYW at high risk of HIV in Tanzania.A self-administered questionnaire was given to 316 HCPs from 74 clinics in two districts and 24 HCPs participated in follow-up in-depth interviews (IDIs. We conducted bivariate and multivariable Poisson regression to assess factors associated with willingness to provide PrEP to AGYW. Thematic content analysis was used to analyze the IDIs, which expanded upon the quantitative results.Few HCPs (3.5% had prior PrEP knowledge, but once informed, 61.1% were willing to prescribe PrEP to AGYW. Higher negative attitudes toward adolescent sexuality and greater concerns about behavioral disinhibition due to PrEP use were associated with lower willingness to prescribe PrEP. Qualitatively, HCPs acknowledged that biases, rooted in cultural norms, often result in stigmatizing and discriminatory care toward AGYW, a potential barrier for PrEP provision. However, better training to provide HIV services was associated with greater willingness to prescribe PrEP. Conversely, HCPs feared the potential negative impact of PrEP on the provision of existing HIV services (e.g., overburdened staff, and suggested the integration of PrEP into non-HIV services and the use of paramedical professionals to facilitate PrEP provision.Preparing for PrEP introduction requires more than solely training HCPs on the clinical aspects of providing PrEP. It requires a two-pronged strategy: addressing HCPs' biases regarding sexual health services to AGYW; and preparing

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

    African Journals Online (AJOL)

    Yomi

    2012-02-16

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

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

    Science.gov (United States)

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

    2012-09-10

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

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

    African Journals Online (AJOL)

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

  20. TP53 codon 72 polymorphism in pigmentary phenotypes

    Indian Academy of Sciences (India)

    2012-01-20

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

  1. Codon usage determines translation rate in Escherichia coli

    DEFF Research Database (Denmark)

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

    1989-01-01

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

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

    Indian Academy of Sciences (India)

    Unknown

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

  3. The mitochondrial genome sequence of the ciliate Paramecium caudatum reveals a shift in nucleotide composition and codon usage within the genus Paramecium

    Directory of Open Access Journals (Sweden)

    Berendonk Thomas U

    2011-05-01

    Full Text Available Abstract Background Despite the fact that the organization of the ciliate mitochondrial genome is exceptional, only few ciliate mitochondrial genomes have been sequenced until today. All ciliate mitochondrial genomes are linear. They are 40 kb to 47 kb long and contain some 50 tightly packed genes without introns. Earlier studies documented that the mitochondrial guanine + cytosine contents are very different between Paramecium tetraurelia and all studied Tetrahymena species. This raises the question of whether the high mitochondrial G+C content observed in P. tetraurelia is a characteristic property of Paramecium mtDNA, or whether it is an exception of the ciliate mitochondrial genomes known so far. To test this question, we determined the mitochondrial genome sequence of Paramecium caudatum and compared the gene content and sequence properties to the closely related P. tetraurelia. Results The guanine + cytosine content of the P. caudatum mitochondrial genome was significantly lower than that of P. tetraurelia (22.4% vs. 41.2%. This difference in the mitochondrial nucleotide composition was accompanied by significantly different codon usage patterns in both species, i.e. within P. caudatum clearly A/T ending codons dominated, whereas for P. tetraurelia the synonymous codons were more balanced with a higher number of G/C ending codons. Further analyses indicated that the nucleotide composition of most members of the genus Paramecium resembles that of P. caudatum and that the shift observed in P. tetraurelia is restricted to the P. aurelia species complex. Conclusions Surprisingly, the codon usage bias in the P. caudatum mitochondrial genome, exemplified by the effective number of codons, is more similar to the distantly related T. pyriformis and other single-celled eukaryotes such as Chlamydomonas, than to the closely related P. tetraurelia. These differences in base composition and codon usage bias were, however, not reflected in the amino

  4. Sympathetic bias.

    Science.gov (United States)

    Levy, David M; Peart, Sandra J

    2008-06-01

    We wish to deal with investigator bias in a statistical context. We sketch how a textbook solution to the problem of "outliers" which avoids one sort of investigator bias, creates the temptation for another sort. We write down a model of the approbation seeking statistician who is tempted by sympathy for client to violate the disciplinary standards. We give a simple account of one context in which we might expect investigator bias to flourish. Finally, we offer tentative suggestions to deal with the problem of investigator bias which follow from our account. As we have given a very sparse and stylized account of investigator bias, we ask what might be done to overcome this limitation.

  5. Codon Distribution in Error-Detecting Circular Codes

    Directory of Open Access Journals (Sweden)

    Elena Fimmel

    2016-03-01

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

  6. Codon Distribution in Error-Detecting Circular Codes.

    Science.gov (United States)

    Fimmel, Elena; Strüngmann, Lutz

    2016-03-15

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

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

    Directory of Open Access Journals (Sweden)

    Jian-hua Zhou

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

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

    DEFF Research Database (Denmark)

    Mitarai, Namiko; Pedersen, Steen

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wayne Delport

    2010-08-01

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

  10. Journal bias or author bias?

    Science.gov (United States)

    Harris, Ian

    2016-01-01

    I read with interest the comment by Mark Wilson in the Indian Journal of Medical Ethics regarding bias and conflicts of interest in medical journals. Wilson targets one journal (the New England Journal of Medicine: NEJM) and one particular "scandal" to make his point that journals' decisions on publication are biased by commercial conflicts of interest (CoIs). It is interesting that he chooses the NEJM which, by his own admission, had one of the strictest CoI policies and had published widely on this topic. The feeling is that if the NEJM can be guilty, they can all be guilty.

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

    Science.gov (United States)

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

    2018-01-25

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

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

    Science.gov (United States)

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

    2018-04-01

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

  13. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression

    International Nuclear Information System (INIS)

    Nguyen, Kim-Lien; Llano, Manuel; Akari, Hirofumi; Miyagi, Eri; Poeschla, Eric M.; Strebel, Klaus; Bour, Stephan

    2004-01-01

    Two HIV-1 accessory proteins, Vpu and Vif, are notoriously difficult to express autonomously in the absence of the viral Tat and Rev proteins. We examined whether the codon bias observed in the vpu and vif genes relative to highly expressed human genes contributes to the Rev dependence and low expression level outside the context of the viral genome. The entire vpu gene as well as the 5' half of the vif gene were codon optimized and the resulting open reading frames (ORFs) (vphu and hvif, respectively) were cloned in autonomous expression vectors under the transcriptional control of the CMV promoter. Codon optimization efficiently removed the expression block observed in the native genes and allowed high levels of Rev- and Tat-independent expression of Vpu and Vif. Most of the higher protein levels detected are accounted for by enhanced steady-state levels of the mRNA encoding the optimized species. Nuclear run-on experiments show for the first time that codon optimization has no effect on the rate of transcriptional initiation or elongation of the vphu mRNA. Instead, optimization of the vpu gene was found to stabilize the vphu mRNA in the nucleus and enhance its export to the cytoplasm. This was achieved by allowing the optimized mRNA to use a new CRM1-independent nuclear export pathway. This work provides a better understanding of the molecular mechanisms underlying the process of codon optimization and introduces novel tools to study the biological functions of the Vpu and Vif proteins independently of other viral proteins

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

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

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

  15. Biased Supervision

    OpenAIRE

    Josse Delfgaauw; Michiel Souverijn

    2014-01-01

    markdownabstract__Abstract__ When verifiable performance measures are imperfect, organizations often resort to subjective performance pay. This may give supervisors the power to direct employees towards tasks that mainly benefit the supervisor rather than the organization. We cast a principal-supervisor-agent model in a multitask setting, where the supervisor has an intrinsic preference towards specific tasks. We show that subjective performance pay based on evaluation by a biased supervisor ...

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2017-09-29

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

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

    Directory of Open Access Journals (Sweden)

    Wei Liu

    2017-08-01

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

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

    Science.gov (United States)

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

    2017-08-29

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-10-01

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

  2. Perspective

    DEFF Research Database (Denmark)

    Kussmann, Martin; Morine, Melissa J; Hager, Jörg

    2013-01-01

    We review here the status of human type 2 diabetes studies from a genetic, epidemiological, and clinical (intervention) perspective. Most studies limit analyses to one or a few omic technologies providing data of components of physiological processes. Since all chronic diseases are multifactorial...... at different time points along this longitudinal investigation are performed with a comprehensive set of omics platforms. These data sets are generated in a biological context, rather than biochemical compound class-driven manner, which we term "systems omics."...

  3. Codon and amino-acid distribution in DNA

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  4. Protein evolution via amino acid and codon elimination

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

    Santos, José; Monteagudo, Angel

    2011-02-21

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

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

    Directory of Open Access Journals (Sweden)

    Monteagudo Ángel

    2011-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Wang Tzu-Ling

    2010-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiao-Tang Kong

    2001-01-01

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

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

    Science.gov (United States)

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

    2016-02-19

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

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

    Science.gov (United States)

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

    2016-07-01

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

  13. Bias against research on gender bias.

    Science.gov (United States)

    Cislak, Aleksandra; Formanowicz, Magdalena; Saguy, Tamar

    2018-01-01

    The bias against women in academia is a documented phenomenon that has had detrimental consequences, not only for women, but also for the quality of science. First, gender bias in academia affects female scientists, resulting in their underrepresentation in academic institutions, particularly in higher ranks. The second type of gender bias in science relates to some findings applying only to male participants, which produces biased knowledge. Here, we identify a third potentially powerful source of gender bias in academia: the bias against research on gender bias. In a bibliometric investigation covering a broad range of social sciences, we analyzed published articles on gender bias and race bias and established that articles on gender bias are funded less often and published in journals with a lower Impact Factor than articles on comparable instances of social discrimination. This result suggests the possibility of an underappreciation of the phenomenon of gender bias and related research within the academic community. Addressing this meta-bias is crucial for the further examination of gender inequality, which severely affects many women across the world.

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

    Science.gov (United States)

    Alkalaeva, Elena; Mikhailova, Tatiana

    2017-03-01

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

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

    OpenAIRE

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

    2014-01-01

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

  16. The Purine Bias of Coding Sequences is Determined by Physicochemical Constraints on Proteins.

    Science.gov (United States)

    Ponce de Leon, Miguel; de Miranda, Antonio Basilio; Alvarez-Valin, Fernando; Carels, Nicolas

    2014-01-01

    For this report, we analyzed protein secondary structures in relation to the statistics of three nucleotide codon positions. The purpose of this investigation was to find which properties of the ribosome, tRNA or protein level, could explain the purine bias (Rrr) as it is observed in coding DNA. We found that the Rrr pattern is the consequence of a regularity (the codon structure) resulting from physicochemical constraints on proteins and thermodynamic constraints on ribosomal machinery. The physicochemical constraints on proteins mainly come from the hydropathy and molecular weight (MW) of secondary structures as well as the energy cost of amino acid synthesis. These constraints appear through a network of statistical correlations, such as (i) the cost of amino acid synthesis, which is in favor of a higher level of guanine in the first codon position, (ii) the constructive contribution of hydropathy alternation in proteins, (iii) the spatial organization of secondary structure in proteins according to solvent accessibility, (iv) the spatial organization of secondary structure according to amino acid hydropathy, (v) the statistical correlation of MW with protein secondary structures and their overall hydropathy, (vi) the statistical correlation of thymine in the second codon position with hydropathy and the energy cost of amino acid synthesis, and (vii) the statistical correlation of adenine in the second codon position with amino acid complexity and the MW of secondary protein structures. Amino acid physicochemical properties and functional constraints on proteins constitute a code that is translated into a purine bias within the coding DNA via tRNAs. In that sense, the Rrr pattern within coding DNA is the effect of information transfer on nucleotide composition from protein to DNA by selection according to the codon positions. Thus, coding DNA structure and ribosomal machinery co-evolved to minimize the energy cost of protein coding given the functional

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

    Directory of Open Access Journals (Sweden)

    Jerusa Smid

    2013-07-01

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

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

    DEFF Research Database (Denmark)

    Sørensen, M.A.; Pedersen, Steen

    1991-01-01

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

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

    Science.gov (United States)

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

    2017-11-14

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

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

    Science.gov (United States)

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

    2018-02-01

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

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

    Science.gov (United States)

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

    2018-04-18

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

  2. Rapid Evolution of Ovarian-Biased Genes in the Yellow Fever Mosquito (Aedes aegypti).

    Science.gov (United States)

    Whittle, Carrie A; Extavour, Cassandra G

    2017-08-01

    Males and females exhibit highly dimorphic phenotypes, particularly in their gonads, which is believed to be driven largely by differential gene expression. Typically, the protein sequences of genes upregulated in males, or male-biased genes, evolve rapidly as compared to female-biased and unbiased genes. To date, the specific study of gonad-biased genes remains uncommon in metazoans. Here, we identified and studied a total of 2927, 2013, and 4449 coding sequences (CDS) with ovary-biased, testis-biased, and unbiased expression, respectively, in the yellow fever mosquito Aedes aegypti The results showed that ovary-biased and unbiased CDS had higher nonsynonymous to synonymous substitution rates (dN/dS) and lower optimal codon usage (those codons that promote efficient translation) than testis-biased genes. Further, we observed higher dN/dS in ovary-biased genes than in testis-biased genes, even for genes coexpressed in nonsexual (embryo) tissues. Ovary-specific genes evolved exceptionally fast, as compared to testis- or embryo-specific genes, and exhibited higher frequency of positive selection. Genes with ovary expression were preferentially involved in olfactory binding and reception. We hypothesize that at least two potential mechanisms could explain rapid evolution of ovary-biased genes in this mosquito: (1) the evolutionary rate of ovary-biased genes may be accelerated by sexual selection (including female-female competition or male-mate choice) affecting olfactory genes during female swarming by males, and/or by adaptive evolution of olfactory signaling within the female reproductive system ( e.g. , sperm-ovary signaling); and/or (2) testis-biased genes may exhibit decelerated evolutionary rates due to the formation of mating plugs in the female after copulation, which limits male-male sperm competition. Copyright © 2017 by the Genetics Society of America.

  3. Combination of biased forecasts: Bias correction or bias based weights?

    OpenAIRE

    Wenzel, Thomas

    1999-01-01

    Most of the literature on combination of forecasts deals with the assumption of unbiased individual forecasts. Here, we consider the case of biased forecasts and discuss two different combination techniques resulting in an unbiased forecast. On the one hand we correct the individual forecasts, and on the other we calculate bias based weights. A simulation study gives some insight in the situations where we should use the different methods.

  4. Evolutionary rates at codon sites may be used to align sequences and infer protein domain function

    Directory of Open Access Journals (Sweden)

    Hazelhurst Scott

    2010-03-01

    Full Text Available Abstract Background Sequence alignments form part of many investigations in molecular biology, including the determination of phylogenetic relationships, the prediction of protein structure and function, and the measurement of evolutionary rates. However, to obtain meaningful results, a significant degree of sequence similarity is required to ensure that the alignments are accurate and the inferences correct. Limitations arise when sequence similarity is low, which is particularly problematic when working with fast-evolving genes, evolutionary distant taxa, genomes with nucleotide biases, and cases of convergent evolution. Results A novel approach was conceptualized to address the "low sequence similarity" alignment problem. We developed an alignment algorithm termed FIRE (Functional Inference using the Rates of Evolution, which aligns sequences using the evolutionary rate at codon sites, as measured by the dN/dS ratio, rather than nucleotide or amino acid residues. FIRE was used to test the hypotheses that evolutionary rates can be used to align sequences and that the alignments may be used to infer protein domain function. Using a range of test data, we found that aligning domains based on evolutionary rates was possible even when sequence similarity was very low (for example, antibody variable regions. Furthermore, the alignment has the potential to infer protein domain function, indicating that domains with similar functions are subject to similar evolutionary constraints. These data suggest that an evolutionary rate-based approach to sequence analysis (particularly when combined with structural data may be used to study cases of convergent evolution or when sequences have very low similarity. However, when aligning homologous gene sets with sequence similarity, FIRE did not perform as well as the best traditional alignment algorithms indicating that the conventional approach of aligning residues as opposed to evolutionary rates remains the

  5. Insights on the evolution of metabolic networks of unicellular translationally biased organisms from transcriptomic data and sequence analysis.

    Science.gov (United States)

    Carbone, Alessandra; Madden, Richard

    2005-10-01

    Codon bias is related to metabolic functions in translationally biased organisms, and two facts are argued about. First, genes with high codon bias describe in meaningful ways the metabolic characteristics of the organism; important metabolic pathways corresponding to crucial characteristics of the lifestyle of an organism, such as photosynthesis, nitrification, anaerobic versus aerobic respiration, sulfate reduction, methanogenesis, and others, happen to involve especially biased genes. Second, gene transcriptional levels of sets of experiments representing a significant variation of biological conditions strikingly confirm, in the case of Saccharomyces cerevisiae, that metabolic preferences are detectable by purely statistical analysis: the high metabolic activity of yeast during fermentation is encoded in the high bias of enzymes involved in the associated pathways, suggesting that this genome was affected by a strong evolutionary pressure that favored a predominantly fermentative metabolism of yeast in the wild. The ensemble of metabolic pathways involving enzymes with high codon bias is rather well defined and remains consistent across many species, even those that have not been considered as translationally biased, such as Helicobacter pylori, for instance, reveal some weak form of translational bias for this genome. We provide numerical evidence, supported by experimental data, of these facts and conclude that the metabolic networks of translationally biased genomes, observable today as projections of eons of evolutionary pressure, can be analyzed numerically and predictions of the role of specific pathways during evolution can be derived. The new concepts of Comparative Pathway Index, used to compare organisms with respect to their metabolic networks, and Evolutionary Pathway Index, used to detect evolutionarily meaningful bias in the genetic code from transcriptional data, are introduced.

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

    Directory of Open Access Journals (Sweden)

    Aghil Esmaeili-Bandboni

    2017-11-01

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

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

    Science.gov (United States)

    Engqvist, Martin K M; Nielsen, Jens

    2015-08-21

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

  8. Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda

    Directory of Open Access Journals (Sweden)

    Mun Hua Tan

    2017-03-01

    Full Text Available Background Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters and Caridea (true shrimps are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information. Methods Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements. Results We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders. Discussion Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.

  9. Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.

    Directory of Open Access Journals (Sweden)

    Tapani Hovi

    Full Text Available Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2 were compared to those of type 1 and type 3 wild poliovirus (WPV lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv bias and strikingly lower Ts/Tv rate ratios at the 2(nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (cVDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

  10. Media Bias: Context, Redundancy, and Critical Threshold as Cultural Factor.

    Science.gov (United States)

    Becker, Samuel L.

    Bias in mass communication can be defined as interpretation based on factors that are independent of the original information, or as shaping the meaning of information according to the context in which it is placed. Although research has explored the concept of bias from a number of perspectives, its subtle manifestations can be understood best by…

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

    Science.gov (United States)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  14. Positioning of Weight Bias: Moving towards Social Justice.

    Science.gov (United States)

    Nutter, Sarah; Russell-Mayhew, Shelly; Alberga, Angela S; Arthur, Nancy; Kassan, Anusha; Lund, Darren E; Sesma-Vazquez, Monica; Williams, Emily

    2016-01-01

    Weight bias is a form of stigma with detrimental effects on the health and wellness of individuals with large bodies. Researchers from various disciplines have recognized weight bias as an important topic for public health and for professional practice. To date, researchers from various areas have approached weight bias from independent perspectives and from differing theoretical orientations. In this paper, we examined the similarities and differences between three perspectives (i.e., weight-centric, non-weight-centric (health-centric), and health at every size) used to understand weight bias and approach weight bias research with regard to (a) language about people with large bodies, (b) theoretical position, (c) identified consequences of weight bias, and (d) identified influences on weight-based social inequity. We suggest that, despite differences, each perspective acknowledges the negative influences that position weight as being within individual control and the negative consequences of weight bias. We call for recognition and discussion of weight bias as a social justice issue in order to change the discourse and professional practices extended towards individuals with large bodies. We advocate for an emphasis on social justice as a uniting framework for interdisciplinary research on weight bias.

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

    NARCIS (Netherlands)

    van Hemert, Formijn; Berkhout, Ben

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Friis, Carsten; Juncker, Agnieszka

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Indian Academy of Sciences (India)

    Pankaj Alone

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  1. Amino Acid Usage Is Asymmetrically Biased in AT- and GC-Rich Microbial Genomes

    DEFF Research Database (Denmark)

    Bohlin, Jon; Brynildsrud, Ola Brønstad; Vesth, Tammi Camilla

    2013-01-01

    frequencies were distributed in over 2000 microbial genomes and how these distributions were affected by base compositional changes. In addition, we wanted to know how genome-wide amino acid usage was biased in the different genomes and how changes to base composition and mutations affected this bias...... purifying selection than genomes with higher AAUB. Conclusion: Genomic base composition has a substantial effect on both amino acid- and codon frequencies in bacterial genomes. While phylogeny influenced amino acid usage more in GC-rich genomes, AT-content was driving amino acid usage in AT-rich genomes. We...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Erik Hallengren

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

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

    Science.gov (United States)

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

    2009-04-21

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

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

  7. CPI Bias in Korea

    Directory of Open Access Journals (Sweden)

    Chul Chung

    2007-12-01

    Full Text Available We estimate the CPI bias in Korea by employing the approach of Engel’s Law as suggested by Hamilton (2001. This paper is the first attempt to estimate the bias using Korean panel data, Korean Labor and Income Panel Study(KLIPS. Following Hamilton’s model with non­linear specification correction, our estimation result shows that the cumulative CPI bias over the sample period (2000-2005 was 0.7 percent annually. This CPI bias implies that about 21 percent of the inflation rate during the period can be attributed to the bias. In light of purchasing power parity, we provide an interpretation of the estimated bias.

  8. Biased Gene Conversion and GC-Content Evolution in the Coding Sequences of Reptiles and Vertebrates

    Science.gov (United States)

    Figuet, Emeric; Ballenghien, Marion; Romiguier, Jonathan; Galtier, Nicolas

    2015-01-01

    Mammalian and avian genomes are characterized by a substantial spatial heterogeneity of GC-content, which is often interpreted as reflecting the effect of local GC-biased gene conversion (gBGC), a meiotic repair bias that favors G and C over A and T alleles in high-recombining genomic regions. Surprisingly, the first fully sequenced nonavian sauropsid (i.e., reptile), the green anole Anolis carolinensis, revealed a highly homogeneous genomic GC-content landscape, suggesting the possibility that gBGC might not be at work in this lineage. Here, we analyze GC-content evolution at third-codon positions (GC3) in 44 vertebrates species, including eight newly sequenced transcriptomes, with a specific focus on nonavian sauropsids. We report that reptiles, including the green anole, have a genome-wide distribution of GC3 similar to that of mammals and birds, and we infer a strong GC3-heterogeneity to be already present in the tetrapod ancestor. We further show that the dynamic of coding sequence GC-content is largely governed by karyotypic features in vertebrates, notably in the green anole, in agreement with the gBGC hypothesis. The discrepancy between third-codon positions and noncoding DNA regarding GC-content dynamics in the green anole could not be explained by the activity of transposable elements or selection on codon usage. This analysis highlights the unique value of third-codon positions as an insertion/deletion-free marker of nucleotide substitution biases that ultimately affect the evolution of proteins. PMID:25527834

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

  11. Sampler bias -- Phase 1

    International Nuclear Information System (INIS)

    Blanchard, R.J.

    1995-01-01

    This documents Phase 1 determinations on sampler induced bias for four sampler types used in tank characterization. Each sampler, grab sampler or bottle-on-a-string, auger sampler, sludge sampler and universal sampler, is briefly discussed and their physical limits noted. Phase 2 of this document will define additional testing and analysis to further define Sampler Bias

  12. Photovoltaic Bias Generator

    Science.gov (United States)

    2018-02-01

    Department of the Army position unless so designated by other authorized documents. Citation of manufacturer’s or trade names does not constitute an... Interior view of the photovoltaic bias generator showing wrapped-wire side of circuit board...3 Fig. 4 Interior view of the photovoltaic bias generator showing component side of circuit board

  13. Biases in categorization

    NARCIS (Netherlands)

    Das-Smaal, E.A.

    1990-01-01

    On what grounds can we conclude that an act of categorization is biased? In this chapter, it is contended that in the absence of objective norms of what categories actually are, biases in categorization can only be specified in relation to theoretical understandings of categorization. Therefore, the

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

    Science.gov (United States)

    Wohlin, Åsa

    2015-03-21

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

  15. Approximate Bias Correction in Econometrics

    OpenAIRE

    James G. MacKinnon; Anthony A. Smith Jr.

    1995-01-01

    This paper discusses ways to reduce the bias of consistent estimators that are biased in finite samples. It is necessary that the bias function, which relates parameter values to bias, should be estimable by computer simulation or by some other method. If so, bias can be reduced or, in some cases that may not be unrealistic, even eliminated. In general, several evaluations of the bias function will be required to do this. Unfortunately, reducing bias may increase the variance, or even the mea...

  16. Bias in phylogenetic reconstruction of vertebrate rhodopsin sequences.

    Science.gov (United States)

    Chang, B S; Campbell, D L

    2000-08-01

    Two spurious nodes were found in phylogenetic analyses of vertebrate rhodopsin sequences in comparison with well-established vertebrate relationships. These spurious reconstructions were well supported in bootstrap analyses and occurred independently of the method of phylogenetic analysis used (parsimony, distance, or likelihood). Use of this data set of vertebrate rhodopsin sequences allowed us to exploit established vertebrate relationships, as well as the considerable amount known about the molecular evolution of this gene, in order to identify important factors contributing to the spurious reconstructions. Simulation studies using parametric bootstrapping indicate that it is unlikely that the spurious nodes in the parsimony analyses are due to long branches or other topological effects. Rather, they appear to be due to base compositional bias at third positions, codon bias, and convergent evolution at nucleotide positions encoding the hydrophobic residues isoleucine, leucine, and valine. LogDet distance methods, as well as maximum-likelihood methods which allow for nonstationary changes in base composition, reduce but do not entirely eliminate support for the spurious resolutions. Inclusion of five additional rhodopsin sequences in the phylogenetic analyses largely corrected one of the spurious reconstructions while leaving the other unaffected. The additional sequences not only were more proximal to the corrected node, but were also found to have intermediate levels of base composition and codon bias as compared with neighboring sequences on the tree. This study shows that the spurious reconstructions can be corrected either by excluding third positions, as well as those encoding the amino acids Ile, Val, and Leu (which may not be ideal, as these sites can contain useful phylogenetic signal for other parts of the tree), or by the addition of sequences that reduce problems associated with convergent evolution.

