These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Codon Usage Domains over Bacterial  

Microsoft Academic Search

The geography of codon bias distributions over prokaryotic genomes and its impact upon chromosomal organization are analyzed. To this aim, we introduce a clustering method based on information theory, specifically designed to cluster genes according to their codon usage and apply it to the coding sequences of Escherichia coli and Bacillus subtilis. One of the clusters identified in each of

Antoine Danchin; Mudassar Iqbal; Matteo Marsili; Massimo Vergassola

2

Divergence in codon usage of Lactobacillus species.  

PubMed Central

We have analyzed codon usage patterns of 70 sequenced genes from different Lactobacillus species. Codon usage in lactobacilli is highly biased. Both inter-species and intra-species heterogeneity of codon usage bias was observed. Codon usage in L. acidophilus is similar to that in L. helveticus, but dissimilar to that in L. bulgaricus, L. casei, L. pentosus and L. plantarum. Codon usage in the latter three organisms is not significantly different, but is different from that in L. bulgaricus. Inter-species differences in codon usage can, at least in part, be explained by differences in mutational drift. L. bulgaricus shows GC drift, whereas all other species show AT drift. L. acidophilus and L. helveticus rarely use NNG in family-box (a set of synonymous) codons, in contrast to all other species. This result may be explained by assuming that L. acidophilus and L. helveticus, but not other species examined, use a single tRNA species for translation of family-box codons. Differences in expression level of genes are positively correlated with codon usage bias. Highly expressed genes show highly biased codon usage, whereas weakly expressed genes show much less biased codon usage. Codon usage patterns at the 5'-end of Lactobacillus genes is not significantly different from that of entire genes. The GC content of codons 2-6 is significantly reduced compared with that of the remainder of the gene. The possible implications of a reduced GC content for the control of translation efficiency are discussed. PMID:8152923

Pouwels, P H; Leunissen, J A

1994-01-01

3

Rapid divergence of codon usage patterns within the rice genome  

PubMed Central

Background Synonymous codon usage varies widely between genomes, and also between genes within genomes. Although there is now a large body of data on variations in codon usage, it is still not clear if the observed patterns reflect the effects of positive Darwinian selection acting at the level of translational efficiency or whether these patterns are due simply to the effects of mutational bias. In this study, we have included both intra-genomic and inter-genomic comparisons of codon usage. This allows us to distinguish more efficiently between the effects of nucleotide bias and translational selection. Results We show that there is an extreme degree of heterogeneity in codon usage patterns within the rice genome, and that this heterogeneity is highly correlated with differences in nucleotide content (particularly GC content) between the genes. In contrast to the situation observed within the rice genome, Arabidopsis genes show relatively little variation in both codon usage and nucleotide content. By exploiting a combination of intra-genomic and inter-genomic comparisons, we provide evidence that the differences in codon usage among the rice genes reflect a relatively rapid evolutionary increase in the GC content of some rice genes. We also noted that the degree of codon bias was negatively correlated with gene length. Conclusion Our results show that mutational bias can cause a dramatic evolutionary divergence in codon usage patterns within a period of approximately two hundred million years. The heterogeneity of codon usage patterns within the rice genome can be explained by a balance between genome-wide mutational biases and negative selection against these biased mutations. The strength of the negative selection is proportional to the length of the coding sequences. Our results indicate that the large variations in synonymous codon usage are not related to selection acting on the translational efficiency of synonymous codons. PMID:17288579