  17. Greek Physical Education Teachers' Gender Biases in Learning and Teaching

    Science.gov (United States)

    Mouratidou, Katerina; Barkoukis, Vassilis

    2018-01-01

    Gender biases have often been observed in physical education (PE) classes, as many teachers adopt a male-biased perspective in teaching and learning. This might affect their evaluation of students' behavior and may lead students to accept and reproduce gender biases in other social contexts. The aim of this study was to examine whether PE teachers…

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pavel V Baranov

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

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sylvia Michelina Fernandes Brenna

    2004-01-01

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

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

    Science.gov (United States)

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

    1981-01-01

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

  4. Skill-Biased Technological Change in Denmark

    DEFF Research Database (Denmark)

    Malchow-Møller, Nikolaj; Rose Skaksen, Jan

    2003-01-01

    Skill-Biased Technological Change in Denmark:A Disaggregate Perspective@*In this paper, we provide an industry-level analysis of skill-biased technological change(SBTC) in Denmark over the last two decades. The analysis shows that SBTC has variedconsiderably across industries, and traditionally...... large Danish industries have experiencedrelatively less SBTC. This may partly explain why wage inequality between skilled and lessskilled has risen less in Denmark than in other countries. We also find that SBTC has beenconcentrated in already skill-intensive industries. This contains important...... information aboutfuture labour requirements, as the relative importance of these industries must be expectedto grow, thereby reinforcing the shift in demand for skilled labour.JEL Classification: J24, J31, L6Keywords: skill-biased technological change, Danish industries...

  5. Cognitive biases can affect moral intuitions about cognitive enhancement

    Directory of Open Access Journals (Sweden)

    Lucius eCaviola

    2014-10-01

    Full Text Available Research into cognitive biases that impair human judgment has mostly been applied to the area of economic decision-making. Ethical decision-making has been comparatively neglected. Since ethical decisions often involve very high individual as well as collective stakes, analyzing how cognitive biases affect them can be expected to yield important results. In this theoretical article, we consider the ethical debate about cognitive enhancement (CE and suggest a number of cognitive biases that are likely to affect moral intuitions and judgments about CE: status quo bias, loss aversion, risk aversion, omission bias, scope insensitivity, nature bias, and optimistic bias. We find that there are more well-documented biases that are likely to cause irrational aversion to CE than biases in the opposite direction. This suggests that common attitudes about CE are predominantly negatively biased. Within this new perspective, we hope that subsequent research will be able to elaborate this hypothesis and develop effective de-biasing techniques that can help increase the rationality of the public CE debate and thus improve our ethical decision-making.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Science.gov (United States)

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

    2009-06-26

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

  8. Bias aware Kalman filters

    DEFF Research Database (Denmark)

    Drecourt, J.-P.; Madsen, H.; Rosbjerg, Dan

    2006-01-01

    This paper reviews two different approaches that have been proposed to tackle the problems of model bias with the Kalman filter: the use of a colored noise model and the implementation of a separate bias filter. Both filters are implemented with and without feedback of the bias into the model state....... The colored noise filter formulation is extended to correct both time correlated and uncorrelated model error components. A more stable version of the separate filter without feedback is presented. The filters are implemented in an ensemble framework using Latin hypercube sampling. The techniques...... are illustrated on a simple one-dimensional groundwater problem. The results show that the presented filters outperform the standard Kalman filter and that the implementations with bias feedback work in more general conditions than the implementations without feedback. 2005 Elsevier Ltd. All rights reserved....

  9. Biases in casino betting

    Directory of Open Access Journals (Sweden)

    James Sundali

    2006-07-01

    Full Text Available We examine two departures of individual perceptions of randomness from probability theory: the hot hand and the gambler's fallacy, and their respective opposites. This paper's first contribution is to use data from the field (individuals playing roulette in a casino to demonstrate the existence and impact of these biases that have been previously documented in the lab. Decisions in the field are consistent with biased beliefs, although we observe significant individual heterogeneity in the population. A second contribution is to separately identify these biases within a given individual, then to examine their within-person correlation. We find a positive and significant correlation across individuals between hot hand and gambler's fallacy biases, suggesting a common (root cause of the two related errors. We speculate as to the source of this correlation (locus of control, and suggest future research which could test this speculation.

  10. Introduction to Unconscious Bias

    Science.gov (United States)

    Schmelz, Joan T.

    2010-05-01

    We all have biases, and we are (for the most part) unaware of them. In general, men and women BOTH unconsciously devalue the contributions of women. This can have a detrimental effect on grant proposals, job applications, and performance reviews. Sociology is way ahead of astronomy in these studies. When evaluating identical application packages, male and female University psychology professors preferred 2:1 to hire "Brian” over "Karen” as an assistant professor. When evaluating a more experienced record (at the point of promotion to tenure), reservations were expressed four times more often when the name was female. This unconscious bias has a repeated negative effect on Karen's career. This talk will introduce the concept of unconscious bias and also give recommendations on how to address it using an example for a faculty search committee. The process of eliminating unconscious bias begins with awareness, then moves to policy and practice, and ends with accountability.

  11. Australia's Bond Home Bias

    OpenAIRE

    Anil V. Mishra; Umaru B. Conteh

    2014-01-01

    This paper constructs the float adjusted measure of home bias and explores the determinants of bond home bias by employing the International Monetary Fund's high quality dataset (2001 to 2009) on cross-border bond investment. The paper finds that Australian investors' prefer investing in countries with higher economic development and more developed bond markets. Exchange rate volatility appears to be an impediment for cross-border bond investment. Investors prefer investing in countries with ...

  12. The unique genomic properties of sex-biased genes: Insights from avian microarray data

    Directory of Open Access Journals (Sweden)

    Webster Matthew T

    2008-03-01

    Full Text Available Abstract Background In order to develop a framework for the analysis of sex-biased genes, we present a characterization of microarray data comparing male and female gene expression in 18 day chicken embryos for brain, gonad, and heart tissue. Results From the 15982 significantly expressed coding regions that have been assigned to either the autosomes or the Z chromosome (12979 in brain, 13301 in gonad, and 12372 in heart, roughly 18% were significantly sex-biased in any one tissue, though only 4 gene targets were biased in all tissues. The gonad was the most sex-biased tissue, followed by the brain. Sex-biased autosomal genes tended to be expressed at lower levels and in fewer tissues than unbiased gene targets, and autosomal somatic sex-biased genes had more expression noise than similar unbiased genes. Sex-biased genes linked to the Z-chromosome showed reduced expression in females, but not in males, when compared to unbiased Z-linked genes, and sex-biased Z-linked genes were also expressed in fewer tissues than unbiased Z coding regions. Third position GC content, and codon usage bias showed some sex-biased effects, primarily for autosomal genes expressed in the gonad. Finally, there were several over-represented Gene Ontology terms in the sex-biased gene sets. Conclusion On the whole, this analysis suggests that sex-biased genes have unique genomic and organismal properties that delineate them from genes that are expressed equally in males and females.

  13. Simulating publication bias

    DEFF Research Database (Denmark)

    Paldam, Martin

    is censoring: selection by the size of estimate; SR3 selects the optimal combination of fit and size; and SR4 selects the first satisficing result. The last four SRs are steered by priors and result in bias. The MST and the FAT-PET have been developed for detection and correction of such bias. The simulations......Economic research typically runs J regressions for each selected for publication – it is often selected as the ‘best’ of the regressions. The paper examines five possible meanings of the word ‘best’: SR0 is ideal selection with no bias; SR1 is polishing: selection by statistical fit; SR2...... are made by data variation, while the model is the same. It appears that SR0 generates narrow funnels much at odds with observed funnels, while the other four funnels look more realistic. SR1 to SR4 give the mean a substantial bias that confirms the prior causing the bias. The FAT-PET MRA works well...

  14. Measuring Agricultural Bias

    DEFF Research Database (Denmark)

    Jensen, Henning Tarp; Robinson, Sherman; Tarp, Finn

    The measurement issue is the key issue in the literature on trade policy-induced agri-cultural price incentive bias. This paper introduces a general equilibrium effective rate of protection (GE-ERP) measure, which extends and generalizes earlier partial equilibrium nominal protection measures...... shares and intersectoral linkages - are crucial for determining the sign and magnitude of trade policy bias. The GE-ERP measure is therefore uniquely suited to capture the full impact of trade policies on agricultural price incentives. A Monte Carlo procedure confirms that the results are robust....... For the 15 sample countries, the results indicate that the agricultural price incentive bias, which was generally perceived to exist during the 1980s, was largely eliminated during the 1990s. The results also demonstrate that general equilibrium effects and country-specific characteristics - including trade...

  15. Is racial bias malleable? Whites' lay theories of racial bias predict divergent strategies for interracial interactions.

    Science.gov (United States)

    Neel, Rebecca; Shapiro, Jenessa R

    2012-07-01

    How do Whites approach interracial interactions? We argue that a previously unexamined factor-beliefs about the malleability of racial bias-guides Whites' strategies for difficult interracial interactions. We predicted and found that those who believe racial bias is malleable favor learning-oriented strategies such as taking the other person's perspective and trying to learn why an interaction is challenging, whereas those who believe racial bias is fixed favor performance-oriented strategies such as overcompensating in the interaction and trying to end the interaction as quickly as possible. Four studies support these predictions. Whether measured (Studies 1, 3, and 4) or manipulated (Study 2), beliefs that racial bias is fixed versus malleable yielded these divergent strategies for difficult interracial interactions. Furthermore, beliefs about the malleability of racial bias are distinct from related constructs (e.g., prejudice and motivations to respond without prejudice; Studies 1, 3, and 4) and influence self-reported (Studies 1-3) and actual (Study 4) strategies in imagined (Studies 1-2) and real (Studies 3-4) interracial interactions. Together, these findings demonstrate that beliefs about the malleability of racial bias influence Whites' approaches to and strategies within interracial interactions. PsycINFO Database Record (c) 2012 APA, all rights reserved

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

    Science.gov (United States)

    Wang, Pei; Song, Fan; Cai, Wanzhi

    2014-01-01

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

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

    Science.gov (United States)

    Mirzaei, Maryam; Saffar, Behnaz; Shareghi, Behzad

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Bergthorsson Ulfar

    2011-09-01

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

  19. Approach bias for food cues in obese individuals.

    Science.gov (United States)

    Kemps, Eva; Tiggemann, Marika

    2015-01-01

    This study aimed to investigate the existence of an approach bias for food cues in obese individuals. A community sample of 56 obese women and 56 normal weight controls completed an approach-avoidance variant of the implicit association task. The obese participants were faster to respond to trials that paired food words with approach words, and trials that paired non-food words with avoid words, than the converse pairings, thus, demonstrating an approach bias for food. This bias was evident for both high caloric and low caloric food words, and was not attributable to a state of deprivation or feelings of hunger. By contrast, the normal weight controls did not show any such bias. The results are consistent with recent neurocognitive perspectives of obesity. At a practical level, approach biases for food may present a potential target for modifying (excessive) food intake.

  20. Measuring agricultural policy bias

    DEFF Research Database (Denmark)

    Jensen, Henning Tarp; Robinson, Sherman; Tarp, Finn

    2010-01-01

    Measurement is a key issue in the literature on price incentive bias induced by trade policy. We introduce a general equilibrium measure of the relative effective rate of protection, which generalizes earlier protection measures. For our fifteen sample countries, results indicate that the agricul...

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

    Science.gov (United States)

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

    2013-01-11

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

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

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

    2017-12-12

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

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

    Directory of Open Access Journals (Sweden)

    Manuel Hiss

    2017-10-01

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

  6. Conceptual and methodological biases in network models.

    Science.gov (United States)

    Lamm, Ehud

    2009-10-01

    Many natural and biological phenomena can be depicted as networks. Theoretical and empirical analyses of networks have become prevalent. I discuss theoretical biases involved in the delineation of biological networks. The network perspective is shown to dissolve the distinction between regulatory architecture and regulatory state, consistent with the theoretical impossibility of distinguishing a priori between "program" and "data." The evolutionary significance of the dynamics of trans-generational and interorganism regulatory networks is explored and implications are presented for understanding the evolution of the biological categories development-heredity, plasticity-evolvability, and epigenetic-genetic.

  7. Estimation bias and bias correction in reduced rank autoregressions

    DEFF Research Database (Denmark)

    Nielsen, Heino Bohn

    2017-01-01

    This paper characterizes the finite-sample bias of the maximum likelihood estimator (MLE) in a reduced rank vector autoregression and suggests two simulation-based bias corrections. One is a simple bootstrap implementation that approximates the bias at the MLE. The other is an iterative root...

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

    Science.gov (United States)

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

    2012-01-01

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

  9. Transition-transversion bias is not universal: a counter example from grasshopper pseudogenes.

    Directory of Open Access Journals (Sweden)

    Irene Keller

    2007-02-01

    Full Text Available Comparisons of the DNA sequences of metazoa show an excess of transitional over transversional substitutions. Part of this bias is due to the relatively high rate of mutation of methylated cytosines to thymine. Postmutation processes also introduce a bias, particularly selection for codon-usage bias in coding regions. It is generally assumed, however, that there is a universal bias in favour of transitions over transversions, possibly as a result of the underlying chemistry of mutation. Surprisingly, this underlying trend has been evaluated only in two types of metazoan, namely Drosophila and the Mammalia. Here, we investigate a third group, and find no such bias. We characterize the point substitution spectrum in Podisma pedestris, a grasshopper species with a very large genome. The accumulation of mutations was surveyed in two pseudogene families, nuclear mitochondrial and ribosomal DNA sequences. The cytosine-guanine (CpG dinucleotides exhibit the high transition frequencies expected of methylated sites. The transition rate at other cytosine residues is significantly lower. After accounting for this methylation effect, there is no significant difference between transition and transversion rates. These results contrast with reports from other taxa and lead us to reject the hypothesis of a universal transition/transversion bias. Instead we suggest fundamental interspecific differences in point substitution processes.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ivaylo P. Ivanov

    2017-06-01

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

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

    Science.gov (United States)

    Parto, Sahar; Lartillot, Nicolas

    2017-06-23

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    DEFF Research Database (Denmark)

    Knudsen, Steen; Brunak, Søren

    1997-01-01

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

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

    NARCIS (Netherlands)

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

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

  18. Physicians and implicit bias: how doctors may unwittingly perpetuate health care disparities.

    Science.gov (United States)

    Chapman, Elizabeth N; Kaatz, Anna; Carnes, Molly

    2013-11-01

    Although the medical profession strives for equal treatment of all patients, disparities in health care are prevalent. Cultural stereotypes may not be consciously endorsed, but their mere existence influences how information about an individual is processed and leads to unintended biases in decision-making, so called "implicit bias". All of society is susceptible to these biases, including physicians. Research suggests that implicit bias may contribute to health care disparities by shaping physician behavior and producing differences in medical treatment along the lines of race, ethnicity, gender or other characteristics. We review the origins of implicit bias, cite research documenting the existence of implicit bias among physicians, and describe studies that demonstrate implicit bias in clinical decision-making. We then present the bias-reducing strategies of consciously taking patients' perspectives and intentionally focusing on individual patients' information apart from their social group. We conclude that the contribution of implicit bias to health care disparities could decrease if all physicians acknowledged their susceptibility to it, and deliberately practiced perspective-taking and individuation when providing patient care. We further conclude that increasing the number of African American/Black physicians could reduce the impact of implicit bias on health care disparities because they exhibit significantly less implicit race bias.

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

    DEFF Research Database (Denmark)

    Gonzalez de Valdivia, Ernesto I; Isaksson, Leif A

    2005-01-01

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

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

    Science.gov (United States)

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

    2017-12-27

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

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

    Directory of Open Access Journals (Sweden)

    Thomas H A Ederveen

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

  2. Exchange bias theory

    International Nuclear Information System (INIS)

    Kiwi, Miguel

    2001-01-01

    Research on the exchange bias (EB) phenomenon has witnessed a flurry of activity during recent years, which stems from its use in magnetic sensors and as stabilizers in magnetic reading heads. EB was discovered in 1956 but it attracted only limited attention until these applications, closely related to giant magnetoresistance, were developed during the last decade. In this review, I initially give a short introduction, listing the most salient experimental results and what is required from an EB theory. Next, I indicate some of the obstacles in the road towards a satisfactory understanding of the phenomenon. The main body of the text reviews and critically discusses the activity that has flourished, mainly during the last 5 years, in the theoretical front. Finally, an evaluation of the progress made, and a critical assessment as to where we stand nowadays along the road to a satisfactory theory, is presented

  3. Bias modification training can alter approach bias and chocolate consumption.

    Science.gov (United States)

    Schumacher, Sophie E; Kemps, Eva; Tiggemann, Marika

    2016-01-01

    Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Reconceptualizing Individual Differences in Self-Enhancement Bias: An Interpersonal Approach

    Science.gov (United States)

    Kwan, Virginia S. Y.; John, Oliver P.; Kenny, David A.; Bond, Michael H.; Robins, Richard W.

    2004-01-01

    Self-enhancement bias has been studied from 2 perspectives: L. Festinger's (1954) social comparison theory (self-enhancers perceive themselves more positively than they perceive others) and G. W. Allport's (1937) self-insight theory (self-enhancers perceive themselves more positively than they are perceived by others). These 2 perspectives are…

  5. HIV1 V3 loop hypermutability is enhanced by the guanine usage bias in the part of env gene coding for it.

    Science.gov (United States)

    Khrustalev, Vladislav Victorovich

    2009-01-01

    Guanine is the most mutable nucleotide in HIV genes because of frequently occurring G to A transitions, which are caused by cytosine deamination in viral DNA minus strands catalyzed by APOBEC enzymes. Distribution of guanine between three codon positions should influence the probability for G to A mutation to be nonsynonymous (to occur in first or second codon position). We discovered that nucleotide sequences of env genes coding for third variable regions (V3 loops) of gp120 from HIV1 and HIV2 have different kinds of guanine usage biases. In the HIV1 reference strain and 100 additionally analyzed HIV1 strains the guanine usage bias in V3 loop coding regions (2G>1G>3G) should lead to elevated nonsynonymous G to A transitions occurrence rates. In the HIV2 reference strain and 100 other HIV2 strains guanine usage bias in V3 loop coding regions (3G>2G>1G) should protect V3 loops from hypermutability. According to the HIV1 and HIV2 V3 alignment, insertion of the sequence enriched with 2G (21 codons in length) occurred during the evolution of HIV1 predecessor, while insertion of the different sequence enriched with 3G (19 codons in length) occurred during the evolution of HIV2 predecessor. The higher is the level of 3G in the V3 coding region, the lower should be the immune escaping mutation occurrence rates. This hypothesis was tested in this study by comparing the guanine usage in V3 loop coding regions from HIV1 fast and slow progressors. All calculations have been performed by our algorithms "VVK In length", "VVK Dinucleotides" and "VVK Consensus" (www.barkovsky.hotmail.ru).

  6. Concluding Remarks: Experiment from a materials perspective

    International Nuclear Information System (INIS)

    Fisk, Z

    2011-01-01

    The author provides some remarks regarding the current status of experiments in strongly correlated electron systems. By construction, they are biased by the author's perspectives at the time of writing.

  7. Religious Attitudes and Home Bias

    OpenAIRE

    C. Reggiani; G. Rossini

    2008-01-01

    Home bias affects trade in goods, services and financial assets. It is mostly generated by "natural" trade barriers. Among these dividers we may list many behavioral and sociological factors, such as status quo biases and a few kind of ‘embeddedness’. Unfortunately these factors are difficult to measure. An important part of ‘embeddedness’ may be related to religious attitudes. Is there any relation between economic home bias and religious attitudes at the individual tier? Our aim is to provi...

  8. Bias in clinical intervention research

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte

    2006-01-01

    Research on bias in clinical trials may help identify some of the reasons why investigators sometimes reach the wrong conclusions about intervention effects. Several quality components for the assessment of bias control have been suggested, but although they seem intrinsically valid, empirical...... evidence is needed to evaluate their effects on the extent and direction of bias. This narrative review summarizes the findings of methodological studies on the influence of bias in clinical trials. A number of methodological studies suggest that lack of adequate randomization in published trial reports...

  9. Information environment, behavioral biases, and home bias in analysts’ recommendations

    DEFF Research Database (Denmark)

    Farooq, Omar; Taouss, Mohammed

    2012-01-01

    Can information environment of a firm explain home bias in analysts’ recommendations? Can the extent of agency problems explain optimism difference between foreign and local analysts? This paper answers these questions by documenting the effect of information environment on home bias in analysts’...

  10. Threat bias, not negativity bias, underpins differences in political ideology.

    Science.gov (United States)

    Lilienfeld, Scott O; Latzman, Robert D

    2014-06-01

    Although disparities in political ideology are rooted partly in dispositional differences, Hibbing et al.'s analysis paints with an overly broad brush. Research on the personality correlates of liberal-conservative differences points not to global differences in negativity bias, but to differences in threat bias, probably emanating from differences in fearfulness. This distinction bears implications for etiological research and persuasion efforts.

  11. Selection of functional 2A sequences within foot-and-mouth disease virus; requirements for the NPGP motif with a distinct codon bias

    DEFF Research Database (Denmark)

    Kjær, Jonas; Belsham, Graham J.

    2018-01-01

    Foot-and-mouth disease virus (FMDV) has a positive-sense ssRNA genome including a single, large, open reading frame. Splitting of the encoded polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues long) which induces a non-proteolytic, co-translational, "cleavage" at its own C......-terminus. A conserved feature among variants of 2A is the C-terminal motif N16P17G18/P19 where P19 is the first residue of 2B. It has been shown previously that certain amino acid substitutions can be tolerated at residues E14, S15 and N16 within the 2A sequence of infectious FMDVs but no variants at residues P17, G18...... or P19 have been identified. In this study, using highly degenerate primers, we analysed if any other residues can be present at each position of the NPG/P motif within infectious FMDV. No alternative forms of this motif were found to be encoded by rescued FMDVs after 2, 3 or 4 passages. However...

  12. Evidence of codon usage in the nearest neighbor spacing distribution of bases in bacterial genomes

    Science.gov (United States)

    Higareda, M. F.; Geiger, O.; Mendoza, L.; Méndez-Sánchez, R. A.

    2012-02-01

    Statistical analysis of whole genomic sequences usually assumes a homogeneous nucleotide density throughout the genome, an assumption that has been proved incorrect for several organisms since the nucleotide density is only locally homogeneous. To avoid giving a single numerical value to this variable property, we propose the use of spectral statistics, which characterizes the density of nucleotides as a function of its position in the genome. We show that the cumulative density of bases in bacterial genomes can be separated into an average (or secular) plus a fluctuating part. Bacterial genomes can be divided into two groups according to the qualitative description of their secular part: linear and piecewise linear. These two groups of genomes show different properties when their nucleotide spacing distribution is studied. In order to analyze genomes having a variable nucleotide density, statistically, the use of unfolding is necessary, i.e., to get a separation between the secular part and the fluctuations. The unfolding allows an adequate comparison with the statistical properties of other genomes. With this methodology, four genomes were analyzed Burkholderia, Bacillus, Clostridium and Corynebacterium. Interestingly, the nearest neighbor spacing distributions or detrended distance distributions are very similar for species within the same genus but they are very different for species from different genera. This difference can be attributed to the difference in the codon usage.

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

    Science.gov (United States)

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

    2015-04-01

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

  14. Dual Systems for Spatial Updating in Immediate and Retrieved Environments: Evidence from Bias Analysis.

    Science.gov (United States)

    Liu, Chuanjun; Xiao, Chengli

    2018-01-01

    The spatial updating and memory systems are employed during updating in both the immediate and retrieved environments. However, these dual systems seem to work differently, as the difference of pointing latency and absolute error between the two systems vary across environments. To verify this issue, the present study employed the bias analysis of signed errors based on the hypothesis that the transformed representation will bias toward the original one. Participants learned a spatial layout and then either stayed in the learning location or were transferred to a neighboring room directly or after being disoriented. After that, they performed spatial judgments from perspectives aligned with the learning direction, aligned with the direction they faced during the test, or a novel direction misaligned with the two above-mentioned directions. The patterns of signed error bias were consistent across environments. Responses for memory aligned perspectives were unbiased, whereas responses for sensorimotor aligned perspectives were biased away from the memory aligned perspective, and responses for misaligned perspectives were biased toward sensorimotor aligned perspectives. These findings indicate that the spatial updating system is consistently independent of the spatial memory system regardless of the environments, but the updating system becomes less accessible as the environment changes from immediate to a retrieved one.

  15. Dual Systems for Spatial Updating in Immediate and Retrieved Environments: Evidence from Bias Analysis

    Directory of Open Access Journals (Sweden)

    Chuanjun Liu

    2018-02-01

    Full Text Available The spatial updating and memory systems are employed during updating in both the immediate and retrieved environments. However, these dual systems seem to work differently, as the difference of pointing latency and absolute error between the two systems vary across environments. To verify this issue, the present study employed the bias analysis of signed errors based on the hypothesis that the transformed representation will bias toward the original one. Participants learned a spatial layout and then either stayed in the learning location or were transferred to a neighboring room directly or after being disoriented. After that, they performed spatial judgments from perspectives aligned with the learning direction, aligned with the direction they faced during the test, or a novel direction misaligned with the two above-mentioned directions. The patterns of signed error bias were consistent across environments. Responses for memory aligned perspectives were unbiased, whereas responses for sensorimotor aligned perspectives were biased away from the memory aligned perspective, and responses for misaligned perspectives were biased toward sensorimotor aligned perspectives. These findings indicate that the spatial updating system is consistently independent of the spatial memory system regardless of the environments, but the updating system becomes less accessible as the environment changes from immediate to a retrieved one.

  16. Heuristic Biases in Mathematical Reasoning

    Science.gov (United States)

    Inglis, Matthew; Simpson, Adrian

    2005-01-01

    In this paper we briefly describe the dual process account of reasoning, and explain the role of heuristic biases in human thought. Concentrating on the so-called matching bias effect, we describe a piece of research that indicates a correlation between success at advanced level mathematics and an ability to override innate and misleading…

  17. Gender bias affects forests worldwide

    Science.gov (United States)

    Marlène Elias; Susan S Hummel; Bimbika S Basnett; Carol J.P. Colfer

    2017-01-01

    Gender biases persist in forestry research and practice. These biases result in reduced scientific rigor and inequitable, ineffective, and less efficient policies, programs, and interventions. Drawing from a two-volume collection of current and classic analyses on gender in forests, we outline five persistent and inter-related themes: gendered governance, tree tenure,...

  18. Anti-Bias Education: Reflections

    Science.gov (United States)

    Derman-Sparks, Louise

    2011-01-01

    It is 30 years since NAEYC published "Anti-Bias Curriculum Tools for Empowering Young Children" (Derman-Sparks & ABC Task Force, 1989). Since then, anti-bias education concepts have become part of the early childhood education (ECE) narrative in the United States and many other countries. It has brought a fresh way of thinking about…

  19. Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion protein at codon 180

    International Nuclear Information System (INIS)

    Ishida, S.; Sugino, M.; Shinoda, K.; Ohsawa, N.; Koizumi, N.; Ohta, T.; Kitamoto, T.; Tateishi, J.

    1995-01-01

    We report a 66-year-old woman with histologically diagnosed Creutzfeld-Jacob disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated expansion of the high cortical signal on T2-weighted images, which differs from previous MRI reports of CJD. This patient followed an atypical clinical course: 16 months had passed before she developed akinetic mutism, and periodic sharp waves had not been detected on EEG after 2 years in spite of her akinetic mutism. Brain biopsy showed primary spongiform changes in the grey matter, and a point mutation of the prion protein gene at codon 180 was discovered using polymerase chain reaction direct sequencing and Tth 111 I cutting. This is the first case with the point mutation of the codon 180 variant with an atypical clinical course and characteristic MRI findings. (orig.)

  20. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A

    2002-01-01

    on parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin......, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels......AIMS: The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism...

  1. Understanding the tropical warm temperature bias simulated by climate models

    Science.gov (United States)

    Brient, Florent; Schneider, Tapio

    2017-04-01

    The state-of-the-art coupled general circulation models have difficulties in representing the observed spatial pattern of surface tempertaure. A majority of them suffers a warm bias in the tropical subsiding regions located over the eastern parts of oceans. These regions are usually covered by low-level clouds scattered from stratus along the coasts to more vertically developed shallow cumulus farther from them. Models usually fail to represent accurately this transition. Here we investigate physical drivers of this warm bias in CMIP5 models through a near-surface energy budget perspective. We show that overestimated solar insolation due to a lack of stratocumulus mostly explains the warm bias. This bias also arises partly from inter-model differences in surface fluxes that could be traced to differences in near-surface relative humidity and air-sea temperature gradient. We investigate the role of the atmosphere in driving surface biases by comparing historical and atmopsheric (AMIP) experiments. We show that some differences in boundary-layer characteristics, mostly those related to cloud fraction and relative humidity, are already present in AMIP experiments and may be the drivers of coupled biases. This gives insights in how models can be improved for better simulations of the tropical climate.

  2. Epistemological and ethical assessment of obesity bias in industrialized countries

    Directory of Open Access Journals (Sweden)

    Azétsop Jacquineau

    2011-12-01

    Full Text Available Abstract Bernard Lonergan's cognitive theory challenges us to raise questions about both the cognitive process through which obesity is perceived as a behaviour change issue and the objectivity of such a moral judgment. Lonergan's theory provides the theoretical tools to affirm that anti-fat discrimination, in the United States of America and in many industrialized countries, is the result of both a group bias that resists insights into the good of other groups and a general bias of anti-intellectualism that tends to set common sense against insights that require any thorough scientific analyses. While general bias diverts the public's attention away from the true aetiology of obesity, group bias sustains an anti-fat culture that subtly legitimates discriminatory practices and policies against obese people. Although anti-discrimination laws may seem to be a reasonable way of protecting obese and overweight individuals from discrimination, obesity bias can be best addressed by reframing the obesity debate from an environmental perspective from which tools and strategies to address both the social and individual determinants of obesity can be developed. Attention should not be concentrated on individuals' behaviour as it is related to lifestyle choices, without giving due consideration to the all-encompassing constraining factors which challenge the social and rational blindness of obesity bias.

  3. A System for Anesthesia Drug Administration Using Barcode Technology: The Codonics Safe Label System and Smart Anesthesia Manager.

    Science.gov (United States)

    Jelacic, Srdjan; Bowdle, Andrew; Nair, Bala G; Kusulos, Dolly; Bower, Lynnette; Togashi, Kei

    2015-08-01

    Many anesthetic drug errors result from vial or syringe swaps. Scanning the barcodes on vials before drug preparation, creating syringe labels that include barcodes, and scanning the syringe label barcodes before drug administration may help to prevent errors. In contrast, making syringe labels by hand that comply with the recommendations of regulatory agencies and standards-setting bodies is tedious and time consuming. A computerized system that uses vial barcodes and generates barcoded syringe labels could address both safety issues and labeling recommendations. We measured compliance of syringe labels in multiple operating rooms (ORs) with the recommendations of regulatory agencies and standards-setting bodies before and after the introduction of the Codonics Safe Label System (SLS). The Codonics SLS was then combined with Smart Anesthesia Manager software to create an anesthesia barcode drug administration system, which allowed us to measure the rate of scanning syringe label barcodes at the time of drug administration in 2 cardiothoracic ORs before and after introducing a coffee card incentive. Twelve attending cardiothoracic anesthesiologists and the OR satellite pharmacy participated. The use of the Codonics SLS drug labeling system resulted in >75% compliant syringe labels (95% confidence interval, 75%-98%). All syringe labels made using the Codonics SLS system were compliant. The average rate of scanning barcodes on syringe labels using Smart Anesthesia Manager was 25% (730 of 2976) over 13 weeks but increased to 58% (956 of 1645) over 8 weeks after introduction of a simple (coffee card) incentive (P < 0.001). An anesthesia barcode drug administration system resulted in a moderate rate of scanning syringe label barcodes at the time of drug administration. Further, adaptation of the system will be required to achieve a higher utilization rate.

  4. Large-scale galaxy bias

    Science.gov (United States)

    Desjacques, Vincent; Jeong, Donghui; Schmidt, Fabian

    2018-02-01

    This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy statistics. We then review the excursion-set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  5. Large-scale galaxy bias

    Science.gov (United States)

    Jeong, Donghui; Desjacques, Vincent; Schmidt, Fabian

    2018-01-01

    Here, we briefly introduce the key results of the recent review (arXiv:1611.09787), whose abstract is as following. This review presents a comprehensive overview of galaxy bias, that is, the statistical relation between the distribution of galaxies and matter. We focus on large scales where cosmic density fields are quasi-linear. On these scales, the clustering of galaxies can be described by a perturbative bias expansion, and the complicated physics of galaxy formation is absorbed by a finite set of coefficients of the expansion, called bias parameters. The review begins with a detailed derivation of this very important result, which forms the basis of the rigorous perturbative description of galaxy clustering, under the assumptions of General Relativity and Gaussian, adiabatic initial conditions. Key components of the bias expansion are all leading local gravitational observables, which include the matter density but also tidal fields and their time derivatives. We hence expand the definition of local bias to encompass all these contributions. This derivation is followed by a presentation of the peak-background split in its general form, which elucidates the physical meaning of the bias parameters, and a detailed description of the connection between bias parameters and galaxy (or halo) statistics. We then review the excursion set formalism and peak theory which provide predictions for the values of the bias parameters. In the remainder of the review, we consider the generalizations of galaxy bias required in the presence of various types of cosmological physics that go beyond pressureless matter with adiabatic, Gaussian initial conditions: primordial non-Gaussianity, massive neutrinos, baryon-CDM isocurvature perturbations, dark energy, and modified gravity. Finally, we discuss how the description of galaxy bias in the galaxies' rest frame is related to clustering statistics measured from the observed angular positions and redshifts in actual galaxy catalogs.

  6. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice.

    Science.gov (United States)

    Wanner, Roger M; Güthlein, Carolin; Springer, Burkhard; Böttger, Erik C; Ackermann, Martin

    2008-05-28

    The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  7. Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice

    Directory of Open Access Journals (Sweden)

    Ackermann Martin

    2008-05-01

    Full Text Available Abstract Background The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. Results We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. Conclusion These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

  8. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634).

    Science.gov (United States)

    Jesić, Maja D; Tancić-Gajić, Milina; Jesić, Milos M; Zivaljević, Vladan; Sajić, Silvija; Vujović, Svetlana; Damjanović, Svetozar

    2014-01-01

    The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. This is a case report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  9. Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.

    Science.gov (United States)

    Lavania, Mallika; Hena, Abu; Reja, Hasanoor; Nigam, Astha; Biswas, Nibir Kumar; Singh, Itu; Turankar, Ravindra P; Gupta, Ud; Kumar, Senthil; Rewaria, Latika; Patra, Pradip K R; Sengupta, Utpal; Bhattacharya, Basudeb

    2016-03-01

    Rifampicin is the major drug in the treatment of leprosy. The rifampicin resistance of Mycobacterium leprae results from a mutation in the rpoB gene, encoding the β subunit of RNA polymerase. As M. leprae is a non-cultivable organism observation of its growth using mouse food-pad (MFP) is the only Gold Standard assay used for confirmation of "in-vivo" drug resistance. Any mutation at molecular level has to be verified by MFP assay for final confirmation of drug resistance in leprosy. In the present study, M. leprae strains showing a mutation only at codon 442 Gln-His and along with mutation either at codon 424 Val-Gly or at 438 Gln-Val within the Rifampicin Resistance Determining Region (RRDR) confirmed by DNA sequencing and by high resolution melting (HRM) analysis were subjected for its growth in MFP. The M. leprae strain having the new mutation at codon 442 Gln-His was found to be sensitive to all the three drugs and strains having additional mutations at 424 Val-Gly and 438 Gln-Val were conferring resistance with Multi drug therapy (MDT) in MFP. These results indicate that MFP is the gold standard method for confirming the mutations detected by molecular techniques.

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

    Directory of Open Access Journals (Sweden)

    Suneeth F Mathew

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

  11. Functional role of bacteriophage transfer RNAs: codon usage analysis of genomic sequences stored in the GENBANK/EMBL/DDBJ databases

    Directory of Open Access Journals (Sweden)

    T Kunisawa

    2006-01-01

    Full Text Available Complete genomic sequence data are stored in the public GenBank/EMBL/DDBJ databases so that any investigator can make use of the data. This report describes a comparative analysis of codon usage that is impossible without such a public and open data system. A limited number of bacteriophages harbor their own transfer RNAs. Based on a comparison between T4 phage-encoded tRNA species and the relative cellular amounts of host Escherichia coli tRNAs, it is hypothesized that T4 tRNAs could serve to supplement host isoacceptor tRNA species that are present in minor amounts and thus enhance the translational efficiency of phage proteins. When compared to their respective host bacteria, the codon usage data of bacteriophages D3, φC31, HP1, D29 and 933W all show an increased frequency of synonymous codons or amino acids that correspond to phage tRNA species, suggesting their supplemental role in the efficient production of phage proteins. The data-analysis presents an example in which the availability of an open and fully accessible database system would allow one to obtain comprehensive insights into a fundamental problem in molecular biology.

  12. Cognitive Bias in Systems Verification

    Science.gov (United States)

    Larson, Steve

    2012-01-01

    Working definition of cognitive bias: Patterns by which information is sought and interpreted that can lead to systematic errors in decisions. Cognitive bias is used in diverse fields: Economics, Politics, Intelligence, Marketing, to name a few. Attempts to ground cognitive science in physical characteristics of the cognitive apparatus exceed our knowledge. Studies based on correlations; strict cause and effect is difficult to pinpoint. Effects cited in the paper and discussed here have been replicated many times over, and appear sound. Many biases have been described, but it is still unclear whether they are all distinct. There may only be a handful of fundamental biases, which manifest in various ways. Bias can effect system verification in many ways . Overconfidence -> Questionable decisions to deploy. Availability -> Inability to conceive critical tests. Representativeness -> Overinterpretation of results. Positive Test Strategies -> Confirmation bias. Debiasing at individual level very difficult. The potential effect of bias on the verification process can be managed, but not eliminated. Worth considering at key points in the process.

  13. Administrative bias in South Africa

    Directory of Open Access Journals (Sweden)

    E S Nwauche

    2005-01-01

    Full Text Available This article reviews the interpretation of section 6(2(aii of the Promotion of Administrative Justice Act which makes an administrator “biased or reasonably suspected of bias” a ground of judicial review. In this regard, the paper reviews the determination of administrative bias in South Africa especially highlighting the concept of institutional bias. The paper notes that inspite of the formulation of the bias ground of review the test for administrative bias is the reasonable apprehension test laid down in the case of President of South Africa v South African Rugby Football Union(2 which on close examination is not the same thing. Accordingly the paper urges an alternative interpretation that is based on the reasonable suspicion test enunciated in BTR Industries South Africa (Pty Ltd v Metal and Allied Workers Union and R v Roberts. Within this context, the paper constructs a model for interpreting the bias ground of review that combines the reasonable suspicion test as interpreted in BTR Industries and R v Roberts, the possibility of the waiver of administrative bias, the curative mechanism of administrative appeal as well as some level of judicial review exemplified by the jurisprudence of article 6(1 of the European Convention of Human Rights, especially in the light of the contemplation of the South African Magistrate Court as a jurisdictional route of judicial review.

  14. Strategi Mengatasi Common Measures Bias dalam Balanced Scorecard

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    Sekar Akrom Faradiza

    2016-06-01

    Balanced Scorecard (BSC is a comprehensive performance measurement. BSC is not only used financial indicators but also non financial indicators there are customer, internal process business and learning and growth perspective. By using BSC, evaluators have common and unique measures. When evaluate manager performance, evaluator tends to only use common measures and ignore unique measures. This is called common measures bias. This study aims to investigate whether dissaggregated and aggregated BSC and management communication can overcome common measures bias and intent to BSC approach. This study also will evaluate whether these approach will affect evaluator decision when allocated compensation. We conduct 2x2x2 experiment of undergraduate accounting students. Participant act as a senior manager and evaluate the performance of two divisions and then allocated the bonus. ANOVA repeated measurement are used to conduct hypothesis test. The results showed that dissaggregated BSC and management communication could not overcome common measures bias but effected  management decision when allocated compensation.

  15. Start codon targeted (scot polymorphism reveals genetic diversity in european old maize (zea mays l. Genotypes

    Directory of Open Access Journals (Sweden)

    Martin Vivodík

    2016-11-01

    Full Text Available Maize (Zea mays L. is one of the world's most important crop plants following wheat and rice, which provides staple food to large number of human population in the world. It is cultivated in a wider range of environments than wheat and rice because of its greater adaptability. Molecular characterization is frequently used by maize breeders as an alternative method for selecting more promising genotypes and reducing the cost and time needed to develop hybrid combinations. In the present investigation 40 genotypes of maize from Czechoslovakia, Hungary, Poland, Union of Soviet Socialist Republics, Slovakia and Yugoslavia were analysed using 20 Start codon targeted (SCoT markers. These primers produced total 114 fragments across 40 maize genotypes, of which 86 (76.43% were polymorphic with an average of 4.30 polymorphic fragments per primer and number of amplified fragments ranged from 2 (SCoT 45 to 8 (SCoT 28 and SCoT 63. The polymorphic information content (PIC value ranged from 0.374 (ScoT 45 to 0.846 (SCoT 28 with an average of 0.739. The dendrogram based on hierarchical cluster analysis using UPGMA algorithm was prepared. The hierarchical cluster analysis showed that the maize genotypes were divided into two main clusters. Unique maize genotype (cluster 1, Zuta Brzica, originating from Yugoslavia separated from others. Cluster 2 was divided into two main clusters (2a and 2b. Subcluster 2a contained one Yugoslavian genotype Juhoslavanska and subcluster 2b was divided in two subclusters 2ba and 2bb. The present study shows effectiveness of employing SCoT markers in analysis of maize, and would be useful for further studies in population genetics, conservation genetics and genotypes improvement.

  16. TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2007-11-01

    Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

  17. Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes*

    Science.gov (United States)

    Takeuchi, Atsuko; Kobayashi, Atsushi; Ironside, James W.; Mohri, Shirou; Kitamoto, Tetsuyuki

    2013-01-01

    To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein (PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in individuals with a PRNP codon 129 genotype other than M/M and transmission studies using animal models have raised the concern that all humans might be susceptible to vCJD prions, especially via secondary infection. To reevaluate this possibility and to analyze in detail the transmission properties of vCJD prions to transgenic animals carrying distinct codon 129 genotype, we performed intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in mouse lines were susceptible to vCJD infection, although the attack rate gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP deposition including florid/amyloid plaques in the brain also gradually decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of protease-resistant abnormal PrP in the brain and transmissibility of these humanized mouse-passaged vCJD prions upon subpassage into knock-in mice expressing bovine PrP were not affected by the codon 129 genotype. These results indicate that individuals with the 129V/V genotype may be more susceptible to secondary vCJD infection than expected and may lack the neuropathological characteristics observed in vCJD patients with the 129M/M genotype. Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype. PMID:23792955

  18. Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes.

    Science.gov (United States)

    Takeuchi, Atsuko; Kobayashi, Atsushi; Ironside, James W; Mohri, Shirou; Kitamoto, Tetsuyuki

    2013-07-26

    To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein (PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in individuals with a PRNP codon 129 genotype other than M/M and transmission studies using animal models have raised the concern that all humans might be susceptible to vCJD prions, especially via secondary infection. To reevaluate this possibility and to analyze in detail the transmission properties of vCJD prions to transgenic animals carrying distinct codon 129 genotype, we performed intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in mouse lines were susceptible to vCJD infection, although the attack rate gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP deposition including florid/amyloid plaques in the brain also gradually decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of protease-resistant abnormal PrP in the brain and transmissibility of these humanized mouse-passaged vCJD prions upon subpassage into knock-in mice expressing bovine PrP were not affected by the codon 129 genotype. These results indicate that individuals with the 129V/V genotype may be more susceptible to secondary vCJD infection than expected and may lack the neuropathological characteristics observed in vCJD patients with the 129M/M genotype. Besides the molecular typing of protease-resistant PrP in the brain, transmission studies using knock-in mice carrying bovine PrP may aid the differential diagnosis of secondary vCJD infection, especially in individuals with the 129V/V genotype.

  19. Identification and codon reading properties of 5-cyanomethyl uridine, a new modified nucleoside found in the anticodon wobble position of mutant haloarchaeal isoleucine tRNAs.

    Science.gov (United States)

    Mandal, Debabrata; Köhrer, Caroline; Su, Dan; Babu, I Ramesh; Chan, Clement T Y; Liu, Yuchen; Söll, Dieter; Blum, Paul; Kuwahara, Masayasu; Dedon, Peter C; Rajbhandary, Uttam L

    2014-02-01

    Most archaea and bacteria use a modified C in the anticodon wobble position of isoleucine tRNA to base pair with A but not with G of the mRNA. This allows the tRNA to read the isoleucine codon AUA without also reading the methionine codon AUG. To understand why a modified C, and not U or modified U, is used to base pair with A, we mutated the C34 in the anticodon of Haloarcula marismortui isoleucine tRNA (tRNA2(Ile)) to U, expressed the mutant tRNA in Haloferax volcanii, and purified and analyzed the tRNA. Ribosome binding experiments show that although the wild-type tRNA2(Ile) binds exclusively to the isoleucine codon AUA, the mutant tRNA binds not only to AUA but also to AUU, another isoleucine codon, and to AUG, a methionine codon. The G34 to U mutant in the anticodon of another H. marismortui isoleucine tRNA species showed similar codon binding properties. Binding of the mutant tRNA to AUG could lead to misreading of the AUG codon and insertion of isoleucine in place of methionine. This result would explain why most archaea and bacteria do not normally use U or a modified U in the anticodon wobble position of isoleucine tRNA for reading the codon AUA. Biochemical and mass spectrometric analyses of the mutant tRNAs have led to the discovery of a new modified nucleoside, 5-cyanomethyl U in the anticodon wobble position of the mutant tRNAs. 5-Cyanomethyl U is present in total tRNAs from euryarchaea but not in crenarchaea, eubacteria, or eukaryotes.

  20. Critical Thinking and Cognitive Bias

    Directory of Open Access Journals (Sweden)

    Jeffrey Maynes

    2015-05-01

    Full Text Available Teaching critical thinking skill is a central pedagogical aim in many courses. These skills, it is hoped, will be both portable (applicable in a wide range of contexts and durable (not forgotten quickly. Yet, both of these virtues are challenged by pervasive and potent cognitive biases, such as motivated reasoning, false consensus bias and hindsight bias. In this paper, I argue that a focus on the development of metacognitive skill shows promise as a means to inculcate debiasing habits in students. Such habits will help students become more critical reasoners. I close with suggestions for implementing this strategy.

  1. Association between the p53 codon 72 polymorphism and primary open-angle glaucoma risk: Meta-analysis based on 11 case–control studies

    Directory of Open Access Journals (Sweden)

    Mohsen Gohari

    2016-01-01

    Full Text Available The TP53 is important in functions of cell cycle control, apoptosis, and maintenance of DNA integrity. Studies on the association between p53 codon 72 polymorphism and primary open-angle glaucoma (POAG risk have yielded conflicting results. Published literature from PubMed and Web of Science databases was retrieved. All studies evaluating the association between p53 codon 72 polymorphisms and POAG were included. Pooled odds ratio (OR and 95% confidence interval (CI were calculated. Eleven separate studies including 2541 cases and 1844 controls were pooled in the meta-analysis. We did not detect a significant association between POAG risk and p53 codon 72 polymorphism overall population except allele genetic model (C vs. G: OR = 0.961, 95% CI = 0.961–0.820, P = 0.622. In the stratified analysis for Asians and Caucasians, there was an association between p53 codon 72 polymorphism and POAG. In the dominant model in the overall population and by ethnicity subgroups, the highest elevated POAG risk was presented. In summary, these results indicate that p53 codon 72 polymorphism is likely an important genetic factor contributing to susceptibility of POAG. However, more case–controls studies based on larger sample size and stratified by ethnicity are suggested to further clarify the relationship between p53 codon 72 polymorphism and POAG.

  2. Preferences, country bias, and international trade

    NARCIS (Netherlands)

    S. Roy (Santanu); J.M.A. Viaene (Jean-Marie)

    1998-01-01

    textabstractAnalyzes international trade where consumer preferences exhibit country bias. Why country biases arise; How trade can occur in the presence of country bias; Implication for the pattern of trade and specialization.

  3. Benzimidazole -Resistance in Haemonchus Contortus: New PCR-RFLP Method for the Detection of Point Mutation at Codon 167 of Isotype 1 Β-Tubulin Gene

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    A Eslami

    2012-12-01

    Full Text Available Background: Due to the lack of a suitable and economic test for the analysis of the polymorphism at codon 167, we developed a new PCR-RFLP technique, based on a modified forward primer (UT-HC167 MF-primer, to identify simultaneously the SNPs at codons 167 and 200 of isotype 1 β-tubu­lin gene of Haemonchus contortus.Methods: There already are several safe and easy methods for identification of point mutations at codons 198 and 200. Due to the lack of a reliable and easy method for the detection of the single nucleo­tide polymorphism (SNP at codon 167, we developed an innovative PCR-RFLP technique based on a modified forward primer (UT-HC167 MF-primer, in which the nucleotide T at the posi­tion 443 was substituted through a nucleotide A creating a restriction site for restriction endonuc­lease SnaB I in the nucleotide sequences including codon 167. A total of 138 adult male H. contortus were collected from three different geo-climatic areas of Iran. The isolated genomic DNA of each single worm was amplified by PCR using primers flanking codon 167. The PCR product (527 bp was then amplified by semi-nested PCR using the UT-HC167 MF-primer and the reverse primer achiev­ing a PCR product of 451 bp in length. This PCR product was subsequently digested with the restriction endonucleases SnaB I and TaaI for analysis of the mutations at codons 167 and 200, respec­tively.Results: All worms had two alleles encoding for phenylalanine (BZss homozygote for both codons.Conclusion: Using the UT-HC167 MF-primer and a suitable reverse primer designed upstream from codon 200, it is possible to amplify a PCR product which can be used for analysis of the SNPs at all three mentioned codons using RFLP.

  4. Association between p53 codon 72 polymorphism and systemic lupus erythematosus

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    Mohammad Nabavi

    2014-06-01

    Full Text Available Aim : Systemic lupus erythematosus (SLE is a systemic vasculitic disorder, with multiple genes involved in the disease pathogenesis. The p53 gene plays an important role in controlling the cell cycle. We aimed to study the prevalence of p53 polymorphism in SLE patients and analyze the relationship between the p53 polymorphism and clinical-laboratory features of the disease. Material and methods : This case-control study was conducted on patients with confirmed SLE at Namazi Hospital, Shiraz, Iran. Seventy-seven patients with SLE including 9 (11.8% men and 68 (88.2% women with mean age of 25.61 ±10.69 years and 80 healthy controls with mean age of 51.82 ±14.25 years were included. The patients’ information, including the epidemiological profile, disease history, disease symptoms and also the laboratory findings, were extracted from the hospital records. The p53 expression was determined in lyzed lymphocytes. The data were analyzed using SPSS software version 14.00 for Windows considering p < 0.05 as statistically significant. Results : The frequencies of Arg/Arg, Pro/Pro and Arg/Pro among normal controls were 38.8%, 28.8% and 37.5%, respectively, but in the patients, Arg/Arg, Pro/Pro and Arg/Pro genotypes frequencies were shown to be 29.2%, 12.3% and 58.5%, respectively. Thus, heterozygous form of this polymorphism was shown to be associated with the disease more than the homozygous alleles. There was a significant relationship between the different allele types of p53 and some clinical features of SLE. There was no association between the different allele types and any of the initial manifestations of the disease and the laboratory findings, as well. Conclusions: In an Iranian population the functional oncoprotein of p53 with codon 72 polymorphism may play an important role in the pathogenesis and clinical presentation of SLE.

  5. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K.C.; Qiu, Jian-Wen

    2017-01-01

    responses of two congeneric snails to various hypoxic conditions, as well as codon substitution analysis at transcriptomic level to detect signals of positive selection in hypoxia-responsive genes. The integrated physiological, proteomic and transcriptomic approach can be applied in other non-model species to understand the molecular mechanisms of adaptation to global environmental change.

  6. Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

    KAUST Repository

    Mu, Huawei

    2017-11-06

    responses of two congeneric snails to various hypoxic conditions, as well as codon substitution analysis at transcriptomic level to detect signals of positive selection in hypoxia-responsive genes. The integrated physiological, proteomic and transcriptomic approach can be applied in other non-model species to understand the molecular mechanisms of adaptation to global environmental change.

  7. Speed Biases With Real-Life Video Clips

    Directory of Open Access Journals (Sweden)

    Federica Rossi

    2018-03-01

    Full Text Available We live almost literally immersed in an artificial visual world, especially motion pictures. In this exploratory study, we asked whether the best speed for reproducing a video is its original, shooting speed. By using adjustment and double staircase methods, we examined speed biases in viewing real-life video clips in three experiments, and assessed their robustness by manipulating visual and auditory factors. With the tested stimuli (short clips of human motion, mixed human-physical motion, physical motion and ego-motion, speed underestimation was the rule rather than the exception, although it depended largely on clip content, ranging on average from 2% (ego-motion to 32% (physical motion. Manipulating display size or adding arbitrary soundtracks did not modify these speed biases. Estimated speed was not correlated with estimated duration of these same video clips. These results indicate that the sense of speed for real-life video clips can be systematically biased, independently of the impression of elapsed time. Measuring subjective visual tempo may integrate traditional methods that assess time perception: speed biases may be exploited to develop a simple, objective test of reality flow, to be used for example in clinical and developmental contexts. From the perspective of video media, measuring speed biases may help to optimize video reproduction speed and validate “natural” video compression techniques based on sub-threshold temporal squeezing.

  8. CEO emotional bias and investment decision, Bayesian network method

    Directory of Open Access Journals (Sweden)

    Jarboui Anis

    2012-08-01

    Full Text Available This research examines the determinants of firms’ investment introducing a behavioral perspective that has received little attention in corporate finance literature. The following central hypothesis emerges from a set of recently developed theories: Investment decisions are influenced not only by their fundamentals but also depend on some other factors. One factor is the biasness of any CEO to their investment, biasness depends on the cognition and emotions, because some leaders use them as heuristic for the investment decision instead of fundamentals. This paper shows how CEO emotional bias (optimism, loss aversion and overconfidence affects the investment decisions. The proposed model of this paper uses Bayesian Network Method to examine this relationship. Emotional bias has been measured by means of a questionnaire comprising several items. As for the selected sample, it has been composed of some 100 Tunisian executives. Our results have revealed that the behavioral analysis of investment decision implies leader affected by behavioral biases (optimism, loss aversion, and overconfidence adjusts its investment choices based on their ability to assess alternatives (optimism and overconfidence and risk perception (loss aversion to create of shareholder value and ensure its place at the head of the management team.