Wang, Huai-Chun; Hickey, Donal A

2007-01-01

4

Quantifying Position-Dependent Codon Usage Bias  

PubMed Central

Although the mapping of codon to amino acid is conserved across nearly all species, the frequency at which synonymous codons are used varies both between organisms and between genes from the same organism. This variation affects diverse cellular processes including protein expression, regulation, and folding. Here, we mathematically model an additional layer of complexity and show that individual codon usage biases follow a position-dependent exponential decay model with unique parameter fits for each codon. We use this methodology to perform an in-depth analysis on codon usage bias in the model organism Escherichia coli. Our methodology shows that lowly and highly expressed genes are more similar in their codon usage patterns in the 5?-gene regions, but that these preferences diverge at distal sites resulting in greater positional dependency (pD, which we mathematically define later) for highly expressed genes. We show that position-dependent codon usage bias is partially explained by the structural requirements of mRNAs that results in increased usage of A/T rich codons shortly after the gene start. However, we also show that the pD of 4- and 6-fold degenerate codons is partially related to the gene copy number of cognate-tRNAs supporting existing hypotheses that posit benefits to a region of slow translation in the beginning of coding sequences. Lastly, we demonstrate that viewing codon usage bias through a position-dependent framework has practical utility by improving accuracy of gene expression prediction when incorporating positional dependencies into the Codon Adaptation Index model. PMID:24710515

Hockenberry, Adam J.; Sirer, M. Irmak; Amaral, Luis A. Nunes; Jewett, Michael C.

2014-01-01

5

Codon Usage Domains over Bacterial Chromosomes  

E-print Network

to their codon usage and apply it to the coding sequences of Escherichia coli and Bacillus subtilis. One between bias and tRNA abundance was early remarked both in Escherichia coli and Saccharomyces cerevisiae in ribosomal proteins and some additional genes, highly expressed under exponential growth conditions [5

Kent, University of

6

An evolutionary perspective on synonymous codon usage in unicellular organisms  

Microsoft Academic Search

Summary Observed patterns of synonymous codon usage are explained in terms of the joint effects of mutation, selection, and random drift. Examination of the codon usage in 165Escherichia coli genes reveals a consistent trend of increasing bias with increasing gene expression level. Selection on codon usage appears to be unidirectional, so that the pattern seen in lowly expressed genes is

Paul M. Sharp; Wen-Hsiung Li

1986-01-01

7

The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications.  

PubMed Central

A simple, effective measure of synonymous codon usage bias, the Codon Adaptation Index, is detailed. The index uses a reference set of highly expressed genes from a species to assess the relative merits of each codon, and a score for a gene is calculated from the frequency of use of all codons in that gene. The index assesses the extent to which selection has been effective in moulding the pattern of codon usage. In that respect it is useful for predicting the level of expression of a gene, for assessing the adaptation of viral genes to their hosts, and for making comparisons of codon usage in different organisms. The index may also give an approximate indication of the likely success of heterologous gene expression. PMID:3547335

Sharp, P M; Li, W H

1987-01-01

8

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

NASA Astrophysics Data System (ADS)

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

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

2011-10-01

9

Causes and Implications of Codon Usage Bias in RNA Viruses  

PubMed Central

Choice of synonymous codons depends on nucleotide/dinucleotide composition of the genome (termed mutational pressure) and relative abundance of tRNAs in a cell (translational pressure). Mutational pressure is commonly simplified to genomic GC content; however mononucleotide and dinucleotide frequencies in different genomes or mRNAs may vary significantly, especially in RNA viruses. A series of in silico shuffling algorithms were developed to account for these features and analyze the relative impact of mutational pressure components on codon usage bias in RNA viruses. Total GC content was a poor descriptor of viral genome composition and causes of codon usage bias. Genomic nucleotide content was the single most important factor of synonymous codon usage. Moreover, the choice between compatible amino acids (e.g., leucine and isoleucine) was strongly affected by genomic nucleotide composition. Dinucleotide composition at codon positions 2-3 had additional effect on codon usage. Together with mononucleotide composition bias, it could explain almost the entire codon usage bias in RNA viruses. On the other hand, strong dinucleotide content bias at codon position 3-1 found in some viruses had very little effect on codon usage. A hypothetical innate immunity sensor for CpG in RNA could partially explain the codon usage bias, but due to dependence of virus translation upon biased host translation machinery, experimental studies are required to further explore the source of dinucleotide bias in RNA viruses. PMID:23451064

Belalov, Ilya S.; Lukashev, Alexander N.