  9. Negativity Bias in Dangerous Drivers.

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    Jing Chai

    Full Text Available The behavioral and cognitive characteristics of dangerous drivers differ significantly from those of safe drivers. However, differences in emotional information processing have seldom been investigated. Previous studies have revealed that drivers with higher anger/anxiety trait scores are more likely to be involved in crashes and that individuals with higher anger traits exhibit stronger negativity biases when processing emotions compared with control groups. However, researchers have not explored the relationship between emotional information processing and driving behavior. In this study, we examined the emotional information processing differences between dangerous drivers and safe drivers. Thirty-eight non-professional drivers were divided into two groups according to the penalty points that they had accrued for traffic violations: 15 drivers with 6 or more points were included in the dangerous driver group, and 23 drivers with 3 or fewer points were included in the safe driver group. The emotional Stroop task was used to measure negativity biases, and both behavioral and electroencephalograph data were recorded. The behavioral results revealed stronger negativity biases in the dangerous drivers than in the safe drivers. The bias score was correlated with self-reported dangerous driving behavior. Drivers with strong negativity biases reported having been involved in mores crashes compared with the less-biased drivers. The event-related potentials (ERPs revealed that the dangerous drivers exhibited reduced P3 components when responding to negative stimuli, suggesting decreased inhibitory control of information that is task-irrelevant but emotionally salient. The influence of negativity bias provides one possible explanation of the effects of individual differences on dangerous driving behavior and traffic crashes.

  10. Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sigal, R.J.; Doria, A.; Warram, J.H.; Krolewski, A.S. [Joslin Diabetes Center, Boston, MA (United States)

    1996-04-01

    Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-AGG single base substitution (corresponding to a glycine-arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG{r_arrow}AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases ({approximately}3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight. 9 refs., 2 tabs.

  11. Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

    Science.gov (United States)

    Larocca, Nancy; Moreno, Dolores; Garmendia, Jenny Valentina; Velasquez, Olga; Martin-Rojo, Joana; Talamo, Carlos; Garcia, Alexis; De Sanctis, Juan Bautista

    2013-12-01

    One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.

  12. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634

    Directory of Open Access Journals (Sweden)

    Ješić Maja D.

    2014-01-01

    Full Text Available Introduction. The multiple endocrine neoplasia type 2A (MEN 2A syndrome, comprising medullary thyroid carcinoma (MTC, pheochromocytoma and primary hyperparathyroidism (PHPT is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy’s father and grandmother and paternal aunt in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml, has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  13. SCREENING FOR GENETIC CHANGES AND CODON 129 POLYMORPHISM IN PRNP GENE IN HEALTHY SLOVENIAN POPULATION AND SPORADIC CASES OF CREUTZFELDT-JAKOB DISEASE

    Directory of Open Access Journals (Sweden)

    Sava Smerkolj

    2004-11-01

    Full Text Available Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD. Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes.Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer.Results. Methionine homozygotes comprised 46.8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%, 1 was valine homozygote (8.3% and 1 was heterozygote (8.3%.Found SNPs were combination of codon 76 change (228C > T and codon 84 change (252T > C in a single sample of healthy population, combination of codon 68 change (204T > C and codon 76 change (228C > T in two samples of healthy population and codon 117 change (351A > G in a healthy population sample and in a valine homozygote patient.Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD, because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non-familial, sporadic disease form.

  14. Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

    Science.gov (United States)

    Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A

    2018-02-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

  15. Numerical value biases sound localization.

    Science.gov (United States)

    Golob, Edward J; Lewald, Jörg; Getzmann, Stephan; Mock, Jeffrey R

    2017-12-08

    Speech recognition starts with representations of basic acoustic perceptual features and ends by categorizing the sound based on long-term memory for word meaning. However, little is known about whether the reverse pattern of lexical influences on basic perception can occur. We tested for a lexical influence on auditory spatial perception by having subjects make spatial judgments of number stimuli. Four experiments used pointing or left/right 2-alternative forced choice tasks to examine perceptual judgments of sound location as a function of digit magnitude (1-9). The main finding was that for stimuli presented near the median plane there was a linear left-to-right bias for localizing smaller-to-larger numbers. At lateral locations there was a central-eccentric location bias in the pointing task, and either a bias restricted to the smaller numbers (left side) or no significant number bias (right side). Prior number location also biased subsequent number judgments towards the opposite side. Findings support a lexical influence on auditory spatial perception, with a linear mapping near midline and more complex relations at lateral locations. Results may reflect coding of dedicated spatial channels, with two representing lateral positions in each hemispace, and the midline area represented by either their overlap or a separate third channel.

  16. Polyglutamine repeats are associated to specific sequence biases that are conserved among eukaryotes.

    Directory of Open Access Journals (Sweden)

    Matteo Ramazzotti

    Full Text Available Nine human neurodegenerative diseases, including Huntington's disease and several spinocerebellar ataxia, are associated to the aggregation of proteins comprising an extended tract of consecutive glutamine residues (polyQs once it exceeds a certain length threshold. This event is believed to be the consequence of the expansion of polyCAG codons during the replication process. This is in apparent contradiction with the fact that many polyQs-containing proteins remain soluble and are encoded by invariant genes in a number of eukaryotes. The latter suggests that polyQs expansion and/or aggregation might be counter-selected through a genetic and/or protein context. To identify this context, we designed a software that scrutinize entire proteomes in search for imperfect polyQs. The nature of residues flanking the polyQs and that of residues other than Gln within polyQs (insertions were assessed. We discovered strong amino acid residue biases robustly associated to polyQs in the 15 eukaryotic proteomes we examined, with an over-representation of Pro, Leu and His and an under-representation of Asp, Cys and Gly amino acid residues. These biases are conserved amongst unrelated proteins and are independent of specific functional classes. Our findings suggest that specific residues have been co-selected with polyQs during evolution. We discuss the possible selective pressures responsible of the observed biases.

  17. News Consumption and Media Bias

    OpenAIRE

    Yi Xiang; Miklos Sarvary

    2007-01-01

    Bias in the market for news is well-documented. Recent research in economics explains the phenomenon by assuming that consumers want to read (watch) news that is consistent with their tastes or prior beliefs rather than the truth. The present paper builds on this idea but recognizes that (i) besides “biased” consumers, there are also “conscientious” consumers whose sole interest is in discovering the truth, and (ii) consistent with reality, media bias is constrained by the truth. These two fa...

  18. Biased limiter experiments on text

    International Nuclear Information System (INIS)

    Phillips, P.E.; Wootton, A.J.; Rowan, W.L.; Ritz, C.P.; Rhodes, T.L.; Bengtson, R.D.; Hodge, W.L.; Durst, R.D.; McCool, S.C.; Richards, B.; Gentle, K.W.; Schoch, P.; Forster, J.C.; Hickok, R.L.; Evans, T.E.

    1987-01-01

    Experiments using an electrically biased limiter have been performed on the Texas Experimental Tokamak (TEXT). A small movable limiter is inserted past the main poloidal ring limiter (which is electrically connected to the vacuum vessel) and biased at V Lim with respect to it. The floating potential, plasma potential and shear layer position can be controlled. With vertical strokeV Lim vertical stroke ≥ 50 V the plasma density increases. For V Lim Lim > 0 the results obtained are inconclusive. Variation of V Lim changes the electrostatic turbulence which may explain the observed total flux changes. (orig.)

  19. The coalitional value theory of antigay bias

    NARCIS (Netherlands)

    Winegard, Bo; Reynolds, Tania; Baumeister, Roy F.; Plant, E. Ashby

    2016-01-01

    Research indicates that antigay bias follows a specific pattern (and probably has throughout written history, at least in the West): (a) men evince more antigay bias than women; (b) men who belong to traditionally male coalitions evince more antigay bias than those who do not; (c) antigay bias is

  20. Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

    Science.gov (United States)

    Rivu, Sanzana Fareen; Apu, Mohd Nazmul Hasan; Shabnaz, Samia; Nahid, Noor Ahmed; Islam, Md Reazul; Al-Mamun, Mir Md Abdullah; Nahar, Zabun; Rabbi, Sikder Nahidul Islam; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul

    2017-08-01

    Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160Ccolorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, pcolorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (pcolorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, pcolorectal cancer development in Bangladeshi population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Codon Optimization Significantly Improves the Expression Level of α-Amylase Gene from Bacillus licheniformis in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Jian-Rong Wang

    2015-01-01

    Full Text Available α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis, the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use.

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Transgenic rice expressing a codon-modified synthetic CP4-EPSPS confers tolerance to broad-spectrum herbicide, glyphosate.

    Science.gov (United States)

    Chhapekar, Sushil; Raghavendrarao, Sanagala; Pavan, Gadamchetty; Ramakrishna, Chopperla; Singh, Vivek Kumar; Phanindra, Mullapudi Lakshmi Venkata; Dhandapani, Gurusamy; Sreevathsa, Rohini; Ananda Kumar, Polumetla

    2015-05-01

    Highly tolerant herbicide-resistant transgenic rice was developed by expressing codon-modified synthetic CP4--EPSPS. The transformants could tolerate up to 1% commercial glyphosate and has the potential to be used for DSR (direct-seeded rice). Weed infestation is one of the major biotic stress factors that is responsible for yield loss in direct-seeded rice (DSR). Herbicide-resistant rice has potential to improve the efficiency of weed management under DSR. Hence, the popular indica rice cultivar IR64, was genetically modified using Agrobacterium-mediated transformation with a codon-optimized CP4-EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, with N-terminal chloroplast targeting peptide from Petunia hybrida. Integration of the transgenes in the selected rice plants was confirmed by Southern hybridization and expression by Northern and herbicide tolerance assays. Transgenic plants showed EPSPS enzyme activity even at high concentrations of glyphosate, compared to untransformed control plants. T0, T1 and T2 lines were tested by herbicide bioassay and it was confirmed that the transgenic rice could tolerate up to 1% of commercial Roundup, which is five times more in dose used to kill weeds under field condition. All together, the transgenic rice plants developed in the present study could be used efficiently to overcome weed menace.

  4. A L2HGDH initiator methionine codon mutation in a Yorkshire terrier with L-2-hydroxyglutaric aciduria

    Directory of Open Access Journals (Sweden)

    Farias Fabiana HG

    2012-07-01

    Full Text Available Abstract Background L-2-hydroxyglutaric aciduria is a metabolic repair deficiency characterized by elevated levels of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid. Neurological signs associated with the disease in humans and dogs include seizures, ataxia and dementia. Case presentation Here we describe an 8 month old Yorkshire terrier that presented with episodes of hyperactivity and aggressive behavior. Between episodes, the dog’s behavior and neurologic examinations were normal. A T2 weighted MRI of the brain showed diffuse grey matter hyperintensity and a urine metabolite screen showed elevated 2-hydroxyglutaric acid. We sequenced all 10 exons and intron-exon borders of L2HGDH from the affected dog and identified a homozygous A to G transition in the initiator methionine codon. The first inframe methionine is at p.M183 which is past the mitochondrial targeting domain of the protein. Initiation of translation at p.M183 would encode an N-terminal truncated protein unlikely to be functional. Conclusions We have identified a mutation in the initiation codon of L2HGDH that is likely to result in a non-functional gene. The Yorkshire terrier could serve as an animal model to understand the pathogenesis of L-2-hydroxyglutaric aciduria and to evaluate potential therapies.

  5. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

    Science.gov (United States)

    BANERJI, JULIAN

    2015-01-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

  6. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

    Science.gov (United States)

    Banerji, Julian

    2015-09-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

  7. Compositional Bias in Naïve and Chemically-modified Phage-Displayed Libraries uncovered by Paired-end Deep Sequencing.

    Science.gov (United States)

    He, Bifang; Tjhung, Katrina F; Bennett, Nicholas J; Chou, Ying; Rau, Andrea; Huang, Jian; Derda, Ratmir

    2018-01-19

    Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a "naïve" library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

  8. Biased Brownian dynamics for rate constant calculation.

    OpenAIRE

    Zou, G; Skeel, R D; Subramaniam, S

    2000-01-01

    An enhanced sampling method-biased Brownian dynamics-is developed for the calculation of diffusion-limited biomolecular association reaction rates with high energy or entropy barriers. Biased Brownian dynamics introduces a biasing force in addition to the electrostatic force between the reactants, and it associates a probability weight with each trajectory. A simulation loses weight when movement is along the biasing force and gains weight when movement is against the biasing force. The sampl...

  9. Age differences in optimism bias are mediated by reliance on intuition and religiosity.

    Science.gov (United States)

    Klaczynski, Paul A

    2017-11-01

    The relationships among age, optimism bias, religiosity, creationist beliefs, and reliance on intuition were examined in a sample of 211 high school students (M age =16.54years). Optimism bias was defined as the difference between predictions for positive and negative live events (e.g., divorce) for the self and age peers. Results indicated that older adolescents displayed less optimism bias, were less religious, believed less in creationism, and relied on intuition less than younger adolescents. Furthermore, the association between age and optimism bias was mediated by religiosity and reliance on intuition but not by creationist beliefs. These findings are considered from a dual-process theoretic perspective that emphasizes age increases in metacognitive abilities and epistemological beliefs and age declines in impulsive judgments. Research directed toward examining alternative explanations of the association among religiosity, age, and optimism bias is recommended. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Exploring Attribution Theory and Bias

    Science.gov (United States)

    Robinson, Jessica A.

    2017-01-01

    Courses: This activity can be used in a wide range of classes, including interpersonal communication, introduction to communication, and small group communication. Objectives: After completing this activity, students should be able to: (1) define attribution theory, personality attribution, situational attribution, and attribution bias; (2)…

  11. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2016-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...

  12. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  13. Minimum Bias Trigger in ATLAS

    International Nuclear Information System (INIS)

    Kwee, Regina

    2010-01-01

    Since the restart of the LHC in November 2009, ATLAS has collected inelastic pp collisions to perform first measurements on charged particle densities. These measurements will help to constrain various models describing phenomenologically soft parton interactions. Understanding the trigger efficiencies for different event types are therefore crucial to minimize any possible bias in the event selection. ATLAS uses two main minimum bias triggers, featuring complementary detector components and trigger levels. While a hardware based first trigger level situated in the forward regions with 2.2 < |η| < 3.8 has been proven to select pp-collisions very efficiently, the Inner Detector based minimum bias trigger uses a random seed on filled bunches and central tracking detectors for the event selection. Both triggers were essential for the analysis of kinematic spectra of charged particles. Their performance and trigger efficiency measurements as well as studies on possible bias sources will be presented. We also highlight the advantage of these triggers for particle correlation analyses. (author)

  14. Gender bias in teaching evaluations

    NARCIS (Netherlands)

    Mengel, Friederike; Sauermann, Jan; Zölitz, Ulf Zoelitz

    2017-01-01

    This paper provides new evidence on gender bias in teaching evaluations. We exploit a quasi-experimental dataset of 19,952 student evaluations of university faculty in a context where students are randomly allocated to female or male instructors. Despite the fact that neither students’ grades nor

  15. Attentional Bias in Math Anxiety

    Directory of Open Access Journals (Sweden)

    Orly eRubinsten

    2015-10-01

    Full Text Available Cognitive theory from the field of general anxiety suggests that the tendency to display attentional bias toward negative information results in anxiety. Accordingly, the current study aims to investigate whether attentional bias is involved in math anxiety as well (i.e., a persistent negative reaction to math. Twenty seven participants (14 with high levels of math anxiety and 13 with low levels of math anxiety were presented with a novel computerized numerical version of the well established dot probe task. One of 6 types of prime stimuli, either math related or typically neutral, were presented on one side of a computer screen. The prime was preceded by a probe (either one or two asterisks that appeared in either the prime or the opposite location. Participants had to discriminate probe identity (one or two asterisks. Math anxious individuals reacted faster when the probe was at the location of the numerical related stimuli. This suggests the existence of attentional bias in math anxiety. That is, for math anxious individuals, the cognitive system selectively favored the processing of emotionally negative information (i.e., math related words. These findings suggest that attentional bias is linked to unduly intense math anxiety symptoms.

  16. Attentional bias in math anxiety.

    Science.gov (United States)

    Rubinsten, Orly; Eidlin, Hili; Wohl, Hadas; Akibli, Orly

    2015-01-01

    Cognitive theory from the field of general anxiety suggests that the tendency to display attentional bias toward negative information results in anxiety. Accordingly, the current study aims to investigate whether attentional bias is involved in math anxiety (MA) as well (i.e., a persistent negative reaction to math). Twenty seven participants (14 with high levels of MA and 13 with low levels of MA) were presented with a novel computerized numerical version of the well established dot probe task. One of six types of prime stimuli, either math related or typically neutral, was presented on one side of a computer screen. The prime was preceded by a probe (either one or two asterisks) that appeared in either the prime or the opposite location. Participants had to discriminate probe identity (one or two asterisks). Math anxious individuals reacted faster when the probe was at the location of the numerical related stimuli. This suggests the existence of attentional bias in MA. That is, for math anxious individuals, the cognitive system selectively favored the processing of emotionally negative information (i.e., math related words). These findings suggest that attentional bias is linked to unduly intense MA symptoms.

  17. Perception bias in route choice

    NARCIS (Netherlands)

    Vreeswijk, Jacob Dirk; Thomas, Tom; van Berkum, Eric C.; van Arem, Bart

    2014-01-01

    Travel time is probably one of the most studied attributes in route choice. Recently, perception of travel time received more attention as several studies have shown its importance in explaining route choice behavior. In particular, travel time estimates by travelers appear to be biased against

  18. Over Expression of a tRNALeu Isoacceptor Changes Charging Pattern of Leucine tRNAs and Reveals New Codon Reading

    DEFF Research Database (Denmark)

    Sørensen, Michael Askvad; Elf, J.; Bouakaz, E.

    2005-01-01

    During mRNA translation, synonymous codons for one amino acid are often read by different isoaccepting tRNAs. The theory of selective tRNA charging predicts greatly varying percentages of aminoacylation among isoacceptors in cells starved for their common amino acid. It also predicts major changes...... in tRNA charging patterns upon concentration changes of single isoacceptors, which suggests a novel type of translational control of gene expression. We therefore tested the theory by measuring with Northern blots the charging of Leu-tRNAs in Escherichia coli under Leu limitation in response to over...... postulated a previously unknown common codon for tRNALeu GAG and tRNALeu UAG. Subsequently, we demonstrated that the tRNALeu GAG codon CUU is, in fact, read also by tRNALeu UAG, due to a uridine-5-oxyacetic acid modification....

  19. The MSPDBL2 codon 591 polymorphism is associated with lumefantrine in vitro drug responses in Plasmodium falciparum isolates from Kilifi, Kenya.

    Science.gov (United States)

    Ochola-Oyier, Lynette Isabella; Okombo, John; Mwai, Leah; Kiara, Steven M; Pole, Lewa; Tetteh, Kevin K A; Nzila, Alexis; Marsh, Kevin

    2015-03-01

    The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used in combination with artemisinin, are still unclear. We assessed the polymorphisms of Pfmspdbl2 for associations with LUM activity in a Kenyan population. MSPDBL2 codon 591S was associated with reduced susceptibility to LUM (P = 0.04). The high frequency of Pfmspdbl2 codon 591S in Kenya may be driven by the widespread use of lumefantrine in artemisinin combination therapy (Coartem). Copyright © 2015, Ochola-Oyier et al.

  20. Contribution of single amino acid and codon substitutions to the production and secretion of a lipase by Bacillus subtilis.

    Science.gov (United States)

    Skoczinski, Pia; Volkenborn, Kristina; Fulton, Alexander; Bhadauriya, Anuseema; Nutschel, Christina; Gohlke, Holger; Knapp, Andreas; Jaeger, Karl-Erich

    2017-09-25

    Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B. subtilis model protein lipase A (LipA). We have covered the full natural diversity of single amino acid substitutions at 155 positions of LipA by site saturation mutagenesis excluding only highly conserved residues and qualitatively and quantitatively screened about 30,000 clones for extracellular LipA production. Identified variants with beneficial effects on production were sequenced and analyzed regarding B. subtilis growth behavior, extracellular lipase activity and amount as well as changes in lipase transcript levels. In total, 26 LipA variants were identified showing an up to twofold increase in either amount or activity of extracellular lipase. These variants harbor single amino acid or codon substitutions that did not substantially affect B. subtilis growth. Subsequent exemplary combination of beneficial single amino acid substitutions revealed an additive effect solely at the level of extracellular lipase amount; however, lipase amount and activity could not be increased simultaneously. Single amino acid and codon substitutions can affect LipA secretion and production by B. subtilis. Several codon-related effects were observed that either enhance lipA transcription or promote a more efficient folding of LipA. Single amino acid substitutions could improve LipA production by increasing its secretion or stability in the culture supernatant. Our findings indicate that optimization of the expression system is not sufficient for efficient protein production in B. subtilis. The sequence of the target protein should also be considered as an

  1. Variable-bias coin tossing

    International Nuclear Information System (INIS)

    Colbeck, Roger; Kent, Adrian

    2006-01-01

    Alice is a charismatic quantum cryptographer who believes her parties are unmissable; Bob is a (relatively) glamorous string theorist who believes he is an indispensable guest. To prevent possibly traumatic collisions of self-perception and reality, their social code requires that decisions about invitation or acceptance be made via a cryptographically secure variable-bias coin toss (VBCT). This generates a shared random bit by the toss of a coin whose bias is secretly chosen, within a stipulated range, by one of the parties; the other party learns only the random bit. Thus one party can secretly influence the outcome, while both can save face by blaming any negative decisions on bad luck. We describe here some cryptographic VBCT protocols whose security is guaranteed by quantum theory and the impossibility of superluminal signaling, setting our results in the context of a general discussion of secure two-party computation. We also briefly discuss other cryptographic applications of VBCT

  2. Probability biases as Bayesian inference

    Directory of Open Access Journals (Sweden)

    Andre; C. R. Martins

    2006-11-01

    Full Text Available In this article, I will show how several observed biases in human probabilistic reasoning can be partially explained as good heuristics for making inferences in an environment where probabilities have uncertainties associated to them. Previous results show that the weight functions and the observed violations of coalescing and stochastic dominance can be understood from a Bayesian point of view. We will review those results and see that Bayesian methods should also be used as part of the explanation behind other known biases. That means that, although the observed errors are still errors under the be understood as adaptations to the solution of real life problems. Heuristics that allow fast evaluations and mimic a Bayesian inference would be an evolutionary advantage, since they would give us an efficient way of making decisions. %XX In that sense, it should be no surprise that humans reason with % probability as it has been observed.

  3. Variable-bias coin tossing

    Science.gov (United States)

    Colbeck, Roger; Kent, Adrian

    2006-03-01

    Alice is a charismatic quantum cryptographer who believes her parties are unmissable; Bob is a (relatively) glamorous string theorist who believes he is an indispensable guest. To prevent possibly traumatic collisions of self-perception and reality, their social code requires that decisions about invitation or acceptance be made via a cryptographically secure variable-bias coin toss (VBCT). This generates a shared random bit by the toss of a coin whose bias is secretly chosen, within a stipulated range, by one of the parties; the other party learns only the random bit. Thus one party can secretly influence the outcome, while both can save face by blaming any negative decisions on bad luck. We describe here some cryptographic VBCT protocols whose security is guaranteed by quantum theory and the impossibility of superluminal signaling, setting our results in the context of a general discussion of secure two-party computation. We also briefly discuss other cryptographic applications of VBCT.

  4. Girl child and gender bias.

    Science.gov (United States)

    Chowdhry, D P

    1995-01-01

    This article identifies gender bias against female children and youth in India. Gender bias is based on centuries-old religious beliefs and sayings from ancient times. Discrimination is reflected in denial or ignorance of female children's educational, health, nutrition, and recreational needs. Female infanticide and selective abortion of female fetuses are other forms of discrimination. The task of eliminating or reducing gender bias will involve legal, developmental, political, and administrative measures. Public awareness needs to be created. There is a need to reorient the education and health systems and to advocate for gender equality. The government of India set the following goals for the 1990s: to protect the survival of the girl child and practice safe motherhood; to develop the girl child in general; and to protect vulnerable girl children in different circumstances and in special groups. The Health Authorities should monitor the laws carefully to assure marriage after the minimum age, ban sex determination of the fetus, and monitor the health and nutrition of pre-school girls and nursing and pregnant mothers. Mothers need to be encouraged to breast feed, and to breast feed equally between genders. Every village and slum area needs a mini health center. Maternal mortality must decline. Primary health centers and hospitals need more women's wards. Education must be universally accessible. Enrollments should be increased by educating rural tribal and slum parents, reducing distances between home and school, making curriculum more relevant to girls, creating more female teachers, and providing facilities and incentives for meeting the needs of girl students. Supplementary income could be provided to families for sending girls to school. Recreational activities must be free of gender bias. Dowry, sati, and devdasi systems should be banned.

  5. Competition and Commercial Media Bias

    OpenAIRE

    Blasco, Andrea; Sobbrio, Francesco

    2011-01-01

    This paper reviews the empirical evidence on commercial media bias (i.e., advertisers influence over media accuracy) and then introduces a simple model to summarize the main elements of the theoretical literature. The analysis provides three main policy insights for media regulators: i) Media regulators should target their monitoring efforts towards news contents upon which advertisers are likely to share similar preferences; ii) In advertising industries characterized by high correlation in ...

  6. BEHAVIORAL BIASES IN TRADING SECURITIES

    Directory of Open Access Journals (Sweden)

    Turcan Ciprian Sebastian

    2010-12-01

    Full Text Available The main thesis of this paper represents the importance and the effects that human behavior has over capital markets. It is important to see the link between the asset valuation and investor sentiment that motivate to pay for an asset a certain prices over/below the intrinsic value. The main behavioral aspects discussed are emotional factors such as: fear of regret, overconfidence, perseverance, loss aversion ,heuristic biases, misinformation and thinking errors, herding and their consequences.

  7. Significant biases affecting abundance determinations

    Science.gov (United States)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  8. Galaxy formation and physical bias

    Science.gov (United States)

    Cen, Renyue; Ostriker, Jeremiah P.

    1992-01-01

    We have supplemented our code, which computes the evolution of the physical state of a representative piece of the universe to include, not only the dynamics of dark matter (with a standard PM code), and the hydrodynamics of the gaseous component (including detailed collisional and radiative processes), but also galaxy formation on a heuristic but plausible basis. If, within a cell the gas is Jeans' unstable, collapsing, and cooling rapidly, it is transformed to galaxy subunits, which are then followed with a collisionless code. After grouping them into galaxies, we estimate the relative distributions of galaxies and dark matter and the relative velocities of galaxies and dark matter. In a large scale CDM run of 80/h Mpc size with 8 x 10 exp 6 cells and dark matter particles, we find that physical bias b is on the 8/h Mpc scale is about 1.6 and increases towards smaller scales, and that velocity bias is about 0.8 on the same scale. The comparable HDM simulation is highly biased with b = 2.7 on the 8/h Mpc scale. Implications of these results are discussed in the light of the COBE observations which provide an accurate normalization for the initial power spectrum. CDM can be ruled out on the basis of too large a predicted small scale velocity dispersion at greater than 95 percent confidence level.

  9. Opinion dynamics with confirmation bias.

    Directory of Open Access Journals (Sweden)

    Armen E Allahverdyan

    Full Text Available Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science.We formulate a (non-Bayesian model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect-when consecutively exposed to two opinions, the preference is given to the last opinion (recency or the first opinion (primacy -and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties.The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development.

  10. The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, S.J.; Gladwin, A.J.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1997-03-01

    Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mutations, which are spread throughout the gene, are presented. This brings the total reported to date to 35, which represents a detection rate of 60%. Of the mutations that have been reported to date, all but one result in the introduction of a premature-termination codon into the predicted protein, treacle. Moreover, the mutations are largely family specific, although a common 5-bp deletion in exon 24 (seven different families) and a recurrent splicing mutation in intron 3 (two different families) have been identified. This mutational spectrum supports the hypothesis that TCS results from haploin-sufficiency. 49 refs., 4 figs., 3 tabs.

  11. Matrilateral Bias in Human Grandmothering

    Directory of Open Access Journals (Sweden)

    Martin Daly

    2017-09-01

    Full Text Available Children receive more care and resources from their maternal grandmothers than from their paternal grandmothers. This asymmetry is the “matrilateral bias” in grandmaternal investment. Here, we synopsize the evolutionary theories that predict such a bias, and review evidence of its cross-cultural generality and magnitude. Evolutionists have long maintained that investing in a daughter’s child yields greater fitness returns, on average, than investing in a son’s child because of paternity uncertainty: the son’s putative progeny may have been sired by someone else. Recent theoretical work has identified an additional natural selective basis for the matrilateral bias that may be no less important: supporting grandchildren lightens the load on their mother, increasing her capacity to pursue her fitness in other ways, and if she invests those gains either in her natal relatives or in children of a former or future partner, fitness returns accrue to the maternal, but not the paternal, grandmother. In modern democracies, where kinship is reckoned bilaterally and no postmarital residence norms restrict grandmaternal access to grandchildren, many studies have found large matrilateral biases in contact, childcare, and emotional closeness. In other societies, patrilineal ideology and postmarital residence with the husband’s kin (virilocality might be expected to have produced a patrilateral bias instead, but the available evidence refutes this hypothesis. In hunter-gatherers, regardless of professed norms concerning kinship and residence, mothers get needed help at and after childbirth from their mothers, not their mothers-in-law. In traditional agricultural and pastoral societies, patrilineal and virilocal norms are common, but young mothers still turn to their natal families for crucial help, and several studies have documented benefits, including reduced child mortality, associated with access to maternal, but not paternal, grandmothers. Even

  12. Why can't we just get along? Interpersonal biases and interracial distrust

    NARCIS (Netherlands)

    Dovidio, J.F.; Gaertner, S.L.; Kawakami, K.L.; Hodson, G.

    2002-01-01

    The authors review a series of studies that illustrate how one form of contemporary racial bias of Whites, aversive racism, can shape different perspectives of Blacks and Whites in ways that can undermine race relations. This research demonstrates that contemporary racism among Whites is subtle,

  13. Examining the influence of psychopathy, hostility biases, and automatic processing on criminal offenders' Theory of Mind

    NARCIS (Netherlands)

    Nentjes, L.; Bernstein, D.; Arntz, A.; van Breukelen, G.; Slaats, M.

    2015-01-01

    Theory of Mind (ToM) is a social perceptual skill that refers to the ability to take someone else's perspective and infer what others think. The current study examined the effect of potential hostility biases, as well as controlled (slow) versus automatic (fast) processing on ToM performance in

  14. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  15. Bias-correction in vector autoregressive models

    DEFF Research Database (Denmark)

    Engsted, Tom; Pedersen, Thomas Quistgaard

    2014-01-01

    We analyze the properties of various methods for bias-correcting parameter estimates in both stationary and non-stationary vector autoregressive models. First, we show that two analytical bias formulas from the existing literature are in fact identical. Next, based on a detailed simulation study......, we show that when the model is stationary this simple bias formula compares very favorably to bootstrap bias-correction, both in terms of bias and mean squared error. In non-stationary models, the analytical bias formula performs noticeably worse than bootstrapping. Both methods yield a notable...... improvement over ordinary least squares. We pay special attention to the risk of pushing an otherwise stationary model into the non-stationary region of the parameter space when correcting for bias. Finally, we consider a recently proposed reduced-bias weighted least squares estimator, and we find...

  16. The Probability Distribution for a Biased Spinner

    Science.gov (United States)

    Foster, Colin

    2012-01-01

    This article advocates biased spinners as an engaging context for statistics students. Calculating the probability of a biased spinner landing on a particular side makes valuable connections between probability and other areas of mathematics. (Contains 2 figures and 1 table.)

  17. Short Communication: Gender Bias and Stigmatization against ...

    African Journals Online (AJOL)

    Short Communication: Gender Bias and Stigmatization against Women Living with ... In Ethiopia, HIV/AIDS is highly stigmatized due to the fact that sexual ... bias, socio-economic situations and traditional beliefs contribute, individually and in ...

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  19. Is there bias in editorial choice? Yes

    OpenAIRE

    Moustafa, Khaled

    2018-01-01

    Nature has recently published a Correspondence claiming the absence of fame biases in the editorial choice. The topic is interesting and deserves a deeper analysis than it was presented because the reported brief analysis and its conclusion are somewhat biased for many reasons, some of them are discussed here. Since the editorial assessment is a form of peer-review, the biases reported on external peer-reviews would, thus, apply to the editorial assessment, too. The biases would be proportion...

  20. Bias-field equalizer for bubble memories

    Science.gov (United States)

    Keefe, G. E.

    1977-01-01

    Magnetoresistive Perm-alloy sensor monitors bias field required to maintain bubble memory. Sensor provides error signal that, in turn, corrects magnitude of bias field. Error signal from sensor can be used to control magnitude of bias field in either auxiliary set of bias-field coils around permanent magnet field, or current in small coils used to remagnetize permanent magnet by infrequent, short, high-current pulse or short sequence of pulses.

  1. mRNA secondary structure at start AUG codon is a key limiting factor for human protein expression in Escherichia coli

    International Nuclear Information System (INIS)

    Zhang Weici; Xiao Weihua; Wei Haiming; Zhang Jian; Tian Zhigang

    2006-01-01

    Codon usage and thermodynamic optimization of the 5'-end of mRNA have been applied to improve the efficiency of human protein production in Escherichia coli. However, high level expression of human protein in E. coli is still a challenge that virtually depends upon each individual target genes. Using human interleukin 10 (huIL-10) and interferon α (huIFN-α) coding sequences, we systematically analyzed the influence of several major factors on expression of human protein in E. coli. The results from huIL-10 and reinforced by huIFN-α showed that exposing AUG initiator codon from base-paired structure within mRNA itself significantly improved the translation of target protein, which resulted in a 10-fold higher protein expression than the wild-type genes. It was also noted that translation process was not affected by the retained short-range stem-loop structure at Shine-Dalgarno (SD) sequences. On the other hand, codon-optimized constructs of huIL-10 showed unimproved levels of protein expression, on the contrary, led to a remarkable RNA degradation. Our study demonstrates that exposure of AUG initiator codon from long-range intra-strand secondary structure at 5'-end of mRNA may be used as a general strategy for human protein production in E. coli

  2. The Accuracy Enhancing Effect of Biasing Cues

    NARCIS (Netherlands)

    W. Vanhouche (Wouter); S.M.J. van Osselaer (Stijn)

    2009-01-01

    textabstractExtrinsic cues such as price and irrelevant attributes have been shown to bias consumers’ product judgments. Results in this article replicate those findings in pretrial judgments but show that such biasing cues can improve quality judgments at a later point in time. Initially biasing

  3. Biased managers, organizational design, and incentive provision

    OpenAIRE

    Moreira, Humberto Ataíde; Costa, Cristiano Machado; Ferreira, Daniel Bernardo Soares

    2004-01-01

    Rio de Janeiro We model the tradeoff between the balance and the strength of incentives implicit in the choice between hierarchical and matrix organizational structures. We show that managerial biases determine which structure is optimal: hierarchical forms are preferred when biases are low, while matrix structures are preferred when biases are high.

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

    Science.gov (United States)

    Schuster, W; Brennicke, A

    1991-01-01

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

  5. Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon.

    Science.gov (United States)

    Feeney, Morgan A; Chandra, Govind; Findlay, Kim C; Paget, Mark S B; Buttner, Mark J

    2017-06-13

    The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry. IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR - rsrA , we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance

  6. Evaluating Judicial Performance and Addressing Gender Bias

    Directory of Open Access Journals (Sweden)

    Angela Melville

    2014-12-01

    Full Text Available Elek and Rottman argue that judicial evaluation is often biased against women and minority judges. The need to address bias is important, however often the desire for diversity seems so self-evident as to belie deeper analysis. This paper examines the two main rationales for gender equality on the bench. First, female judges are often considered necessary in order to bring a gendered perspective to judging, however it is argued that this rationale is flawed. Second, an alternative rationale based on equality and legitimacy is offered which avoids gender essentialism. While debates typically focus on these two rationales, a third rationale embraces both difference and equality/legitimacy. The presence of female judges has an important symbolic value which destabilises existing fraternal legal norms. Finally, increasing the number of female judges may not necessarily change judging, and this paper also analyses how the transformative potential offered by judicial diversity can work in practice. Elek y Rottman defienden que la evaluación judicial suele estar sesgada en contra de las mujeres y los jueces pertenecientes a minorías. La necesidad de abordar el sesgo es importante, sin embargo a menudo el deseo de diversidad parece tan evidente como para contradecir un análisis más profundo. Este artículo examina los dos motivos principales para la igualdad de género en el banquillo. En primer lugar, las mujeres jueces a menudo se consideran necesarias para aportar una perspectiva de género al hecho de juzgar, sin embargo, se defiende que este razonamiento es erróneo. En segundo lugar, se ofrece una alternativa lógica basada en la igualdad y la legitimidad que evita el esencialismo de género. Mientras que los debates suelen centrarse en estas dos razones, una tercera justificación abarca tanto la diferencia como la igualdad/legitimidad. La presencia de mujeres en la judicatura tiene un importante valor simbólico que desestabiliza las normas

  7. Sociological Perspectives.

    Science.gov (United States)

    Townley, Charles; Middleton, Mike

    This monograph examines sociological perspectives and their applications. It is intended to help the college student coming to sociology for the first time to recognize that there are several perspectives within sociology and to disentangle the mass of terms associated with each. The first distinctive sociological perspective came from the work of…

  8. An inclusive taxonomy of behavioral biases

    Directory of Open Access Journals (Sweden)

    David Peón

    2017-07-01

    Full Text Available This paper overviews the theoretical and empirical research on behavioral biases and their influence in the literature. To provide a systematic exposition, we present a unified framework that takes the reader through an original taxonomy, based on the reviews of relevant authors in the field. In particular, we establish three broad categories that may be distinguished: heuristics and biases; choices, values and frames; and social factors. We then describe the main biases within each category, and revise the main theoretical and empirical developments, linking each bias with other biases and anomalies that are related to them, according to the literature.

  9. Noise performance in AlGaN/GaN HEMTs under high drain bias

    International Nuclear Information System (INIS)

    Pang Lei; Pu Yan; Lin Xinyu; Wang Liang; Liu Jian

    2009-01-01

    The advent of fully integrated GaN PA-LNA circuits makes it meaningful to investigate the noise performance under high drain bias. However, noise performance of AlGaN/GaN HEMTs under high bias has not received worldwide attention in theoretical studies due to its complicated mechanisms. The noise value is moderately higher and its rate of increase is fast with increasing high voltage. In this paper, several possible mechanisms are proposed to be responsible for it. Impact ionization under high electric field incurs great fluctuation of carrier density, which increases the drain diffusion noise. Besides, higher gate leakage current related shot noise and a more severe self-heating effect are also contributors to the noise increase at high bias. Analysis from macroscopic and microscopic perspectives can help us to design new device structures to improve noise performance of AlGaN/GaN HEMTs under high bias. (semiconductor devices)

  10. The positivity bias in aging: Motivation or degradation?

    Science.gov (United States)

    Kalenzaga, Sandrine; Lamidey, Virginie; Ergis, Anne-Marie; Clarys, David; Piolino, Pascale

    2016-08-01

    The question of an emotional memory enhancement in aging, and of a positivity bias in particular, has been the subject of numerous empirical studies in the last decade. However, the roots of such positive preference are not yet well established. Partisans of a motivation-based perspective contend with those arguing that positivity is related to a cognitive or neural degradation. The aim of this study was to introduce some elements concerning positivity effect in aging. We compared immediate (i.e., immediate recall) versus delayed (i.e., delayed recall and recognition) emotional memory performance in 38 young adults, 39 old adults, 37 very old adults, and 41 Alzheimer's disease patients. Moreover, we manipulated the encoding instruction: Either participants received no particular processing instruction, or they had to process the material in a semantic way. The results indicated that the positivity bias is most likely to occur in individuals whose cognitive functions are preserved, after long retention delay, and in experimental conditions that do not constrain encoding. We concluded by highlighting that although these findings seem to be better in line with the motivation, rather than the degradation, perspective, they do not fully support either theory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Gender Bias Affects Forests Worldwide

    Directory of Open Access Journals (Sweden)

    Marlène Elias

    2017-04-01

    Full Text Available Gender biases persist in forestry research and practice. These biases result in reduced scientific rigor and inequitable, ineffective, and less efficient policies, programs, and interventions. Drawing from a two-volume collection of current and classic analyses on gender in forests, we outline five persistent and inter-related themes: gendered governance, tree tenure, forest spaces, division of labor, and ecological knowledge. Each emerges across geographic regions in the northern and southern hemisphere and reflects inequities in women’s and men’s ability to make decisions about and benefit from trees, forests, and their products. Women’s ability to participate in community-based forest governance is typically less than men’s, causing concern for social equity and forest stewardship. Women’s access to trees and their products is commonly more limited than men’s, and mediated by their relationship with their male counterparts. Spatial patterns of forest use reflect gender norms and taboos, and men’s greater access to transportation. The division of labor results in gender specialization in the collection of forest products, with variations in gender roles across regions. All these gender differences result in ecological knowledge that is distinct but also complementary and shifting across the genders. The ways gender plays out in relation to each theme may vary across cultures and contexts, but the influence of gender, which intersects with other factors of social differentiation in shaping forest landscapes, is global.

  12. Workplace ageism: discovering hidden bias.

    Science.gov (United States)

    Malinen, Sanna; Johnston, Lucy

    2013-01-01

    BACKGROUND/STUDY CONTEXT: Research largely shows no performance differences between older and younger employees, or that older workers even outperform younger employees, yet negative attitudes towards older workers can underpin discrimination. Unfortunately, traditional "explicit" techniques for assessing attitudes (i.e., self-report measures) have serious drawbacks. Therefore, using an approach that is novel to organizational contexts, the authors supplemented explicit with implicit (indirect) measures of attitudes towards older workers, and examined the malleability of both. This research consists of two studies. The authors measured self-report (explicit) attitudes towards older and younger workers with a survey, and implicit attitudes with a reaction-time-based measure of implicit associations. In addition, to test whether attitudes were malleable, the authors measured attitudes before and after a mental imagery intervention, where the authors asked participants in the experimental group to imagine respected and valued older workers from their surroundings. Negative, stable implicit attitudes towards older workers emerged in two studies. Conversely, explicit attitudes showed no age bias and were more susceptible to change intervention, such that attitudes became more positive towards older workers following the experimental manipulation. This research demonstrates the unconscious nature of bias against older workers, and highlights the utility of implicit attitude measures in the context of the workplace. In the current era of aging workforce and skill shortages, implicit measures may be necessary to illuminate hidden workplace ageism.

  13. Genetic profile of scrapie codons 146, 211 and 222 in the PRNP gene locus in three breeds of dairy goats.

    Science.gov (United States)

    Vouraki, Sotiria; Gelasakis, Athanasios I; Alexandri, Panoraia; Boukouvala, Evridiki; Ekateriniadou, Loukia V; Banos, Georgios; Arsenos, Georgios

    2018-01-01

    Polymorphisms at PRNP gene locus have been associated with resistance against classical scrapie in goats. Genetic selection on this gene within appropriate breeding programs may contribute to the control of the disease. The present study characterized the genetic profile of codons 146, 211 and 222 in three dairy goat breeds in Greece. A total of 766 dairy goats from seven farms were used. Animals belonged to two indigenous Greek, Eghoria (n = 264) and Skopelos (n = 287) and a foreign breed, Damascus (n = 215). Genomic DNA was extracted from blood samples from individual animals. Polymorphisms were detected in these codons using Real-Time PCR analysis and four different Custom TaqMan® SNP Genotyping Assays. Genotypic, allelic and haplotypic frequencies were calculated based on individual animal genotypes. Chi-square tests were used to examine Hardy-Weinberg equilibrium state and compare genotypic distribution across breeds. Genetic distances among the three breeds, and between these and 30 breeds reared in other countries were estimated based on haplotypic frequencies using fixation index FST with Arlequin v3.1 software; a Neighbor-Joining tree was created using PHYLIP package v3.695. Level of statistical significance was set at P = 0.01. All scrapie resistance-associated alleles (146S, 146D, 211Q and 222K) were detected in the studied population. Significant frequency differences were observed between the indigenous Greek and Damascus breeds. Alleles 222K and 146S had the highest frequency in the two indigenous and the Damascus breed, respectively (ca. 6.0%). The studied breeds shared similar haplotypic frequencies with most South Italian and Turkish breeds but differed significantly from North-Western European, Far East and some USA goat breeds. Results suggest there is adequate variation in the PRNP gene locus to support breeding programs for enhanced scrapie resistance in goats reared in Greece. Genetic comparisons among goat breeds indicate that separate

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

    Directory of Open Access Journals (Sweden)

    Metzger Kelsey J

    2010-05-01

    Full Text Available Abstract 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

  15. Methacholine PC20 In African Americans And Whites With Asthma With Homozygous Genotypes at ADRB2 Codon 16

    Science.gov (United States)

    Blake, Kathryn; Cury, James D.; Hossain, Jobayer; Tantisira, Kelan; Wang, Jianwei; Mougey, Edward; Lima, John

    2013-01-01

    BACKGROUND African Americans have worse asthma outcomes compared to whites. Adrenoceptor beta 2, surface gene (ADRB2) Gly16Arg genotypes have been associated with β2-agonist bronchodilator response, asthma exacerbation rate, response to methacholine, and lung function decline but not specifically in African Americans. OBJECTIVE We sought to compare the provocative concentration of methacholine that causes a 20% fall in FEV1 (PC20) in African Americans and whites with asthma who were ADRB2 homozygous at codon16 (Arg16Arg or Gly16Gly). METHODS African Americans and whites whose parents and grandparents were of the same race, aged ≥ 10 years, with baseline FEV1 of ≥60% predicted, and no upper or lower respiratory tract infection within the previous 2 weeks meeting genotype criteria were enrolled. PC20 was measured after withholding short-acting and long-acting β2-agonists for 8 and 12 hours respectively, montelukast for 24 hours, ipratropium bromide and inhaled corticosteroids for 12 hours, and antihistamines for 72 hours. RESULTS 423 participants were screened and 88 had a positive challenge. Participants were 32yrs ± 19yrs (mean ± SD), 70% female, 51% White (vs. African American), 6% Hispanic. Similar numbers of participants were using inhaled corticosteroids by race and genotype. There were significant differences in log PC20 between race/genotype groups (p=0.012). African American Arg16Arg participants had a lower log PC20 than White Gly16Gly (p=0.009) and African American Gly16Gly (p=0.041) participants. Both race and genotype contributed significantly to the model (p=0.037 and p=0.014, respectively) but there was no interaction between race and genotype on log PC20. CONCLUSIONS AND CLINICAL RELEVANCE Airway hyperresponsiveness is influenced by race and the ADRB2 codon 16 polymorphism. African Americans with the Arg16Arg genotype have increased airway reactivity and may be at risk for worse asthma outcomes. Inclusion of genetic information as an

  16. Approach bias modification training and consumption: A review of the literature.

    Science.gov (United States)

    Kakoschke, Naomi; Kemps, Eva; Tiggemann, Marika

    2017-01-01

    Recent theoretical perspectives and empirical evidence have suggested that biased cognitive processing is an important contributor to unhealthy behaviour. Approach bias modification is a novel intervention in which approach biases for appetitive cues are modified. The current review of the literature aimed to evaluate the effectiveness of modifying approach bias for harmful consumption behaviours, including alcohol use, cigarette smoking, and unhealthy eating. Relevant publications were identified through a search of four electronic databases (PsycINFO, Google Scholar, ScienceDirect and Scopus) that were conducted between October and December 2015. Eligibility criteria included the use of a human adult sample, at least one session of avoidance training, and an outcome measure related to the behaviour of interest. The fifteen identified publications (comprising 18 individual studies) were coded on a number of characteristics, including consumption behaviour, participants, task, training and control conditions, number of training sessions and trials, outcome measure, and results. The results generally showed positive effects of approach-avoidance training, including reduced consumption behaviour in the laboratory, lower relapse rates, and improvements in self-reported measures of behaviour. Importantly, all studies (with one exception) that reported favourable consumption outcomes also demonstrated successful reduction of the approach bias for appetitive cues. Thus, the current review concluded that approach bias modification is effective for reducing both approach bias and unhealthy consumption behaviour. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Social reward shapes attentional biases.

    Science.gov (United States)

    Anderson, Brian A

    2016-01-01

    Paying attention to stimuli that predict a reward outcome is important for an organism to survive and thrive. When visual stimuli are associated with tangible, extrinsic rewards such as money or food, these stimuli acquire high attentional priority and come to automatically capture attention. In humans and other primates, however, many behaviors are not motivated directly by such extrinsic rewards, but rather by the social feedback that results from performing those behaviors. In the present study, I examine whether positive social feedback can similarly influence attentional bias. The results show that stimuli previously associated with a high probability of positive social feedback elicit value-driven attentional capture, much like stimuli associated with extrinsic rewards. Unlike with extrinsic rewards, however, such stimuli also influence task-specific motivation. My findings offer a potential mechanism by which social reward shapes the information that we prioritize when perceiving the world around us.

  18. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2017-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...... is a general tendency to focus on numerators and pay insufficient attention to denominators in ratios. Using a population-based survey experiment, I demonstrate how differently framed but logically equivalent representations of the exact same numerical value can have large effects on citizens’ preferences...... regarding salient political issues such as education and taxes. Furthermore, the effects of numerical framing are found across most groups of the population, largely regardless of their political predisposition and their general ability to understand and use numerical information. These findings have...

  19. Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, τm5U present at 'wobble' position in anticodon loop of tRNALeu: A molecular modeling approach.

    Directory of Open Access Journals (Sweden)

    Asmita S Kamble

    Full Text Available Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm5U at the 'wobble' 34th position in tRNALeu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS. The τm5U34 specifically recognizes UUG and UUA codons. Structural consequences of τm5U34 to read cognate codons have not been studied so far in detail at the atomic level. Hence, 50ns multiple molecular dynamics (MD simulations of various anticodon stem loop (ASL models of tRNALeu in presence and absence of τm5U34 along with UUG and UUA codons were performed to explore the dynamic behaviour of τm5U34 during codon recognition process. The MD simulation results revealed that τm5U34 recognizes G/A ending codons by 'wobble' as well as a novel 'single' hydrogen bonding interactions. RMSD and RMSF values indicate the comparative stability of the ASL models containing τm5U34 modification over the other models, lacking τm5U34. Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNALeu showed crucial interactions between the A-site residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could improve our understanding about the decoding efficiency of human mt tRNALeu with τm5U34 to recognize UUG and UUA codons.

  20. Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data.

    Science.gov (United States)

    Bao, Le; Gu, Hong; Dunn, Katherine A; Bielawski, Joseph P

    2007-02-08

    Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion (AIC) or a corrected Akaike information criterion (AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure (abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene (flagellar-related proteins of Listeria). Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori

  1. Effect of Polymorphisms at Codon 146 of the Goat PRNP Gene on Susceptibility to Challenge with Classical Scrapie by Different Routes.

    Science.gov (United States)

    Papasavva-Stylianou, Penelope; Simmons, Marion Mathieson; Ortiz-Pelaez, Angel; Windl, Otto; Spiropoulos, John; Georgiadou, Soteria

    2017-11-15

    This report presents the results of experimental challenges of goats with scrapie by both the intracerebral (i.c.) and oral routes, exploring the effects of polymorphisms at codon 146 of the goat PRNP gene on resistance to disease. The results of these studies illustrate that while goats of all genotypes can be infected by i.c. challenge, the survival distribution of the animals homozygous for asparagine at codon 146 was significantly shorter than those of animals of all other genotypes (chi-square value, 10.8; P = 0.001). In contrast, only those animals homozygous for asparagine at codon 146 (NN animals) succumbed to oral challenge. The results also indicate that any cases of infection in non-NN animals can be detected by the current confirmatory test (immunohistochemistry), although successful detection with the rapid enzyme-linked immunosorbent assay (ELISA) was more variable and dependent on the polymorphism. Together with data from previous studies of goats exposed to infection in the field, these data support the previously reported observations that polymorphisms at this codon have a profound effect on susceptibility to disease. It is concluded that only animals homozygous for asparagine at codon 146 succumb to scrapie under natural conditions. IMPORTANCE In goats, like in sheep, there are PRNP polymorphisms that are associated with susceptibility or resistance to scrapie. However, in contrast to the polymorphisms in sheep, they are more numerous in goats and may be restricted to certain breeds or geographical regions. Therefore, eradication programs must be specifically designed depending on the identification of suitable polymorphisms. An initial analysis of surveillance data suggested that such a polymorphism in Cypriot goats may lie in codon 146. In this study, we demonstrate experimentally that NN animals are highly susceptible after i.c. inoculation. The presence of a D or S residue prolonged incubation periods significantly, and prions were detected

  2. Good practices for quantitative bias analysis.

    Science.gov (United States)

    Lash, Timothy L; Fox, Matthew P; MacLehose, Richard F; Maldonado, George; McCandless, Lawrence C; Greenland, Sander

    2014-12-01

    Quantitative bias analysis serves several objectives in epidemiological research. First, it provides a quantitative estimate of the direction, magnitude and uncertainty arising from systematic errors. Second, the acts of identifying sources of systematic error, writing down models to quantify them, assigning values to the bias parameters and interpreting the results combat the human tendency towards overconfidence in research results, syntheses and critiques and the inferences that rest upon them. Finally, by suggesting aspects that dominate uncertainty in a particular research result or topic area, bias analysis can guide efficient allocation of sparse research resources. The fundamental methods of bias analyses have been known for decades, and there have been calls for more widespread use for nearly as long. There was a time when some believed that bias analyses were rarely undertaken because the methods were not widely known and because automated computing tools were not readily available to implement the methods. These shortcomings have been largely resolved. We must, therefore, contemplate other barriers to implementation. One possibility is that practitioners avoid the analyses because they lack confidence in the practice of bias analysis. The purpose of this paper is therefore to describe what we view as good practices for applying quantitative bias analysis to epidemiological data, directed towards those familiar with the methods. We focus on answering questions often posed to those of us who advocate incorporation of bias analysis methods into teaching and research. These include the following. When is bias analysis practical and productive? How does one select the biases that ought to be addressed? How does one select a method to model biases? How does one assign values to the parameters of a bias model? How does one present and interpret a bias analysis?. We hope that our guide to good practices for conducting and presenting bias analyses will encourage

  3. Probing Biased Signaling in Chemokine Receptors

    DEFF Research Database (Denmark)

    Amarandi, Roxana Maria; Hjortø, Gertrud Malene; Rosenkilde, Mette Marie

    2016-01-01

    The chemokine system mediates leukocyte migration during homeostatic and inflammatory processes. Traditionally, it is described as redundant and promiscuous, with a single chemokine ligand binding to different receptors and a single receptor having several ligands. Signaling of chemokine receptors...... of others has been termed signaling bias and can accordingly be grouped into ligand bias, receptor bias, and tissue bias. Bias has so far been broadly overlooked in the process of drug development. The low number of currently approved drugs targeting the chemokine system, as well as the broad range...... of failed clinical trials, reflects the need for a better understanding of the chemokine system. Thus, understanding the character, direction, and consequence of biased signaling in the chemokine system may aid the development of new therapeutics. This review describes experiments to assess G protein...