2013-01-01

10

Complex Codon Usage Pattern and Compositional Features of Retroviruses  

PubMed Central

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. PMID:24288576

RoyChoudhury, Sourav; Mukherjee, Debaprasad

2013-01-01

11

Comprehensive analysis of the overall codon usage patterns in equine infectious anemia virus  

PubMed Central

Background Equine infectious anemia virus (EIAV) is an important animal model for understanding the relationship between viral persistence and the host immune response during lentiviral infections. Comparison and analysis of the codon usage model between EIAV and its hosts is important for the comprehension of viral evolution. In our study, the codon usage pattern of EIAV was analyzed from the available 29 full-length EIAV genomes through multivariate statistical methods. Finding Effective number of codons (ENC) suggests that the codon usage among EIAV strains is slightly biased. The ENC-plot analysis demonstrates that mutation pressure plays a substantial role in the codon usage pattern of EIAV, whereas other factors such as geographic distribution and host translation selection also take part in the process of EIAV evolution. Comparative analysis of codon adaptation index (CAI) values among EIAV and its hosts suggests that EIAV utilize the translational resources of horse more efficiently than that of donkey. Conclusion The codon usage bias in EIAV is slight and mutation pressure is the main factor that affects codon usage variation in EIAV. These results suggest that EIAV genomic biases are the result of the co-evolution of genome composition and the ability to evade the host’s immune response. PMID:24359511

2013-01-01

12

Measure of synonymous codon usage diversity among genes in bacteria  

PubMed Central

Background In many bacteria, intragenomic diversity in synonymous codon usage among genes has been reported. However, no quantitative attempt has been made to compare the diversity levels among different genomes. Here, we introduce a mean dissimilarity-based index (Dmean) for quantifying the level of diversity in synonymous codon usage among all genes within a genome. Results The application of Dmean to 268 bacterial genomes shows that in bacteria with extremely biased genomic G+C compositions there is little diversity in synonymous codon usage among genes. Furthermore, our findings contradict previous reports. For example, a low level of diversity in codon usage among genes has been reported for Helicobacter pylori, but based on Dmean, the diversity level of this species is higher than those of more than half of bacteria tested here. The discrepancies between our findings and previous reports are probably due to differences in the methods used for measuring codon usage diversity. Conclusion We recommend that Dmean be used to measure the diversity level of codon usage among genes. This measure can be applied to other compositional features such as amino acid usage and dinucleotide relative abundance as a genomic signature. PMID:19480720

Suzuki, Haruo; Saito, Rintaro; Tomita, Masaru

2009-01-01

13

Evidence that Natural Selection on Codon Usage in Drosophila pseudoobscura Varies Across Codons  

PubMed Central

Like other species of Drosophila, Drosophila pseudoobscura has a distinct bias toward the usage of C- and G-ending codons. Previous studies have indicated that this bias is due, at least in part, to natural selection. Codon bias clearly differs among amino acids (and other codon classes) in Drosophila, which may reflect differences in the intensity of selection on codon usage. Ongoing natural selection on synonymous codon usage should be reflected in the shapes of the site frequency spectra of derived states at polymorphic positions. Specifically, regardless of other demographic effects on the spectrum, it should be shifted toward higher values for changes from less-preferred to more-preferred codons, and toward lower values for the converse. If the intensity of natural selection is increased, shifts in the site frequency spectra should be more pronounced. A total of 33,729 synonymous polymorphic sites on Chromosome 2 in D. pseudoobscura were analyzed. Shifts in the site frequency spectra are consistent with differential intensity of natural selection on codon usage, with stronger shifts associated with higher codon bias. The shifts, in general, are greater for polymorphic synonymous sites than for polymorphic intron sites, also consistent with natural selection. However, unlike observations in D. melanogaster, codon bias is not reduced in areas of low recombination in D. pseudoobscura; the site frequency spectrum signal for selection on codon usage remains strong in these regions. However, diversity is reduced, as expected. It is possible that estimates of low recombination reflect a recent change in recombination rate. PMID:24531731

Kliman, Richard M.