  4. Symmetry as Bias: Rediscovering Special Relativity

    Science.gov (United States)

    Lowry, Michael R.

    1992-01-01

    This paper describes a rational reconstruction of Einstein's discovery of special relativity, validated through an implementation: the Erlanger program. Einstein's discovery of special relativity revolutionized both the content of physics and the research strategy used by theoretical physicists. This research strategy entails a mutual bootstrapping process between a hypothesis space for biases, defined through different postulated symmetries of the universe, and a hypothesis space for physical theories. The invariance principle mutually constrains these two spaces. The invariance principle enables detecting when an evolving physical theory becomes inconsistent with its bias, and also when the biases for theories describing different phenomena are inconsistent. Structural properties of the invariance principle facilitate generating a new bias when an inconsistency is detected. After a new bias is generated. this principle facilitates reformulating the old, inconsistent theory by treating the latter as a limiting approximation. The structural properties of the invariance principle can be suitably generalized to other types of biases to enable primal-dual learning.

  5. Potential of Start Codon Targeted (SCoT Markers to Estimate Genetic Diversity and Relationships among Chinese Elymus sibiricus Accessions

    Directory of Open Access Journals (Sweden)

    Junchao Zhang

    2015-04-01

    Full Text Available Elymus sibiricus as an important forage grass and gene pool for improving cereal crops, that is widely distributed in West and North China. Information on its genetic diversity and relationships is limited but necessary for germplasm collection, conservation and future breeding. Start Codon Targeted (SCoT markers were used for studying the genetic diversity and relationships among 53 E. sibiricus accessions from its primary distribution area in China. A total of 173 bands were generated from 16 SCoT primers, 159 bands of which were polymorphic with the percentage of polymorphic bands (PPB of 91.91%. Based upon population structure analysis five groups were formed. The cluster analysis separated the accessions into two major clusters and three sub-clusters, similar to results of principal coordinate analysis (PCoA. The molecular variance analysis (AMOVA showed that genetic variation was greater within geographical regions (50.99% than between them (49.01%. Furthermore, the study also suggested that collecting and evaluating E. sibiricus germplasm for major geographic regions and special environments broadens the available genetic base and illustrates the range of variation. The results of the present study showed that SCoT markers were efficient in assessing the genetic diversity among E. sibiricus accessions.

  6. c-Ha-ras BamHI RFLP in human urothelial tumors and point mutations in hot codons

    International Nuclear Information System (INIS)

    Weismanova, E; Skovraga, M.; Kaluz, S.

    1993-01-01

    High-molecular weights DNAs from 30 bladder and renal cell carcinomas (RCC) were isolated and the c-Ha-ras the c-Ha-ras gene BamHI RFLP was examined. Amplification of c-Ha-ras with normal localization with regard to the size of alleles was found only in the case. One of the normally localized c-Ha-ras allele termed RCC c-H-ras of a length of about 6.6 kbp was cloned and an oncogene-activating point mutation was identified using two restriction enzymes. After comparison of CfrI and Cfr10I cleavage maps of RCC c-Ha-ras to complete nucleotide sequences of EJ/T24 c-Ha-ras oncogene and its normal counterpart, a point mutation was identified within codon 11 or 12. The use of CfrI and Cfr10I is of value for clinical practice in identification of point mutations in c-Ha-ras PCR product in neoplasia accompanied by somatic mutation of c-Ha-ras. The correlation among c-Ha-ras allele, amplification/loss, presence of point mutation and progression of neoplasia is discussed. (author)

  7. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    Science.gov (United States)

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  8. De novo assembly and next-generation sequencing to analyse full-length gene variants from codon-barcoded libraries.

    Science.gov (United States)

    Cho, Namjin; Hwang, Byungjin; Yoon, Jung-ki; Park, Sangun; Lee, Joongoo; Seo, Han Na; Lee, Jeewon; Huh, Sunghoon; Chung, Jinsoo; Bang, Duhee

    2015-09-21

    Interpreting epistatic interactions is crucial for understanding evolutionary dynamics of complex genetic systems and unveiling structure and function of genetic pathways. Although high resolution mapping of en masse variant libraries renders molecular biologists to address genotype-phenotype relationships, long-read sequencing technology remains indispensable to assess functional relationship between mutations that lie far apart. Here, we introduce JigsawSeq for multiplexed sequence identification of pooled gene variant libraries by combining a codon-based molecular barcoding strategy and de novo assembly of short-read data. We first validate JigsawSeq on small sub-pools and observed high precision and recall at various experimental settings. With extensive simulations, we then apply JigsawSeq to large-scale gene variant libraries to show that our method can be reliably scaled using next-generation sequencing. JigsawSeq may serve as a rapid screening tool for functional genomics and offer the opportunity to explore evolutionary trajectories of protein variants.

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

    Science.gov (United States)

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

    2014-09-01

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

  10. Start codon targeted (SCoT) and target region amplification polymorphism (TRAP) for evaluating the genetic relationship of Dendrobium species.

    Science.gov (United States)

    Feng, Shangguo; He, Refeng; Yang, Sai; Chen, Zhe; Jiang, Mengying; Lu, Jiangjie; Wang, Huizhong

    2015-08-10

    Two molecular marker systems, start codon targeted (SCoT) and target region amplification polymorphism (TRAP), were used for genetic relationship analysis of 36 Dendrobium species collected from China. Twenty-two selected SCoT primers produced 337 loci, of which 324 (96%) were polymorphic, whereas 13 TRAP primer combinations produced a total of 510 loci, with 500 (97.8%) of them being polymorphic. An average polymorphism information content of 0.953 and 0.983 was detected using the SCoT and TRAP primers, respectively, showing that a high degree of genetic diversity exists among Chinese Dendrobium species. The partition of clusters in the unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis plot based on the SCoT and TRAP markers was similar and clustered the 36 Dendrobium species into four main groups. Our results will provide useful information for resource protection and will also be useful to improve the current Dendrobium breeding programs. Our results also demonstrate that SCoT and TRAP markers are informative and can be used to evaluate genetic relationships between Dendrobium species. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-05-15

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

  12. Forecaster Behaviour and Bias in Macroeconomic Forecasts

    OpenAIRE

    Roy Batchelor

    2007-01-01

    This paper documents the presence of systematic bias in the real GDP and inflation forecasts of private sector forecasters in the G7 economies in the years 1990–2005. The data come from the monthly Consensus Economics forecasting service, and bias is measured and tested for significance using parametric fixed effect panel regressions and nonparametric tests on accuracy ranks. We examine patterns across countries and forecasters to establish whether the bias reflects the inefficient use of i...

  13. An inclusive taxonomy of behavioral biases

    OpenAIRE

    David Peón; Manel Antelo; Anxo Calvo-Silvosa

    2017-01-01

    This paper overviews the theoretical and empirical research on behavioral biases and their influence in the literature. To provide a systematic exposition, we present a unified framework that takes the reader through an original taxonomy, based on the reviews of relevant authors in the field. In particular, we establish three broad categories that may be distinguished: heuristics and biases; choices, values and frames; and social factors. We then describe the main biases within each category,...

  14. Observer perspective imagery with stuttering.

    Science.gov (United States)

    Lowe, Robyn; Menzies, Ross; Packman, Ann; O'Brian, Sue; Onslow, Mark

    2015-01-01

    Adults who stutter are at risk of developing a range of psychological conditions. Social anxiety disorder is the most common anxiety disorder associated with stuttering. Observer perspective imagery is one cognitive process involved in the maintenance of some anxiety disorders. This involves viewing images as if looking at the self from the perspective of another. In contrast, the field perspective involves looking out from the self at the surrounding environment. The purpose of this study was to assess the presence of observer perspective imagery with stuttering. The authors administered the Hackmann, Surawy and Clark (1998) semi-structured interview to 30 adults who stutter and 30 controls. Group images and impressions were compared for frequency, perspective recalled and emotional valence. The stuttering group was significantly more likely than controls to recall images and impressions from an observer rather than a field perspective for anxious situations. It is possible the present results could reflect the same attentional processing bias that occurs with anxiety disorders in the non-stuttering population. These preliminary results provide an explanation for the persistence of conditions such as social anxiety disorder with stuttering. Clinical implications are discussed.

  15. Cognitive Biases and Nonverbal Cue Availability in Detecting Deception

    Science.gov (United States)

    Burgoon, Judee K.; Blair, J. Pete; Strom, Renee E.

    2008-01-01

    In potentially deceptive situations, people rely on mental shortcuts to help process information. These heuristic judgments are often biased and result in inaccurate assessments of sender veracity. Four such biases--truth bias, visual bias, demeanor bias, and expectancy violation bias--were examined in a judgment experiment that varied nonverbal…

  16. Adaptable history biases in human perceptual decisions.

    Science.gov (United States)

    Abrahamyan, Arman; Silva, Laura Luz; Dakin, Steven C; Carandini, Matteo; Gardner, Justin L

    2016-06-21

    When making choices under conditions of perceptual uncertainty, past experience can play a vital role. However, it can also lead to biases that worsen decisions. Consistent with previous observations, we found that human choices are influenced by the success or failure of past choices even in a standard two-alternative detection task, where choice history is irrelevant. The typical bias was one that made the subject switch choices after a failure. These choice history biases led to poorer performance and were similar for observers in different countries. They were well captured by a simple logistic regression model that had been previously applied to describe psychophysical performance in mice. Such irrational biases seem at odds with the principles of reinforcement learning, which would predict exquisite adaptability to choice history. We therefore asked whether subjects could adapt their irrational biases following changes in trial order statistics. Adaptability was strong in the direction that confirmed a subject's default biases, but weaker in the opposite direction, so that existing biases could not be eradicated. We conclude that humans can adapt choice history biases, but cannot easily overcome existing biases even if irrational in the current context: adaptation is more sensitive to confirmatory than contradictory statistics.

  17. Attribution bias and social anxiety in schizophrenia

    Directory of Open Access Journals (Sweden)

    Amelie M. Achim

    2016-06-01

    Full Text Available Studies on attribution biases in schizophrenia have produced mixed results, whereas such biases have been more consistently reported in people with anxiety disorders. Anxiety comorbidities are frequent in schizophrenia, in particular social anxiety disorder, which could influence their patterns of attribution biases. The objective of the present study was thus to determine if individuals with schizophrenia and a comorbid social anxiety disorder (SZ+ show distinct attribution biases as compared with individuals with schizophrenia without social anxiety (SZ− and healthy controls. Attribution biases were assessed with the Internal, Personal, and Situational Attributions Questionnaire in 41 individual with schizophrenia and 41 healthy controls. Results revealed the lack of the normal externalizing bias in SZ+, whereas SZ− did not significantly differ from healthy controls on this dimension. The personalizing bias was not influenced by social anxiety but was in contrast linked with delusions, with a greater personalizing bias in individuals with current delusions. Future studies on attribution biases in schizophrenia should carefully document symptom presentation, including social anxiety.

  18. Biased lineups: sequential presentation reduces the problem.

    Science.gov (United States)

    Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

    1991-12-01

    Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

  19. [Comparison of protective properties of the smallpox DNA-vaccine based on the variola virus A30L gene and its variant with modified codon usage].

    Science.gov (United States)

    Maksiutov, R A; Shchelkunov, S N

    2011-01-01

    Efficacy of candidate DNA-vaccines based on the variola virus natural gene A30L and artificial gene A30Lopt with modified codon usage, optimized for expression in mammalian cells, was tested. The groups of mice were intracutaneously immunized three times with three-week intervals with candidate DNA-vaccines: pcDNA_A30L or pcDNA_A30Lopt, and in three weeks after the last immunization all mice in the groups were intraperitoneally infected by the ectromelia virus K1 strain in 10 LD50 dose for the estimation of protection. It was shown that the DNA-vaccines based on natural gene A30L and codon-optimized gene A30Lopt elicited virus, thereby neutralizing the antibody response and protected mice from lethal intraperitoneal challenge with the ectromelia virus with lack of statistically significant difference.

  20. Evidence for a novel coding sequence overlapping the 5'-terminal ~90 codons of the Gill-associated and Yellow head okavirus envelope glycoprotein gene

    Directory of Open Access Journals (Sweden)

    Atkins John F

    2009-12-01

    Full Text Available Abstract The genus Okavirus (order Nidovirales includes a number of viruses that infect crustaceans, causing major losses in the shrimp industry. These viruses have a linear positive-sense ssRNA genome of ~26-27 kb, encoding a large replicase polyprotein that is expressed from the genomic RNA, and several additional proteins that are expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the envelope glycoprotein encoding sequence, ORF3, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF3. We propose that translation of the new ORF initiates at a conserved AUG codon separated by just 2 nt from the ORF3 AUG initiation codon, resulting in a novel 86 amino acid protein.

  1. Expression of chicken parvovirus VP2 in chicken embryo fibroblasts requires codon optimization for production of naked DNA and vectored meleagrid herpesvirus type 1 vaccines.

    Science.gov (United States)

    Spatz, Stephen J; Volkening, Jeremy D; Mullis, Robert; Li, Fenglan; Mercado, John; Zsak, Laszlo

    2013-10-01

    Meleagrid herpesvirus type 1 (MeHV-1) is an ideal vector for the expression of antigens from pathogenic avian organisms in order to generate vaccines. Chicken parvovirus (ChPV) is a widespread infectious virus that causes serious disease in chickens. It is one of the etiological agents largely suspected in causing Runting Stunting Syndrome (RSS) in chickens. Initial attempts to express the wild-type gene encoding the capsid protein VP2 of ChPV by insertion into the thymidine kinase gene of MeHV-1 were unsuccessful. However, transient expression of a codon-optimized synthetic VP2 gene cloned into the bicistronic vector pIRES2-Ds-Red2, could be demonstrated by immunocytochemical staining of transfected chicken embryo fibroblasts (CEFs). Red fluorescence could also be detected in these transfected cells since the red fluorescent protein gene is downstream from the internal ribosome entry site (IRES). Strikingly, fluorescence could not be demonstrated in cells transiently transfected with the bicistronic vector containing the wild-type or non-codon-optimized VP2 gene. Immunocytochemical staining of these cells also failed to demonstrate expression of wild-type VP2, indicating that the lack of expression was at the RNA level and the VP2 protein was not toxic to CEFs. Chickens vaccinated with a DNA vaccine consisting of the bicistronic vector containing the codon-optimized VP2 elicited a humoral immune response as measured by a VP2-specific ELISA. This VP2 codon-optimized bicistronic cassette was rescued into the MeHV-1 genome generating a vectored vaccine against ChPV disease.

  2. Biochemical features of genetic Creutzfeldt-Jakob disease with valine-to-isoleucine substitution at codon 180 on the prion protein gene.

    Science.gov (United States)

    Ito, Yoko; Sanjo, Nobuo; Hizume, Masaki; Kobayashi, Atsushi; Ohgami, Tetsuya; Satoh, Katsuya; Hamaguchi, Tsuyoshi; Yamada, Masahito; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro; Yokota, Takanori

    2018-02-19

    Valine-to-isoleucine substitution at codon 180 of the prion protein gene is only observed in patients with Creutzfeldt-Jakob disease and accounts for approximately half of all cases of genetic prion disease in Japan. In the present study, we investigated the biochemical characteristics of valine-to-isoleucine substitution at codon 180 in the prion protein gene, using samples obtained from the autopsied brains of seven patients with genetic Creutzfeldt-Jakob disease exhibiting this mutation (diagnoses confirmed via neuropathological examination). Among these patients, we observed an absence of diglycosylated and monoglycosylated forms of PrP res at codon 181. Our findings further indicated that the abnormal prion proteins were composed of at least three components, although smaller carboxyl-terminal fragments were predominant. Western blot analyses revealed large amounts of PrP res in the cerebral neocortices, where neuropathological examination revealed marked spongiosis. Relatively smaller amounts of PrP res were detected in the hippocampus, where milder spongiosis was observed, than in the cerebral neocortex. These findings indicate that abnormal prion proteins in the neocortex are associated with severe toxicity, resulting in severe spongiosis. Our findings further indicate that the valine-to-isoleucine substitution is not a polymorphism, but rather an authentic pathogenic mutation associated with specific biochemical characteristics that differ from those observed in sporadic Creutzfeldt-Jakob disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Genomic characteristics comparisons of 12 food-related filamentous fungi in tRNA gene set, codon usage and amino acid composition.

    Science.gov (United States)

    Chen, Wanping; Xie, Ting; Shao, Yanchun; Chen, Fusheng

    2012-04-10

    Filamentous fungi are widely exploited in food industry due to their abilities to secrete large amounts of enzymes and metabolites. The recent availability of fungal genome sequences has provided an opportunity to explore the genomic characteristics of these food-related filamentous fungi. In this paper, we selected 12 representative filamentous fungi in the areas of food processing and safety, which were Aspergillus clavatus, A. flavus, A. fumigatus, A. nidulans, A. niger, A. oryzae, A. terreus, Monascus ruber, Neurospora crassa, Penicillium chrysogenum, Rhizopus oryzae and Trichoderma reesei, and did the comparative studies of their genomic characteristics of tRNA gene distribution, codon usage pattern and amino acid composition. The results showed that the copy numbers greatly differed among isoaccepting tRNA genes and the distribution seemed to be related with translation process. The results also revealed that genome compositional variation probably constrained the base choice at the third codon, and affected the overall amino acid composition but seemed to have little effect on the integrated physicochemical characteristics of overall amino acids. The further analysis suggested that the wobble pairing and base modification were the important mechanisms in codon-anticodon interaction. In the scope of authors' knowledge, it is the first report about the genomic characteristics analysis of food-related filamentous fungi, which would be informative for the analysis of filamentous fungal genome evolution and their practical application in food industry. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Dipole-induced exchange bias.

    Science.gov (United States)

    Torres, Felipe; Morales, Rafael; Schuller, Ivan K; Kiwi, Miguel

    2017-11-09

    The discovery of dipole-induced exchange bias (EB), switching from negative to positive sign, is reported in systems where the antiferromagnet and the ferromagnet are separated by a paramagnetic spacer (AFM-PM-FM). The magnitude and sign of the EB is determined by the cooling field strength and the PM thickness. The same cooling field yields negative EB for thin spacers, and positive EB for thicker ones. The EB decay profile as a function of the spacer thickness, and the change of sign, are attributed to long-ranged dipole coupling. Our model, which accounts quantitatively for the experimental results, ignores the short range interfacial exchange interactions of the usual EB theories. Instead, it retains solely the long range dipole field that allows for the coupling of the FM and AFM across the PM spacer. The experiments allow for novel switching capabilities of long range EB systems, while the theory allows description of the structures where the FM and AFM are not in atomic contact. The results provide a new approach to design novel interacting heterostructures.

  5. Media bias under direct and indirect government control: when is the bias smaller?

    OpenAIRE

    Abhra Roy

    2015-01-01

    We present an analytical framework to compare media bias under direct and indirect government control. In this context, we show that direct control can lead to a smaller bias and higher welfare than indirect control. We further show that the size of the advertising market affects media bias only under direct control. Media bias, under indirect control, is not affected by the size of the advertising market.

  6. Developmental Changes in the Whole Number Bias

    Science.gov (United States)

    Braithwaite, David W.; Siegler, Robert S.

    2018-01-01

    Many students' knowledge of fractions is adversely affected by whole number bias, the tendency to focus on the separate whole number components (numerator and denominator) of a fraction rather than on the fraction's magnitude (ratio of numerator to denominator). Although whole number bias appears early in the fraction learning process and under…

  7. Bounding the bias of contrastive divergence learning

    DEFF Research Database (Denmark)

    Fischer, Anja; Igel, Christian

    2011-01-01

    Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k...

  8. Distinctive Characteristics of Sexual Orientation Bias Crimes

    Science.gov (United States)

    Stacey, Michele

    2011-01-01

    Despite increased attention in the area of hate crime research in the past 20 years, sexual orientation bias crimes have rarely been singled out for study. When these types of crimes are looked at, the studies are typically descriptive in nature. This article seeks to increase our knowledge of sexual orientation bias by answering the question:…

  9. Dialogue Games for Inconsistent and Biased Information

    NARCIS (Netherlands)

    Lebbink, H.J.; Witteman, C.L.M.; Meyer, J.J.C.

    2003-01-01

    In this article, a dialogue game is presented in which coherent conversational sequences with inconsistent and biased information are described at the speech act level. Inconsistent and biased information is represented with bilattice structures, and based on these bilattice structures, a

  10. Gender Bias: Inequities in the Classroom.

    Science.gov (United States)

    Love, Reeve

    1993-01-01

    This article explores sex bias in curricular materials for elementary and secondary schools. Sex bias is defined as a set of unconscious behaviors that, in themselves, are often trivial and generally favorable. Although these behaviors do not hurt if they happen only once, they can cause a great deal of harm if a pattern develops that serves to…

  11. The Battle over Studies of Faculty Bias

    Science.gov (United States)

    Gravois, John

    2007-01-01

    The American Federation of Teachers (AFT) recently commissioned a study to review the research that finds liberal bias run amok in academe. Believing that the AFT is not a dispassionate observer of this debate, this article provides "The Chronicle of Higher Education's" survey of the genre. The studies reviewed include: (1) "Political Bias in the…

  12. Production bias and cluster annihilation: Why necessary?

    DEFF Research Database (Denmark)

    Singh, B.N.; Trinkaus, H.; Woo, C.H.

    1994-01-01

    the primary cluster density is high. Therefore, a sustained high swelling rate driven by production bias must involve the annihilation of primary clusters at sinks. A number of experimental observations which are unexplainable in terms of the conventional dislocation bias for monointerstitials is considered......-field approach. The production bias approach, on the other hand, is based on the physical features of the cascade damage and is therefore considered to be more appropriate for describing the damage accumulation under cascade damage conditions. However, production bias can not produce high a swelling rate when....... It is found that the production bias and cluster annihilation are necessary to explain these observations, with, in many cases, the explicit consideration of the annihilation of the primary interstitial clusters....

  13. Distance Diffusion of Home Bias for Crowdfunding Campaigns between Categories: Insights from Data Analytics

    Directory of Open Access Journals (Sweden)

    Lihuan Guo

    2018-04-01

    Full Text Available As the information communication and investment of crowdfunding campaigns are usually accomplished online, online crowdfunding theoretically breaks the limitation of space. However, investors’ behaviors still show significant home bias; furthermore, from a dynamic view, the changes in home bias during the funding duration reflect the investment preference. This paper studies the dynamics of home bias in crowdfunding investment as well as the distance diffusion of home bias in the crowdfunding market through data mining and econometric models. The distance between investors and founders gradually increases from 3605 km to 4229 km as the funding progresses, and home bias shows different diffusion patterns between categories. For most of the campaigns, the distance between backers and founders of the successful campaigns is always greater than that of the failed ones; thus, the distance diffusion impacts the pledge results. However, the study also finds that for some categories, home bias does not play a positive role in investment or that it even shows negative impacts, among which food and technology are two extreme categories. The study provides a theoretical basis from the perspective of user behavior to analyze online investment and to improve the promotion of crowdfunding campaigns.

  14. Start Codon Targeted (SCoT) marker reveals genetic diversity of Dendrobium nobile Lindl., an endangered medicinal orchid species.

    Science.gov (United States)

    Bhattacharyya, Paromik; Kumaria, Suman; Kumar, Shrawan; Tandon, Pramod

    2013-10-15

    Genetic variability in the wild genotypes of Dendrobium nobile Lindl. collected from different parts of Northeast India, was analyzed using a Start Codon Targeted (SCoT) marker system. A total of sixty individuals comprising of six natural populations were investigated for the existing natural genetic diversity. One hundred and thirty two (132) amplicons were produced by SCoT marker generating 96.21% polymorphism. The PIC value of the SCoT marker system was 0.78 and the Rp values of the primers ranged between 4.43 and 7.50. The percentage of polymorphic loci (Pp) ranging from 25% to 56.82%, Nei's gene diversity (h) from 0.08 to 0.15 with mean Nei's gene diversity of 0.28, and Shannon's information index (I) values ranging from 0.13 to 0.24 with an average value of 0.43 were recorded. The gene flow value (0.37) and the diversity among populations (0.57) demonstrated higher genetic variation among the populations. Analysis of molecular variance (AMOVA) showed 43.37% of variation within the populations, whereas 56.63% variation was recorded among the populations. Cluster analysis also reveals high genetic variation among the genotypes. Present investigation suggests the effectiveness of SCoT marker system to estimate the genetic diversity of D. nobile and that it can be seen as a preliminary point for future research on the population and evolutionary genetics of this endangered orchid species of medicinal importance. © 2013.

  15. XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Li, Haijun; You, Yanjie; Lin, Canfeng; Zheng, Mingzhang; Hong, Chaoqun; Chen, Jiongyu; Li, Derui; Au, William W; Chen, Zhijian

    2013-01-01

    To evaluate the association between single nucleotide polymorphisms (SNPs) at the 194 and 399 codons of XRCC1, and the risk of severe acute skin and oral mucosa reactions in nasopharyngeal carcinoma patients in China. 114 patients with nasopharyngeal carcinoma were sequentially recruited in this study. Heparinized peripheral blood samples were taken for SNPs analysis before the start of radiation treatment. SNPs in XRCC1 (194Arg/Trp and 399Arg/Gln) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Dermatitis at upper neck and oral mucositis were clinically recorded according to the Common Terminology Criteria for Adverse Events v.3.0. The variant allele frequencies were 0.289 for XRCC1 194Trp and 0.263 for XRCC1 399Gln. Of the 114 patients, 24 experienced grade 3 acute dermatitis and 48 had grade 3 acute mucositis. The XRCC1 399Arg/Gln was significantly associated with the development of grade 3 dermatitis (Odds Ratio, 2.65; 95% CI, 1.04–6.73; p = 0.037, χ2 = 4.357). In addition, it was also associated with higher incidence of grade 3 mucositis with a borderline statistical significance (Odds Ratio, 2.11; 95% CI, 0.951–4.66; p = 0.065, χ2 = 3.411). The relationship between XRCC1 194Arg/Trp and acute dermatitis, and mucositis was not found. Our investigation shows, for the first time, that patients with the XRCC1 399Arg/Gln genotype were more likely to experience severe acute dermatitis and oral mucositis. With further validation, the information can be used to determine personalized radiotherapy strategy

  16. Gender bias in cardiovascular advertisements.

    Science.gov (United States)

    Ahmed, Sofia B; Grace, Sherry L; Stelfox, Henry Thomas; Tomlinson, George; Cheung, Angela M

    2004-11-01

    Women with cardiovascular disease are treated less aggressively than men. The reasons for this disparity are unclear. Pharmaceutical advertisements may influence physician practices and patient care. To determine if female and male patients are equally likely to be featured in cardiovascular advertisements. We examined all cardiovascular advertisements from US editions of general medical and cardiovascular journals published between 1 January 1996 and 30 June 1998. For each unique advertisement, we recorded the total number of journal appearances and the number of appearances in journals' premium positions. We noted the gender, age, race and role of both the primary figure and the majority of people featured in the advertisement. Nine hundred and nineteen unique cardiovascular advertisements were identified of which 254 depicted a patient as the primary figure. A total of 20%[95% confidence interval (CI) 15.3-25.5%] of these advertisements portrayed a female patient, while 80% (95% CI 74.5-84.7%) depicted a male patient, P advertisements appeared 249 times (13.3%; 95% CI 8.6-18.9%) while male patient advertisements appeared 1618 times (86.7%; 95% CI 81.1-91.4%), P advertisements also had significantly fewer mean appearances than male patient advertisements in journals' premium positions (0.82 vs. 1.99, P=0.02). Similar results were seen when the advertisements were analysed according to predominant gender. Despite increasing emphasis on cardiovascular disease in women, significant under-representation of female patients exists in cardiovascular advertisements. Physicians should be cognizant of this gender bias.

  17. Perspectives of antiferromagnetic spintronics

    Science.gov (United States)

    Jungfleisch, Matthias B.; Zhang, Wei; Hoffmann, Axel

    2018-04-01

    Antiferromagnets are promising for future spintronic applications owing to their advantageous properties: They are magnetically ordered, but neighboring magnetic moments point in opposite directions, which results in zero net magnetization. This means antiferromagnets produce no stray fields and are insensitive to external magnetic field perturbations. Furthermore, they show intrinsic high frequency dynamics, exhibit considerable spin-orbit and magneto-transport effects. Over the past decade, it has been realized that antiferromagnets have more to offer than just being utilized as passive components in exchange bias applications. This development resulted in a paradigm shift, which opens the pathway to novel concepts using antiferromagnets for spin-based technologies and applications. This article gives a broad perspective on antiferromagnetic spintronics. In particular, the manipulation and detection of antiferromagnetic states by spintronics effects, as well as spin transport and dynamics in antiferromagnetic materials will be discussed. We will also outline current challenges and future research directions in this emerging field.

  18. Bias Toward Psychodynamic Therapy: Framing the Problem and Working Toward a Solution.

    Science.gov (United States)

    Plakun, Eric M

    2017-09-01

    Although psychodynamic therapy (PDT) is an evidence-based intervention for a broad spectrum of psychiatric conditions, there is often notable bias in the way PDT is depicted both in the popular media and in the scientific literature. This has contributed to a negative view of PDT, which hampers both patient access to this treatment and researcher access to funding for further research on PDT. The adverse effects of these distortions and biases are detrimental not only to PDT but also to the overall field of psychotherapy, raising questions about its credibility. Here we summarize current evidence for PDT, describe existing biases, and formulate a set of recommendations to foster a more balanced perspective on PDT.

  19. Depressive symptoms and bias in perceived social competence among young adults.

    Science.gov (United States)

    Whitton, Sarah W; Larson, Justine J; Hauser, Stuart T

    2008-07-01

    We examined associations between depressive symptoms and young adults' self-perceptions of social competence to explore whether higher symptoms are associated with self-evaluations that are more accurate (i.e., depressive realism), negatively biased (i.e., cognitive distortion), or less accurate (i.e., self-verification perspective). In 133 young adults, depressive symptoms and discrepancies between self- and peer ratings of social competence were assessed. Results demonstrated a linear relationship between depressive symptoms and self-peer discrepancies, such that higher symptoms were associated with underestimation of the self and low symptom levels were linked with overestimation of the self relative to peer evaluations. These findings suggest negative bias in dysphorics' self-perceptions, supporting cognitive distortion models, as well as positive bias in self-perceptions of those with low depressive symptoms. Copyright 2008 Wiley Periodicals, Inc.

  20. Nonlinear bias analysis and correction of microwave temperature sounder observations for FY-3C meteorological satellite

    Science.gov (United States)

    Hu, Taiyang; Lv, Rongchuan; Jin, Xu; Li, Hao; Chen, Wenxin

    2018-01-01

    The nonlinear bias analysis and correction of receiving channels in Chinese FY-3C meteorological satellite Microwave Temperature Sounder (MWTS) is a key technology of data assimilation for satellite radiance data. The thermal-vacuum chamber calibration data acquired from the MWTS can be analyzed to evaluate the instrument performance, including radiometric temperature sensitivity, channel nonlinearity and calibration accuracy. Especially, the nonlinearity parameters due to imperfect square-law detectors will be calculated from calibration data and further used to correct the nonlinear bias contributions of microwave receiving channels. Based upon the operational principles and thermalvacuum chamber calibration procedures of MWTS, this paper mainly focuses on the nonlinear bias analysis and correction methods for improving the calibration accuracy of the important instrument onboard FY-3C meteorological satellite, from the perspective of theoretical and experimental studies. Furthermore, a series of original results are presented to demonstrate the feasibility and significance of the methods.

  1. Automation bias in electronic prescribing.

    Science.gov (United States)

    Lyell, David; Magrabi, Farah; Raban, Magdalena Z; Pont, L G; Baysari, Melissa T; Day, Richard O; Coiera, Enrico

    2017-03-16

    Clinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB. One hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured. Compared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB. This study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS.

  2. Implicit bias and its relation to health disparities: a teaching program and survey of medical students.

    Science.gov (United States)

    Gonzalez, Cristina M; Kim, Mimi Y; Marantz, Paul R

    2014-01-01

    The varying treatment of different patients by the same physician are referred to as within provider disparities. These differences can contribute to health disparities and are thought to be the result of implicit bias due to unintentional, unconscious assumptions. The purpose is to describe an educational intervention addressing both health disparities and physician implicit bias and the results of a subsequent survey exploring medical students' attitudes and beliefs toward subconscious bias and health disparities. A single session within a larger required course was devoted to health disparities and the physician's potential to contribute to health disparities through implicit bias. Following the session the students were anonymously surveyed on their Implicit Association Test (IAT) results, their attitudes and experiences regarding the fairness of the health care system, and the potential impact of their own implicit bias. The students were categorized based on whether they disagreed ("deniers") or agreed ("accepters") with the statement "Unconscious bias might affect some of my clinical decisions or behaviors." Data analysis focused specifically on factors associated with this perspective. The survey response rate was at least 69%. Of the responders, 22% were "deniers" and 77% were "accepters." Demographics between the two groups were not significantly different. Deniers were significantly more likely than accepters to report IAT results with implicit preferences toward self, to believe the IAT is invalid, and to believe that doctors and the health system provide equal care to all and were less likely to report having directly observed inequitable care. The recognition of bias cannot be taught in a single session. Our experience supports the value of teaching medical students to recognize their own implicit biases and develop skills to overcome them in each patient encounter, and in making this instruction part of the compulsory, longitudinal undergraduate

  3. Biases in GNSS-Data Processing

    Science.gov (United States)

    Schaer, S. C.; Dach, R.; Lutz, S.; Meindl, M.; Beutler, G.

    2010-12-01

    Within the Global Positioning System (GPS) traditionally different types of pseudo-range measurements (P-code, C/A-code) are available on the first frequency that are tracked by the receivers with different technologies. For that reason, P1-C1 and P1-P2 Differential Code Biases (DCB) need to be considered in a GPS data processing with a mix of different receiver types. Since the Block IIR-M series of GPS satellites also provide C/A-code on the second frequency, P2-C2 DCB need to be added to the list of biases for maintenance. Potential quarter-cycle biases between different phase observables (specifically L2P and L2C) are another issue. When combining GNSS (currently GPS and GLONASS), careful consideration of inter-system biases (ISB) is indispensable, in particular when an adequate combination of individual GLONASS clock correction results from different sources (using, e.g., different software packages) is intended. Facing the GPS and GLONASS modernization programs and the upcoming GNSS, like the European Galileo and the Chinese Compass, an increasing number of types of biases is expected. The Center for Orbit Determination in Europe (CODE) is monitoring these GPS and GLONASS related biases for a long time based on RINEX files of the tracking network of the International GNSS Service (IGS) and in the frame of the data processing as one of the global analysis centers of the IGS. Within the presentation we give an overview on the stability of the biases based on the monitoring. Biases derived from different sources are compared. Finally, we give an outlook on the potential handling of such biases with the big variety of signals and systems expected in the future.

  4. Bias in the exchange of arguments : the case of scientists' evaluation of lay viewpoints on GM food

    NARCIS (Netherlands)

    Cuppen, E.H.W.J.; Hisschemöller, M.; Midden, C.J.H.

    2009-01-01

    Most perspectives on public participation share the notion that dialogues should be open, allowing participants to articulate and evaluate different views and knowledge claims. We hypothesize that participants’ evaluation of claims may be biased because participants have a preference for a

  5. An Attitudinal Explanation of Biases in the Criminal Justice System: An Empirical Testing of Defensive Attribution Theory

    Science.gov (United States)

    Herzog, Sergio

    2008-01-01

    Theoretical perspectives, supported by empirical evidence, have consistently argued that the judicial treatment of offenders by criminal justice agents is sometimes biased by extralegal factors, such as offenders' sociodemographic characteristics. According to defensive attribution theory, individuals tend to protect themselves against unfortunate…

  6. Attentional bias in competitive situations: Winner does not take all

    Directory of Open Access Journals (Sweden)

    Zhongqiang eSun

    2015-09-01

    Full Text Available Compared to previous studies of competition with participants’ direct involvement, the current study for the first time investigated the influence of competitive outcomes on attentional bias from a perspective of an onlooker. Two simple games were employed: the Rock-Paper-Scissors game (Experiment 1 in which the outcome is based on luck, and Arm-wrestling (Experiment 2, in which the outcome is based on the competitors’ strength. After observing one of these games, participants were asked to judge a stimulus presented on either the winner’s or loser’s side of a screen. Both experiments yielded the same results, indicating that the onlookers made much quicker judgments on stimuli presented on the loser’s side than the winner’s side. This suggests the existence of an attention bias for loser-related information once a competition has ended. Our findings provide a new lens through which the influence of competition results on human cognitive processing can be understood.

  7. On the Limitations of Variational Bias Correction

    Science.gov (United States)

    Moradi, Isaac; Mccarty, Will; Gelaro, Ronald

    2018-01-01

    Satellite radiances are the largest dataset assimilated into Numerical Weather Prediction (NWP) models, however the data are subject to errors and uncertainties that need to be accounted for before assimilating into the NWP models. Variational bias correction uses the time series of observation minus background to estimate the observations bias. This technique does not distinguish between the background error, forward operator error, and observations error so that all these errors are summed up together and counted as observation error. We identify some sources of observations errors (e.g., antenna emissivity, non-linearity in the calibration, and antenna pattern) and show the limitations of variational bias corrections on estimating these errors.

  8. Cognitive biases and decision making in gambling.

    Science.gov (United States)

    Chóliz, Mariano

    2010-08-01

    Heuristics and cognitive biases can occur in reasoning and decision making. Some of them are very common in gamblers (illusion of control, representativeness, availability, etc.). Structural characteristics and functioning of games of chance favor the appearance of these biases. Two experiments were conducted with nonpathological gamblers. The first experiment was a game of dice with wagers. In the second experiment, the participants played two bingo games. Specific rules of the games favored the appearance of cognitive bias (illusion of control) and heuristics (representativeness and availability) and influence on the bets. Results and implications for gambling are discussed.

  9. Removing Malmquist bias from linear regressions

    Science.gov (United States)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  10. Reducing status quo bias in choice experiments

    DEFF Research Database (Denmark)

    Bonnichsen, Ole; Ladenburg, Jacob

    In stated preference literature, the tendency to choose the alternative representing the status quo situation seems to exceed real life status quo effects. Accordingly, status quo bias can be a problem. In Choice Experiments, status quo bias is found to be strongly correlated with protest attitudes...... toward the cost attribute. If economic values are to be elicited, this problem is difficult to remedy. In a split sample framework we test a novel ex-ante entreaty aimed specifically at the cost attribute and find that it effectively reduces status quo bias and improves the internal validity...

  11. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.

    2010-01-01

    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...... the persistent currents circulating in a superconducting loop. Analytical and numerical results indicate that the presence of fractional vortices leads to remarkable differences from the conventional case of uniformly distributed dc bias current. The theoretical findings are supported by detailed measurements...

  12. A study on investors’ personality characteristics and behavioral biases: Conservatism bias and availability bias in the Tehran Stock Exchange

    Directory of Open Access Journals (Sweden)

    Mahmoud Moradi

    2013-04-01

    Full Text Available Most economic and finance theories are based on the assumption that during economic decision making, people would act totally rational and consider all available information. Nevertheless, behavioral finance focuses on studying of the role of psychological factors on economic participants’ behavior. The study shows that in real-world environment, people are influenced by emotional and cognitive errors and may make irrational financial decisions. In many cases, the participants of financial markets are not aware of their talents for error in decision making, so they are dissatisfied with their investments by considering some behavioral biases decisions. These decisions may often yield undesirable outcomes, which could influence economy, significantly. This paper presents a survey on the relationship between personality dimensions with behavioral biases and availability bias among investment managers in the Tehran Stock Exchange using SPSS software, descriptive and inferential statistics. The necessary data are collected through questionnaire and they are analyzed using some statistical tests. The preliminary results indicate that there is a relationship between personality dimensions and behavioral biases like conservatism bias and availability bias among the investors in the Tehran Stock Exchange.

  13. A Stress-Induced Bias in the Reading of the Genetic Code in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Adi Oron-Gottesman

    2016-11-01

    Full Text Available Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a stress-induced translation machinery (STM, composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we further characterized the STM system, finding that MazF cleaves only ACA sites located in the open reading frames of processed mRNAs, while out-of-frame ACAs are resistant. This in-frame ACA cleavage of MazF seems to depend on MazF binding to an extracellular-death-factor (EDF-like element in ribosomal protein bS1 (bacterial S1, apparently causing MazF to be part of STM ribosomes. Furthermore, due to the in-frame MazF cleavage of ACAs under stress, a bias occurs in the reading of the genetic code causing the amino acid threonine to be encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA.

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

    Directory of Open Access Journals (Sweden)

    Amos J Simon

    2010-11-01

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

  15. 19F NMR studies of 5-fluorouracil-substituted Escherichia coli transfer RNAs: solution structure and codon-anticodon interaction

    International Nuclear Information System (INIS)

    Gollnick, P.D.

    1986-01-01

    19 F NMR was used to study E. coli tRNA 1 /sup Val/, tRNA/sub f//sup Met/, and tRNA/sub m//Met/, in which 5-fluorouracil (FUra) has replaced uracil and uracil-derived minor bases. 19 F NMR spectra of these tRNAs resolve resonances from nearly all the incorporated FUra residues. Each of the three tRNAs can be resolved into two isoaccepting species, termed forms A and B, whose 19 F spectra differ in the shift of one 19 F peak from ca. 4.5 ppm in form B, upfield to -15 ppm in form A. Because the two isoacceptors of each tRNA differ only at one position, the peaks at 4.5 ppm in the spectra of (FUra)tRNA 1 /sup Val/ and (FUra)tRNA/sub m//sup Met/; are assigned to FUra 17 and Fura 20 respectively. Bisulfate modification and pH dependence indicate that 19 F signals in the central region of the spectrum of (FUra)tRNA 1 /sup Val/ correspond to fluorouracils in non-base-paired regions. Photoreaction with psoralen indicates upfield 19 F signals arise from residues in helical environments. Removal of magnesium or addition of NaCl produces major, reversible changes in the 19 F spectrum of fluorinated tRNAs. Studies of manganese and spermine binding to (FUra)tRNA 1 /sup Val/ allow localization of several resonances in the 18 F spectrum to regions near putative binding sites for these ions. Binding of the codon G/sub p/U/sub p/A causes an upfield shift of a 19 F resonance at 3.9 ppm in the spectrum of (FUra)tRNA 1 /sup Val/. G/sub p/U/sub p/A/sub p/A, which is complementary to the anticodon and 5'-adjacent FUra 33, shifts an additional 19 F peak at 4.5 ppm. 1 H NMR and RNase H digestion studies show that the oligonucleotides bind to the anticodon

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

    Directory of Open Access Journals (Sweden)

    Mayorga Luis S

    2006-09-01

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

  17. Genetic polymorphisms of XRCC1 (codon 399) and susceptibility to breast cancer in Iranian women, a case-control study.

    Science.gov (United States)

    Saadat, Mostafa; Kohan, Leila; Omidvari, Shahpour

    2008-10-01

    The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. In the present study, we specifically investigated whether common genetic variant in XRCC1 (exon 10, codon Arg399Gln) was associated with an altered risk of breast cancer. The eligible cases were patients at chemotherapy unit of Nemazi hospital, Shiraz Iran, from October 1999 to August 2000 and from July 2004 to July 2005. The present study included 186 females with breast cancer. Age frequency-matched controls were randomly selected from the healthy females blood donor, according to the age distribution of the cases. A total of 187 healthy females included in the study. Using PCR-based method, the XRCC1 Arg399Gln polymorphism was determined. In control group the 399Gln allele frequency was 32.6%. The genotypic frequencies of the control subjects did not show significant deviation from Hardy-Weinberg equilibrium (chi(2) = 1.683, df = 1, P > 0.05). A statistically significant association was observed in comparison between Gln/Gln and Arg/Arg genotype (OR = 2.01, 95% CI:1.02-3.94, P = 0.041). There was no linear trend for presence of 0, 1, and 2 of the 399Gln allele and risk of breast cancer (chi(2) = 1.212, P = 0.271). In the recessive effect of the Gln allele (comparison between Gln/Gln vs. Arg/Arg+Arg/Gln), Gln/Gln genotype significantly increased the risk of breast cancer (OR = 2.31, 95% CI:1.21-4.35, P = 0.010). In the dominant effect of the Gln allele (comparison between Gln/Gln+Arg/Gln vs. Arg/Arg), Gln/Gln+Arg/Gln genotypes was not associated with the risk of breast cancer (OR = 0.95, 95% CI:0.63-1.42, P = 0.799). It is concluded that 399Gln allele may act as a recessive allele and increase the breast cancer risk.

  18. Students' gender bias in teaching evaluations

    Directory of Open Access Journals (Sweden)

    Narissra Punyanunt-Carter

    2015-09-01

    Full Text Available The goal of this study was to investigate if there is gender bias in student evaluations. Researchers administered a modified version of the teacher evaluation forms to 58 students (male=30; female=28 in a basic introductory communications class. Half the class was instructed to fill out the survey about a male professor, and the other half a female professor. Researchers broke down the evaluation results question by question in order to give a detailed account of the findings. Results revealed that there is certainly some gender bias at work when students evaluate their instructors. It was also found that gender bias does not significantly affect the evaluations. The results align with other findings in the available literature, which point to some sort of pattern regarding gender bias in evaluations, but it still seems to be inconsequential.  DOI: 10.18870/hlrc.v5i3.234

  19. Cognitive bias in symptomatic and recovered agoraphobics.

    Science.gov (United States)

    Stoler, L S; McNally, R J

    1991-01-01

    Symptomatic agoraphobics, recovered agoraphobics, and normal control subjects completed a series of sentence stems that had either ambiguous or unambiguous meanings, and had either a potentially threatening or a nonthreatening connotation. The written completions made by subjects to these stems were classified as indicating either a biased (i.e. threat-related) or unbiased interpretation of the meaning of the stem, and if a biased interpretation was made, whether the subject indicated efforts at adaptive coping with the perceived threat. Results indicated that symptomatic agoraphobics exhibited strong biases for interpreting information as threatening, relative to normal control subjects. Moreover, recovered agoraphobics resembled symptomatic agoraphobics more than normal control subjects, thus indicating that cognitive biases may persist following cessation of panic attacks and reductions in avoidance behavior. However, recovered agoraphobics also exhibited tendencies to cope adaptively with perceived threats whereas symptomatic agoraphobics did not.

  20. Galaxy bias and primordial non-Gaussianity

    Energy Technology Data Exchange (ETDEWEB)

    Assassi, Valentin; Baumann, Daniel [DAMTP, Cambridge University, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Schmidt, Fabian, E-mail: assassi@ias.edu, E-mail: D.D.Baumann@uva.nl, E-mail: fabians@MPA-Garching.MPG.DE [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, 85748 Garching (Germany)

    2015-12-01

    We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin of any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation.

  1. Accounting for Unobservable Exposure Time Bias Wh...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Accounting for Unobservable Exposure Time Bias When Using Medicare Prescription Drug Data Unobservable exposure time is common among Medicare Part D beneficiaries,...

  2. Galaxy bias and primordial non-Gaussianity

    International Nuclear Information System (INIS)

    Assassi, Valentin; Baumann, Daniel; Schmidt, Fabian

    2015-01-01

    We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin of any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation

  3. Exchange bias studied with polarized neutron reflectivity

    International Nuclear Information System (INIS)

    Velthuis, S. G. E. te

    2000-01-01

    The role of Polarized Neutron Reflectivity (PNR) for studying natural and synthetic exchange biased systems is illustrated. For a partially oxidized thin film of Co, cycling of the magnetic field causes a considerable reduction of the bias, which the onset of diffuse neutron scattering shows to be due to the loosening of the ferromagnetic domains. On the other hand, PNR measurements of a model exchange bias junction consisting of an n-layered Fe/Cr antiferromagnetic (AF) superlattice coupled with an m-layered Fe/Cr ferromagnetic (F) superlattice confirm the predicted collinear magnetization in the two superlattices. The two magnetized states of the F (along or opposite to the bias field) differ only in the relative orientation of the F and adjacent AF layer. The possibility of reading clearly the magnetic state at the interface pinpoints the commanding role that PNR is having in solving this intriguing problem

  4. Fixed points of occasionally weakly biased mappings

    OpenAIRE

    Y. Mahendra Singh, M. R. Singh

    2012-01-01

    Common fixed point results due to Pant et al. [Pant et al., Weak reciprocal continuity and fixed point theorems, Ann Univ Ferrara, 57(1), 181-190 (2011)] are extended to a class of non commuting operators called occasionally weakly biased pair[ N. Hussain, M. A. Khamsi A. Latif, Commonfixed points for JH-operators and occasionally weakly biased pairs under relaxed conditions, Nonlinear Analysis, 74, 2133-2140 (2011)]. We also provideillustrative examples to justify the improvements. Abstract....

  5. The Local Bias of Individual Investors

    OpenAIRE

    Ning Zhu

    2002-01-01

    This study investigates individual investors' bias towards nearby companies. Using data from a large U.S. discount brokerage, we find that individual investors tend to invest in companies closer to them relative to the market portfolio. Unlike Coval and Moskowitz's (1999) findings on institutional investors, however, we find that advantageous information cannot explain individual investors' local bias. Accounting numbers and information asymmetry matter less to individual investors' local bia...

  6. GENDER DIFFERENCES AND BIASES IN THE WORKPLACE

    OpenAIRE

    Shruti Srivastava*1 & Dr. Shweta S. Kulshrestha2

    2018-01-01

    Gender equality in the workplace has been a major concern for almost all the organizations and countries. Even in most developed countries we cannot find complete gender equality in true sense. This paper aims to discuss whether there is gender biasness in organizations or not? Gender biasness is considered as a major constraint towards the development process in any of the country and thus we have made an attempt to determine the root causes for gender gap that persists in our society. A...

  7. Systematic biases in human heading estimation.

    Directory of Open Access Journals (Sweden)

    Luigi F Cuturi

    Full Text Available Heading estimation is vital to everyday navigation and locomotion. Despite extensive behavioral and physiological research on both visual and vestibular heading estimation over more than two decades, the accuracy of heading estimation has not yet been systematically evaluated. Therefore human visual and vestibular heading estimation was assessed in the horizontal plane using a motion platform and stereo visual display. Heading angle was overestimated during forward movements and underestimated during backward movements in response to both visual and vestibular stimuli, indicating an overall multimodal bias toward lateral directions. Lateral biases are consistent with the overrepresentation of lateral preferred directions observed in neural populations that carry visual and vestibular heading information, including MSTd and otolith afferent populations. Due to this overrepresentation, population vector decoding yields patterns of bias remarkably similar to those observed behaviorally. Lateral biases are inconsistent with standard bayesian accounts which predict that estimates should be biased toward the most common straight forward heading direction. Nevertheless, lateral biases may be functionally relevant. They effectively constitute a perceptual scale expansion around straight ahead which could allow for more precise estimation and provide a high gain feedback signal to facilitate maintenance of straight-forward heading during everyday navigation and locomotion.

  8. Domain wall engineering through exchange bias

    International Nuclear Information System (INIS)

    Albisetti, E.; Petti, D.

    2016-01-01

    The control of the structure and position of magnetic domain walls is at the basis of the development of different magnetic devices and architectures. Several nanofabrication techniques have been proposed to geometrically confine and shape domain wall structures; however, a fine tuning of the position and micromagnetic configuration is hardly achieved, especially in continuous films. This work shows that, by controlling the unidirectional anisotropy of a continuous ferromagnetic film through exchange bias, domain walls whose spin arrangement is generally not favored by dipolar and exchange interactions can be created. Micromagnetic simulations reveal that the domain wall width, position and profile can be tuned by establishing an abrupt change in the direction and magnitude of the exchange bias field set in the system. - Highlights: • Micromagnetic simulations study domain walls in exchange biased thin films. • Novel domain wall configurations can be stabilized via exchange bias. • Domain walls nucleate at the boundary of regions with different exchange bias. • Domain wall width and spin profile are controlled by tuning the exchange bias.