2014-01-01

14

The Effect of Multiple Evolutionary Selections on Synonymous Codon Usage of Genes in the Mycoplasma bovis Genome  

PubMed Central

Mycoplasma bovis is a major pathogen causing arthritis, respiratory disease and mastitis in cattle. A better understanding of its genetic features and evolution might represent evidences of surviving host environments. In this study, multiple factors influencing synonymous codon usage patterns in M. bovis (three strains’ genomes) were analyzed. The overall nucleotide content of genes in the M. bovis genome is AT-rich. Although the G and C contents at the third codon position of genes in the leading strand differ from those in the lagging strand (p<0.05), the 59 synonymous codon usage patterns of genes in the leading strand are highly similar to those in the lagging strand. The over-represented codons and the under-represented codons were identified. A comparison of the synonymous codon usage pattern of M. bovis and cattle (susceptible host) indicated the independent formation of synonymous codon usage of M. bovis. Principal component analysis revealed that (i) strand-specific mutational bias fails to affect the synonymous codon usage pattern in the leading and lagging strands, (ii) mutation pressure from nucleotide content plays a role in shaping the overall codon usage, and (iii) the major trend of synonymous codon usage has a significant correlation with the gene expression level that is estimated by the codon adaptation index. The plot of the effective number of codons against the G+C content at the third codon position also reveals that mutation pressure undoubtedly contributes to the synonymous codon usage pattern of M. bovis. Additionally, the formation of the overall codon usage is determined by certain evolutionary selections for gene function classification (30S protein, 50S protein, transposase, membrane protein, and lipoprotein) and translation elongation region of genes in M. bovis. The information could be helpful in further investigations of evolutionary mechanisms of the Mycoplasma family and heterologous expression of its functionally important proteins. PMID:25350396

Zhou, Jian-hua; Ding, Yao-zhong; He, Ying; Chu, Yue-feng; Zhao, Ping; Ma, Li-ya; Wang, Xin-jun; Li, Xue-rui; Liu, Yong-sheng

2014-01-01

15

CodonExplorer: An Interactive Online Database for the Analysis of Codon Usage and Sequence Composition  

PubMed Central

The analysis of DNA composition and codon usage reveals many factors that influence the evolution of genes and genomes. In this chapter, we show how to use CodonExplorer, a web tool and interactive database that contains millions of genes, to better understand the principles governing evolution at the single gene and whole-genome level. We present principles and practical procedures for using analyses of GC content and codon usage frequency to identify highly expressed or horizontally transferred genes and to study the relative contribution of different types of mutation to gene and genome composition. CodonExplorer’s combination of a user-friendly web interface and a comprehensive genomic database makes these diverse analyses fast and straightforward to perform. CodonExplorer is thus a powerful tool that facilitates and automates a wide range of compositional analyses. PMID:19378146

Zaneveld, Jesse; Hamady, Micah; Sueoka, Noboru; Knight, Rob

2010-01-01

16

INCA: synonymous codon usage analysis and clustering by means of self-organizing map  

Microsoft Academic Search

Summary: INteractive Codon usage Analysis (INCA) provides an array of features useful in analysis of synonymous codon usage in whole genomes. In addition to computing codon fre- quencies and several usage indices, such as 'codon bias', effective Nc and CAI, the primary strength of INCA has numer- ous options for the interactive graphical display of calculated values, thus allowing visual

Fran Supek; Kristian Vlahovicek

2004-01-01

17

Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes  

Microsoft Academic Search

BACKGROUND: Codon usage bias has been widely reported to correlate with GC composition. However, the quantitative relationship between codon usage bias and GC composition across species has not been reported. RESULTS: Based on an informatics method (SCUO) we developed previously using Shannon informational theory and maximum entropy theory, we investigated the quantitative relationship between codon usage bias and GC composition.