  9. The p53 codon 72 PRO/PRO genotype may be associated with initial central visual field defects in caucasians with primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Janey L Wiggs

    Full Text Available Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg and the subset of primary open angle glaucoma (POAG patients with early loss of central visual field.Genotypes for the p53 codon 72 polymorphism (Pro/Arg were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST. The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral. All cases and controls were Caucasian with European ancestry.The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p=2.7 × 10(-5. We replicated this finding in the GIST cohort (p  =7.3 × 10(-3, and in the pooled sample (p=6.6 × 10(-7 and in a meta-analysis of both the US and GIST datasets (1.3 × 10(-6, OR 2.17 (1.58-2.98 for the PRO allele.These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.

  10. HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy.

    Science.gov (United States)

    Estep, Anne L; Tidyman, William E; Teitell, Michael A; Cotter, Philip D; Rauen, Katherine A

    2006-01-01

    Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Based on similarities with other cancer syndromes, we previously hypothesized that CS is likely due to activation of signal transduction through the Ras/MAPK pathway [Tartaglia et al., 2003]. In this study, the HRAS coding region was sequenced for mutations in a large, well-characterized cohort of 36 CS patients. Heterogeneous missense point mutations predicting an amino acid substitution were identified in 33/36 (92%) patients. The majority (91%) had a 34G --> A transition in codon 12. Less frequent mutations included 35G --> C (codon 12) and 37G --> T (codon 13). Parental samples did not have an HRAS mutation supporting the hypothesis of de novo heterogeneous mutations. There is phenotypic variability among patients with a 34G --> A transition. The most consistent features included characteristic facies and skin, failure to thrive, developmental delay, musculoskeletal abnormalities, visual impairment, cardiac abnormalities, and generalized hyperpigmentation. The two patients with 35G --> C had cardiac arrhythmias whereas one patient with a 37G --> T transversion had an enlarged aortic root. Of the patients with a clinical diagnosis of CS, neoplasia was the most consistent phenotypic feature for predicating an HRAS mutation. To gain an understanding of the relationship between constitutional HRAS mutations and malignancy, HRAS was sequenced in an advanced biphasic rhabdomyosarcoma/fibrosarcoma from an individual with a 34G --> A mutation. Loss of the wild-type HRAS allele was observed, suggesting tumorigenesis in CS patients is accompanied by additional somatic changes affecting HRAS. Finally, due to phenotypic overlap between CS and cardio-facio-cutaneous (CFC) syndromes, the HRAS coding region was sequenced in a well-characterized CFC cohort

  11. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    Science.gov (United States)

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  13. Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315.

    Directory of Open Access Journals (Sweden)

    Rose E Jeeves

    Full Text Available An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity. We addressed this question by observing populations of either slow growing (constant 69.3h mean generation time or fast growing bacilli (constant 23.1h mean generation time in their response to the effects of isoniazid exposure, using controlled and defined growth in chemostats. Phenotypic differences were detected between the populations at the two growth rates including expression of efflux mechanisms and the involvement of antisense RNA/small RNA in the regulation of a drug-tolerant phenotype, which has not been explored previously for M. tuberculosis. Genotypic analyses showed that slow growing bacilli develop resistance to isoniazid through mutations specifically in katG codon Ser315 which are present in approximately 50-90% of all isoniazid-resistant clinical isolates. The fast growing bacilli persisted as a mixed population with katG mutations distributed throughout the gene. Mutations in katG codon Ser315 appear to have a fitness cost in vitro and particularly in fast growing cultures. Our results suggest a requirement for functional katG-encoded catalase-peroxide in the slow growers but not the fast-growing bacteria, which may explain why katG codon Ser315 mutations are favoured in the slow growing cultures.

  14. Determination and Correction of Persistent Biases in Quantum Annealers

    Science.gov (United States)

    2016-08-25

    for all of the qubits. Narrowing of the bias distribution. To show the correctability of the persistent biases , we ran the experiment described above...this is a promising application for bias correction . Importantly, while the J biases determined here are in general smaller than the h biases , numerical...1Scientific RepoRts | 6:18628 | DOI: 10.1038/srep18628 www.nature.com/scientificreports Determination and correction of persistent biases in quantum

  15. Looking into the future: An inward bias in aesthetic experience driven only by gaze cues.

    Science.gov (United States)

    Chen, Yi-Chia; Colombatto, Clara; Scholl, Brian J

    2018-07-01

    The inward bias is an especially powerful principle of aesthetic experience: In framed images (e.g. photographs), we prefer peripheral figures that face inward (vs. outward). Why does this bias exist? Since agents tend to act in the direction in which they are facing, one intriguing possibility is that the inward bias reflects a preference to view scenes from a perspective that will allow us to witness those predicted future actions. This account has been difficult to test with previous displays, in which facing direction is often confounded with either global shape profiles or the relative locations of salient features (since e.g. someone's face is generally more visually interesting than the back of their head). But here we demonstrate a robust inward bias in aesthetic judgment driven by a cue that is socially powerful but visually subtle: averted gaze. Subjects adjusted the positions of people in images to maximize the images' aesthetic appeal. People with direct gaze were not placed preferentially in particular regions, but people with averted gaze were reliably placed so that they appeared to be looking inward. This demonstrates that the inward bias can arise from visually subtle features, when those features signal how future events may unfold. Copyright © 2018. Published by Elsevier B.V.

  16. Beyond assembly bias: exploring secondary halo biases for cluster-size haloes

    Science.gov (United States)

    Mao, Yao-Yuan; Zentner, Andrew R.; Wechsler, Risa H.

    2018-03-01

    Secondary halo bias, commonly known as `assembly bias', is the dependence of halo clustering on a halo property other than mass. This prediction of the Λ Cold Dark Matter cosmology is essential to modelling the galaxy distribution to high precision and interpreting clustering measurements. As the name suggests, different manifestations of secondary halo bias have been thought to originate from halo assembly histories. We show conclusively that this is incorrect for cluster-size haloes. We present an up-to-date summary of secondary halo biases of high-mass haloes due to various halo properties including concentration, spin, several proxies of assembly history, and subhalo properties. While concentration, spin, and the abundance and radial distribution of subhaloes exhibit significant secondary biases, properties that directly quantify halo assembly history do not. In fact, the entire assembly histories of haloes in pairs are nearly identical to those of isolated haloes. In general, a global correlation between two halo properties does not predict whether or not these two properties exhibit similar secondary biases. For example, assembly history and concentration (or subhalo abundance) are correlated for both paired and isolated haloes, but follow slightly different conditional distributions in these two cases. This results in a secondary halo bias due to concentration (or subhalo abundance), despite the lack of assembly bias in the strict sense for cluster-size haloes. Due to this complexity, caution must be exercised in using any one halo property as a proxy to study the secondary bias due to another property.

  17. Affective Biases in Humans and Animals.

    Science.gov (United States)

    Robinson, E S J; Roiser, J P

    Depression is one of the most common but poorly understood psychiatric conditions. Although drug treatments and psychological therapies are effective in some patients, many do not achieve full remission and some patients receive no apparent benefit. Developing new improved treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in pre-clinical studies. Recent developments in our understanding of the basic cognitive processes that may contribute to the development of depression and its treatment offer new opportunities for both clinical and pre-clinical research. This chapter discusses the clinical evidence supporting a cognitive neuropsychological model of depression and antidepressant efficacy, and how this information may be usefully translated to pre-clinical investigation. Studies using neuropsychological tests in depressed patients and at risk populations have revealed basic negative emotional biases and disrupted reward and punishment processing, which may also impact on non-affective cognition. These affective biases are sensitive to antidepressant treatments with early onset effects observed, suggesting an important role in recovery. This clinical work into affective biases has also facilitated back-translation to animals and the development of assays to study affective biases in rodents. These animal studies suggest that, similar to humans, rodents in putative negative affective states exhibit negative affective biases on decision-making and memory tasks. Antidepressant treatments also induce positive biases in these rodent tasks, supporting the translational validity of this approach. Although still in the early stages of development and validation, affective biases in depression have the potential to offer new insights into the clinical condition, as well as facilitating the development of more translational approaches for pre-clinical studies.

  18. Does social distance modulate adults' egocentric biases when reasoning about false beliefs?

    Science.gov (United States)

    Farrar, Benjamin G; Ostojić, Ljerka

    2018-01-01

    When given privileged information of an object's true location, adults often overestimate the likelihood that a protagonist holding a false belief will search in the correct location for that object. This type of egocentric bias is often labelled the 'curse of knowledge'. Interestingly, the magnitude of this bias may be modulated by the social distance between the perspective taker and target. However, this social distance effect has yet to be fully demonstrated when adults reason about false beliefs. Using a continuous false belief task, we investigated i) whether adults were biased by their own knowledge when reasoning about another's false belief, ii) whether the magnitude of this egocentric bias was modulated by social distance, and iii) whether this social distance effect extended to a heterospecific out-group, namely a dog. To test these hypotheses we conducted three experiments. In Experiment 1 (N = 283), we used an established continuous false belief task, in Experiment 2 (N = 281) we modified this task, and Experiment 3 (N = 744) was a direct replication of Experiment 2. Across these experiments, the curse of knowledge effect was reliably replicated when adults mentalised about an in-group protagonist, and replicated in two of the three studies (Experiments 1 and 3) when adults mentalised about out-group protagonists. In an internal-meta analysis, the curse of knowledge effect was present across all conditions, and there was no effect of social distance. Hence, overall these data are not consistent with the hypothesis that social distance modulates adults' egocentric biases when reasoning about false beliefs. The finding that egocentric biases of a similar magnitude were observed when adults mentalised about an in-group protagonist and a dog suggests that interpersonal dissimilarity is not in itself sufficient to reduce egocentric bias when reasoning about false beliefs.

  19. On the relative independence of thinking biases and cognitive ability.

    Science.gov (United States)

    Stanovich, Keith E; West, Richard F

    2008-04-01

    In 7 different studies, the authors observed that a large number of thinking biases are uncorrelated with cognitive ability. These thinking biases include some of the most classic and well-studied biases in the heuristics and biases literature, including the conjunction effect, framing effects, anchoring effects, outcome bias, base-rate neglect, "less is more" effects, affect biases, omission bias, myside bias, sunk-cost effect, and certainty effects that violate the axioms of expected utility theory. In a further experiment, the authors nonetheless showed that cognitive ability does correlate with the tendency to avoid some rational thinking biases, specifically the tendency to display denominator neglect, probability matching rather than maximizing, belief bias, and matching bias on the 4-card selection task. The authors present a framework for predicting when cognitive ability will and will not correlate with a rational thinking tendency. (c) 2008 APA, all rights reserved.

  20. Intermodel spread of the double-ITCZ bias in coupled GCMs tied to land surface temperature in AMIP GCMs

    Science.gov (United States)

    Zhou, Wenyu; Xie, Shang-Ping

    2017-08-01

    Global climate models (GCMs) have long suffered from biases of excessive tropical precipitation in the Southern Hemisphere (SH). The severity of the double-Intertropical Convergence Zone (ITCZ) bias, defined here as the interhemispheric difference in zonal mean tropical precipitation, varies strongly among models in the Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble. Models with a more severe double-ITCZ bias feature warmer tropical sea surface temperature (SST) in the SH, coupled with weaker southeast trades. While previous studies focus on coupled ocean-atmosphere interactions, here we show that the intermodel spread in the severity of the double-ITCZ bias is closely related to land surface temperature biases, which can be further traced back to those in the Atmosphere Model Intercomparison Project (AMIP) simulations. By perturbing land temperature in models, we demonstrate that cooler land can indeed lead to a more severe double-ITCZ bias by inducing the above coupled SST-trade wind pattern in the tropics. The response to land temperature can be consistently explained from both the dynamic and energetic perspectives. Although this intermodel spread from the land temperature variation does not account for the ensemble model mean double-ITCZ bias, identifying the land temperature effect provides insights into simulating a realistic ITCZ for the right reasons.

  1. Non-Gaussian halo assembly bias

    International Nuclear Information System (INIS)

    Reid, Beth A.; Verde, Licia; Dolag, Klaus; Matarrese, Sabino; Moscardini, Lauro

    2010-01-01

    The strong dependence of the large-scale dark matter halo bias on the (local) non-Gaussianity parameter, f NL , offers a promising avenue towards constraining primordial non-Gaussianity with large-scale structure surveys. In this paper, we present the first detection of the dependence of the non-Gaussian halo bias on halo formation history using N-body simulations. We also present an analytic derivation of the expected signal based on the extended Press-Schechter formalism. In excellent agreement with our analytic prediction, we find that the halo formation history-dependent contribution to the non-Gaussian halo bias (which we call non-Gaussian halo assembly bias) can be factorized in a form approximately independent of redshift and halo mass. The correction to the non-Gaussian halo bias due to the halo formation history can be as large as 100%, with a suppression of the signal for recently formed halos and enhancement for old halos. This could in principle be a problem for realistic galaxy surveys if observational selection effects were to pick galaxies occupying only recently formed halos. Current semi-analytic galaxy formation models, for example, imply an enhancement in the expected signal of ∼ 23% and ∼ 48% for galaxies at z = 1 selected by stellar mass and star formation rate, respectively

  2. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

    Directory of Open Access Journals (Sweden)

    Niranjan Y. Sardesai

    2013-07-01

    Full Text Available Lassa virus (LASV causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC that expressed the LASV glycoprotein precursor gene (GPC. This plasmid was used to vaccinate guinea pigs (GPs using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6 with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

  3. Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

    Science.gov (United States)

    Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

    2011-09-01

    Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

  4. Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

    Science.gov (United States)

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

    2016-01-01

    Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

  5. Hindsight bias and outcome bias in the social construction of medical negligence: a review.

    Science.gov (United States)

    Hugh, Thomas B; Dekker, Sidney W A

    2009-05-01

    Medical negligence has been the subject of much public debate in recent decades. Although the steep increase in the frequency and size of claims against doctors at the end of the last century appears to have plateaued, in Australia at least, medical indemnity costs and consequences are still a matter of concern for doctors, medical defence organisations and governments in most developed countries. Imprecision in the legal definition of negligence opens the possibility that judgments of this issue at several levels may be subject to hindsight and outcome bias. Hindsight bias relates to the probability of an adverse event perceived by a retrospective observer ("I would have known it was going to happen"), while outcome bias is a largely subconscious cognitive distortion produced by the observer's knowledge of the adverse outcome. This review examines the relevant legal, medical, psychological and sociological literature on the operation of these pervasive and universal biases in the retrospective evaluation of adverse events. A finding of medical negligence is essentially an after-the-event social construction and is invariably affected by hindsight bias and knowledge of the adverse outcome. Such biases obviously pose a threat to the fairness of judgments. A number of debiasing strategies have been suggested but are relatively ineffective because of the universality and strength of these biases and the inherent difficulty of concealing from expert witnesses knowledge of the outcome. Education about the effect of the biases is therefore important for lawyers, medical expert witnesses and the judiciary.

  6. Attention bias modification training under working memory load increases the magnitude of change in attentional bias.

    Science.gov (United States)

    Clarke, Patrick J F; Branson, Sonya; Chen, Nigel T M; Van Bockstaele, Bram; Salemink, Elske; MacLeod, Colin; Notebaert, Lies

    2017-12-01

    Attention bias modification (ABM) procedures have shown promise as a therapeutic intervention, however current ABM procedures have proven inconsistent in their ability to reliably achieve the requisite change in attentional bias needed to produce emotional benefits. This highlights the need to better understand the precise task conditions that facilitate the intended change in attention bias in order to realise the therapeutic potential of ABM procedures. Based on the observation that change in attentional bias occurs largely outside conscious awareness, the aim of the current study was to determine if an ABM procedure delivered under conditions likely to preclude explicit awareness of the experimental contingency, via the addition of a working memory load, would contribute to greater change in attentional bias. Bias change was assessed among 122 participants in response to one of four ABM tasks given by the two experimental factors of ABM training procedure delivered either with or without working memory load, and training direction of either attend-negative or avoid-negative. Findings revealed that avoid-negative ABM procedure under working memory load resulted in significantly greater reductions in attentional bias compared to the equivalent no-load condition. The current findings will require replication with clinical samples to determine the utility of the current task for achieving emotional benefits. These present findings are consistent with the position that the addition of a working memory load may facilitate change in attentional bias in response to an ABM training procedure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Research bias in judgement bias studies : a systematic review of valuation judgement literature

    NARCIS (Netherlands)

    Vincent Gruis; Pim Klamer; Cok Bakker

    2017-01-01

    Valuation judgement bias has been a research topic for several years due to its proclaimed effect on valuation accuracy. However, little is known on the emphasis of literature on judgement bias, with regard to, for instance, research methodologies, research context and robustness of research

  8. Research bias in judgement bias studies : A systematic review of valuation judgement literature

    NARCIS (Netherlands)

    Klamer, Pim; Bakker, C.; Gruis, Vincent

    2017-01-01

    Valuation judgement bias has been a research topic for several years due to its proclaimed effect on valuation accuracy. However, little is known on the emphasis of literature on judgement bias, with regard to, for instance, research methodologies, research context and robustness of research

  9. Placebo effect studies are susceptible to response bias and to other types of biases

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Kaptchuk, Ted J; Miller, Franklin G

    2011-01-01

    Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo....

  10. Toward a synthesis of cognitive biases: how noisy information processing can bias human decision making.

    Science.gov (United States)

    Hilbert, Martin

    2012-03-01

    A single coherent framework is proposed to synthesize long-standing research on 8 seemingly unrelated cognitive decision-making biases. During the past 6 decades, hundreds of empirical studies have resulted in a variety of rules of thumb that specify how humans systematically deviate from what is normatively expected from their decisions. Several complementary generative mechanisms have been proposed to explain those cognitive biases. Here it is suggested that (at least) 8 of these empirically detected decision-making biases can be produced by simply assuming noisy deviations in the memory-based information processes that convert objective evidence (observations) into subjective estimates (decisions). An integrative framework is presented to show how similar noise-based mechanisms can lead to conservatism, the Bayesian likelihood bias, illusory correlations, biased self-other placement, subadditivity, exaggerated expectation, the confidence bias, and the hard-easy effect. Analytical tools from information theory are used to explore the nature and limitations that characterize such information processes for binary and multiary decision-making exercises. The ensuing synthesis offers formal mathematical definitions of the biases and their underlying generative mechanism, which permits a consolidated analysis of how they are related. This synthesis contributes to the larger goal of creating a coherent picture that explains the relations among the myriad of seemingly unrelated biases and their potential psychological generative mechanisms. Limitations and research questions are discussed.

  11. A Comparison of attentional biases and memory biases in social phobia and major depression

    NARCIS (Netherlands)

    Rinck, M.; Becker, E.S.

    2005-01-01

    Cognitive processes play an important role in the etiology and maintenance of anxiety and depression. Current theories differ, however, in their predictions regarding the occurrence of attentional biases and memory biases in depression and anxiety. To allow for a systematic comparison of disorders

  12. Recognition bias and the physical attractiveness stereotype.

    Science.gov (United States)

    Rohner, Jean-Christophe; Rasmussen, Anders

    2012-06-01

    Previous studies have found a recognition bias for information consistent with the physical attractiveness stereotype (PAS), in which participants believe that they remember that attractive individuals have positive qualities and that unattractive individuals have negative qualities, regardless of what information actually occurred. The purpose of this research was to examine whether recognition bias for PAS congruent information is replicable and invariant across a variety of conditions (i.e. generalizable). The effects of nine different moderator variables were examined in two experiments. With a few exceptions, the effect of PAS congruence on recognition bias was independent of the moderator variables. The results suggest that the tendency to believe that one remembers information consistent with the physical attractiveness stereotype is a robust phenomenon. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  13. Systematic approach to establishing criticality biases

    International Nuclear Information System (INIS)

    Larson, S.L.

    1995-09-01

    A systematic approach has been developed to determine benchmark biases and apply those biases to code results to meet the requirements of DOE Order 5480.24 regarding documenting criticality safety margins. Previously, validation of the code against experimental benchmarks to prove reasonable agreement was sufficient. However, DOE Order 5480.24 requires contractors to adhere to the requirements of ANSI/ANS-8.1 and establish subcritical margins. A method was developed to incorporate biases and uncertainties from benchmark calculations into a k eff value with quantifiable uncertainty. The method produces a 95% confidence level in both the k eff value of the scenario modeled and the distribution of the k eff S calculated by the Monte Carlo code. Application of the method to a group of benchmarks modeled using the KENO-Va code and the SCALE 27 group cross sections is also presented

  14. Optimism Bias in Fans and Sports Reporters.

    Science.gov (United States)

    Love, Bradley C; Kopeć, Łukasz; Guest, Olivia

    2015-01-01

    People are optimistic about their prospects relative to others. However, existing studies can be difficult to interpret because outcomes are not zero-sum. For example, one person avoiding cancer does not necessitate that another person develops cancer. Ideally, optimism bias would be evaluated within a closed formal system to establish with certainty the extent of the bias and the associated environmental factors, such that optimism bias is demonstrated when a population is internally inconsistent. Accordingly, we asked NFL fans to predict how many games teams they liked and disliked would win in the 2015 season. Fans, like ESPN reporters assigned to cover a team, were overly optimistic about their team's prospects. The opposite pattern was found for teams that fans disliked. Optimism may flourish because year-to-year team results are marked by auto-correlation and regression to the group mean (i.e., good teams stay good, but bad teams improve).

  15. Optimism Bias in Fans and Sports Reporters

    Science.gov (United States)

    Love, Bradley C.

    2015-01-01

    People are optimistic about their prospects relative to others. However, existing studies can be difficult to interpret because outcomes are not zero-sum. For example, one person avoiding cancer does not necessitate that another person develops cancer. Ideally, optimism bias would be evaluated within a closed formal system to establish with certainty the extent of the bias and the associated environmental factors, such that optimism bias is demonstrated when a population is internally inconsistent. Accordingly, we asked NFL fans to predict how many games teams they liked and disliked would win in the 2015 season. Fans, like ESPN reporters assigned to cover a team, were overly optimistic about their team’s prospects. The opposite pattern was found for teams that fans disliked. Optimism may flourish because year-to-year team results are marked by auto-correlation and regression to the group mean (i.e., good teams stay good, but bad teams improve). PMID:26352146

  16. Motion, identity and the bias toward agency

    Directory of Open Access Journals (Sweden)

    Chris eFields

    2014-08-01

    Full Text Available The well-documented human bias toward agency as a cause and therefore an explanation of observed events is typically attributed to evolutionary selection for a social brain. Based on a review of developmental and adult behavioral and neurocognitive data, it is argued that the bias toward agency is a result of the default human solution, developed during infancy, to the computational requirements of object re-identification over gaps in observation of more than a few seconds. If this model is correct, overriding the bias toward agency to construct mechanistic explanations of observed events requires structure-mapping inferences, implemented by the pre-motor action planning system, that replace agents with mechanisms as causes of unobserved changes in contextual or featural properties of objects. Experiments that would test this model are discussed.

  17. A system for biasing a differential amplifier

    International Nuclear Information System (INIS)

    Barbier, Daniel; Ittel, J.M.; Poujois, Robert

    1975-01-01

    This invention concerns a system for biasing a differential amplifier. It particularly applies to the integrated differential amplifiers designed with MOS field effect transistors. Variations in the technological parameters may well cause the amplifying transistors to work outside their usual operational area, in other words outside the linear part of the transfer characteristic. To ensure that these transistors function correctly, it is necessary that the value of the voltage difference at the output be equally null. To do this and to centre on the so called 'rest' point of the amplifier transfer charateristic, the condition will be set that the output potentials of each amplifier transistor should have a zero value or a constant value as sum. With this in view, the bias on the source (generally a transistor powered by its grid bias voltage) supplying current to the two amplifying transistors fitted in parallel, is permanently adjusted in a suitable manner [fr

  18. Using Machine Learning to Predict MCNP Bias

    Energy Technology Data Exchange (ETDEWEB)

    Grechanuk, Pavel Aleksandrovi [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-01-09

    For many real-world applications in radiation transport where simulations are compared to experimental measurements, like in nuclear criticality safety, the bias (simulated - experimental keff) in the calculation is an extremely important quantity used for code validation. The objective of this project is to accurately predict the bias of MCNP6 [1] criticality calculations using machine learning (ML) algorithms, with the intention of creating a tool that can complement the current nuclear criticality safety methods. In the latest release of MCNP6, the Whisper tool is available for criticality safety analysts and includes a large catalogue of experimental benchmarks, sensitivity profiles, and nuclear data covariance matrices. This data, coming from 1100+ benchmark cases, is used in this study of ML algorithms for criticality safety bias predictions.

  19. Beyond attentional bias: a perceptual bias in a dot-probe task.

    Science.gov (United States)

    Bocanegra, Bruno R; Huijding, Jorg; Zeelenberg, René

    2012-12-01

    Previous dot-probe studies indicate that threat-related face cues induce a bias in spatial attention. Independently of spatial attention, a recent psychophysical study suggests that a bilateral fearful face cue improves low spatial-frequency perception (LSF) and impairs high spatial-frequency perception (HSF). Here, we combine these separate lines of research within a single dot-probe paradigm. We found that a bilateral fearful face cue, compared with a bilateral neutral face cue, speeded up responses to LSF targets and slowed down responses to HSF targets. This finding is important, as it shows that emotional cues in dot-probe tasks not only bias where information is preferentially processed (i.e., an attentional bias in spatial location), but also bias what type of information is preferentially processed (i.e., a perceptual bias in spatial frequency). PsycINFO Database Record (c) 2012 APA, all rights reserved.

  20. Biasing of Capacitive Micromachined Ultrasonic Transducers.

    Science.gov (United States)

    Caliano, Giosue; Matrone, Giulia; Savoia, Alessandro Stuart

    2017-02-01

    Capacitive micromachined ultrasonic transducers (CMUTs) represent an effective alternative to piezoelectric transducers for medical ultrasound imaging applications. They are microelectromechanical devices fabricated using silicon micromachining techniques, developed in the last two decades in many laboratories. The interest for this novel transducer technology relies on its full compatibility with standard integrated circuit technology that makes it possible to integrate on the same chip the transducers and the electronics, thus enabling the realization of extremely low-cost and high-performance devices, including both 1-D or 2-D arrays. Being capacitive transducers, CMUTs require a high bias voltage to be properly operated in pulse-echo imaging applications. The typical bias supply residual ripple of high-quality high-voltage (HV) generators is in the millivolt range, which is comparable with the amplitude of the received echo signals, and it is particularly difficult to minimize. The aim of this paper is to analyze the classical CMUT biasing circuits, highlighting the features of each one, and to propose two novel HV generator architectures optimized for CMUT biasing applications. The first circuit proposed is an ultralow-residual ripple (generator that uses an extremely stable sinusoidal power oscillator topology. The second circuit employs a commercially available integrated step-up converter characterized by a particularly efficient switching topology. The circuit is used to bias the CMUT by charging a buffer capacitor synchronously with the pulsing sequence, thus reducing the impact of the switching noise on the received echo signals. The small area of the circuit (about 1.5 cm 2 ) makes it possible to generate the bias voltage inside the probe, very close to the CMUT, making the proposed solution attractive for portable applications. Measurements and experiments are shown to demonstrate the effectiveness of the new approaches presented.