Xiu-Feng Wan; Dong Xu; Andris Kleinhofs; Jizhong Zhou

2004-01-01

18

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus.  

PubMed

Adaptation in the overall codon usage pattern of West Nile virus (WNV) to that of two hosts was estimated based on the synonymous codon usage value (RSCU). Synonymous codon usage biases for the beginning coding sequence of this virus were also analyzed by calculating the usage fluctuation for each synonymous codon along the target region (the first 270 codon sites of the whole coding sequence of WNV). Adaptation of WNV to Anopheles gambiae regarding the overall codon usage revealed a mixture of synonymous codon usage patterns between this virus and its vector. Regarding the adaptation of WNV to its dead-end host and codon usage, although a mixture of overall codon usage patterns exists, the number of codons with reversed tendency codon usage is lower than that between the virus and its vector. In addition, some codons with low RSCU values for this virus are highly selected in the beginning translation region of WNV, while codons with low RSCU values in this region tend to pair with tRNAs present in low abundance in the host, suggesting that highly selected codons in a specific region in the beginning region of WNV are, to some degree, influenced by the corresponding low tRNA abundance of hosts to regulate the translation speed of the WNV polyprotein. PMID:25222233

Ma, X X; Feng, Y P; Liu, J L; Chen, L; Zhao, Y Q; Guo, P H; Guo, J Z; Ma, L Y; Ma, Z R

2014-01-01

19

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

PubMed Central

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. PMID:22435713

2012-01-01

20

RCDI/eRCDI: a web-server to estimate codon usage deoptimization  

PubMed Central

Background The Relative Codon Deoptimization Index (RCDI) was developed by Mueller et al. (2006) as measure of codon deoptimization by comparing how similar is the codon usage of a gene and the codon usage of a reference genome. Findings RCDI/eRCDI is a web application server that calculates the Relative Codon Deoptimization Index and a new expected value for the RCDI (eRCDI). The RCDI is used to estimate the similarity of the codon frequencies of a specific gene in comparison to a given reference genome. The eRCDI is determined by generating random sequences with similar G+C and amino acid composition to the input sequences and may be used as an indicator of the significance of the RCDI values. RCDI/eRCDI is freely available at http://genomes.urv.cat/CAIcal/RCDI. Conclusions This web server will be a useful tool for genome analysis, to understand host-virus phylogenetic relationships or to infer the potential host range of a virus and its replication strategy, as well as in experimental virology to ease the step of gene design for heterologous protein expression. PMID:20356391

2010-01-01

21

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

PubMed Central

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

Tong, Yigang

2014-01-01

22

Gene expression level influences amino acid usage, but not codon usage, in the tsetse fly endosymbiont Wigglesworthia  

Microsoft Academic Search

Wigglesworthia glossinidia brevipalpis, the obligate bacterial endosymbiont of the tsetse fly Glossinabrevipalpis,ischaracterizedbyextremegenomereductionandATnucleotidecomposition bias. Here, multivariate statistical analyses are used to test the hypothesis that mutational bias and genetic drift shape synonymous codon usage and amino acid usage of Wigglesworthia. The results show that synonymous codon usage patterns vary little across the genome and do not distinguish genes of putative high

J. T. Herbeck

2003-01-01

23

Codon usage bias, tRNA modifications and translational selection in bacteria  

Microsoft Academic Search

In this thesis, codon usage bias is studied in a large number of bacterial genomes. The codon frequency of each codon is measured as a fraction of the total number of codons for each amino acid, which can be used to calculate the potential selection strength in a genome according to the population genetics theory of selection, mutation and drift.

Wenqi Ran

2010-01-01

24

Selection pressures on codon usage in the complete genome of bacteriophage T7  

Microsoft Academic Search

Summary We searched the complete 39,936 base DNA sequence of bacteriophage T7 for nonrandomness that might be attributed to natural selection. Codon usage in the 50 genes of T7 is nonrandom, both over the whole code and among groups of synonymous codons. There is a great excess of purineany base-pyrimidine (RNY) codons. Codon usage varies between genes, but from the

Paul M. Sharp; Mark S. Rogers; David J. McConnell

1985-01-01

25

A PECULIAR CODON USAGE PATTERN REVEALED AFTER REMOVING THE EFFECT OF DNA METHYLATION  

Microsoft Academic Search

Summary DNA methylation and deamination increases the C?T mutation rate in CpG dinucleotides, especially in vertebrate genomes. This has profound effect on codon usage in heavily vertebrate genomes, and may obscure the effect of other factors on codon usage bias. We have classified the sense codons into three groups: those decreased by DNA methylation (i.e., CpG-containing codons), those increased by

Xuhua Xia

26

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

PubMed Central

Background Codon usage analysis has been a classical topic for decades and has significances for studies of evolution, mRNA translation, and new gene discovery, etc. While the codon usage varies among different members of the plant kingdom, indicating the necessity for species-specific study, this work has mostly been limited to model organisms. Recently, the development of deep sequencing, especial RNA-Seq, has made it possible to carry out studies in non-model species. Result RNA-Seq data of Chinese bayberry was analyzed to investigate the bias of codon usage and codon pairs. High frequency codons (AGG, GCU, AAG and GAU), as well as low frequency ones (NCG and NUA codons) were identified, and 397 high frequency codon pairs were observed. Meanwhile, 26 preferred and 141 avoided neighboring codon pairs were also identified, which showed more significant bias than the same pairs with one or more intervening codons. Codon patterns were also analyzed at the plant kingdom, organism and gene levels. Changes during plant evolution were evident using RSCU (relative synonymous codon usage), which was even more significant than GC3s (GC content of 3rd synonymous codons). Nine GO categories were differentially and independently influenced by CAI (codon adaptation index) or GC3s, especially in 'Molecular function’ category. Within a gene, the average CAI increased from 0.720 to 0.785 in the first 50 codons, and then more slowly thereafter. Furthermore, the preferred as well as avoided codons at the position just following the start codon AUG were identified and discussed in relation to the key positions in Kozak sequences. Conclusion A comprehensive codon usage Table and number of high-frequency codon pairs were established. Bias in codon usage as well as in neighboring codon pairs was observed, and the significance of this in avoiding DNA mutation, increasing protein production and regulating protein synthesis rate was proposed. Codon usage patterns at three levels were revealed and the significance in plant evolution analysis, gene function classification, and protein translation start site predication were discussed. This work promotes the study of codon biology, and provides some reference for analysis and comprehensive application of RNA-Seq data from other non-model species. PMID:24160180

2013-01-01

27

Synonymous Codon Usage in Drosophila melanogaster: Natural Selection and Translational Accuracy  

Microsoft Academic Search

I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency

Hiroshi Akashi

1994-01-01

28

The Evolution of Biased Codon and Amino Acid Usage in Nematode Genomes Asher D. Cutter,1  

E-print Network

codon-usage trends defined by base compositional properties of individual nematode genomes. Introduction,orskewedlevelsofpolymor- phism at synonymous sites (Bennetzen and Hall 1982; Sharp and Li 1987; Akashi 1995; Duret and Mouchiroud, genomes exhibiting the strongest biases in codon usage cor- respond to species of bacteria and yeast

Cutter, Asher D.

29

Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis  

PubMed Central

We measured the expression pattern and analyzed codon usage in 8,133, 1,550, and 2,917 genes, respectively, from Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. In those three species, we observed a clear correlation between codon usage and gene expression levels and showed that this correlation is not due to a mutational bias. This provides direct evidence for selection on silent sites in those three distantly related multicellular eukaryotes. Surprisingly, there is a strong negative correlation between codon usage and protein length. This effect is not due to a smaller size of highly expressed proteins. Thus, for a same-expression pattern, the selective pressure on codon usage appears to be lower in genes encoding long rather than short proteins. This puzzling observation is not predicted by any of the current models of selection on codon usage and thus raises the question of how translation efficiency affects fitness in multicellular organisms. PMID:10200288

Duret, Laurent; Mouchiroud, Dominique

1999-01-01

30

Mapping codon usage of the translation initiation region in porcine reproductive and respiratory syndrome virus genome  

PubMed Central

Background Porcine reproductive and respitatory syndrome virus (PRRSV) is a recently emerged pathogen and severely affects swine populations worldwide. The replication of PRRSV is tightly controlled by viral gene expression and the codon usage of translation initiation region within each gene could potentially regulate the translation rate. Therefore, a better understanding of the codon usage pattern of the initiation translation region would shed light on the regulation of PRRSV gene expression. Results In this study, the codon usage in the translation initiation region and in the whole coding sequence was compared in PRRSV ORF1a and ORFs2-7. To investigate the potential role of codon usage in affecting the translation initiation rate, we established a codon usage model for PRRSV translation initiation region. We observed that some non-preferential codons are preferentially used in the translation initiation region in particular ORFs. Although some positions vary with codons, they intend to use codons with negative CUB. Furthermore, our model of codon usage showed that the conserved pattern of CUB is not directly consensus with the conserved sequence, but shaped under the translation selection. Conclusions The non-variation pattern with negative CUB in the PRRSV translation initiation region scanned by ribosomes is considered the rate-limiting step in the translation process. PMID:22014033

2011-01-01

31

Translational effects of differential codon usage among intragenic domains of new genes in Drosophila.  

PubMed

Evolved codon usages often pose a technical challenge over the expressing of eukaryotic genes in microbial systems because of changed translational machinery. In the present study, we investigated the translational effects of intragenic differential codon usage on the expression of the new Drosophila gene, jingwei (jgw), a chimera derived from two unrelated parental genes: Ymp and Adh. We found that jgw possesses a strong intragenic differential usage of synonymous codons, i.e. the Adh-derived C-domain has a significantly higher codon bias than that of the Ymp-derived N-domain (P=0.0023 by t-test). Additional evolutionary analysis revealed the heterogeneous distribution of rare codons, implicating its role in gene regulation and protein translation. The in vitro expression of jgw further demonstrated that the heterogeneous distribution of rare codons has played a role in regulating gene expression, particularly, affecting the quality of protein translation. PMID:15833448

Zhang, Jianming; Long, Manyuan; Li, Liming

2005-05-01

32

Comprehensive analysis of stop codon usage in bacteria and its correlation with release factor abundance.  

PubMed

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

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

2014-10-31

33

Differential Selective Constraints Shaping Codon Usage Pattern of Housekeeping and Tissue-specific Homologous Genes of Rice and Arabidopsis  

PubMed Central

Intra-genomic variation between housekeeping and tissue-specific genes has always been a study of interest in higher eukaryotes. To-date, however, no such investigation has been done in plants. Availability of whole genome expression data for both rice and Arabidopsis has made it possible to examine the evolutionary forces in shaping codon usage pattern in both housekeeping and tissue-specific genes in plants. In the present work, we have taken 4065 rice–Arabidopsis homologous gene pairs to study evolutionary forces responsible for codon usage divergence between housekeeping and tissue-specific genes. In both rice and Arabidopsis, it is mutational bias that regulates error minimization in highly expressed genes of both housekeeping and tissue-specific genes. Our results show that, in comparison to tissue-specific genes, housekeeping genes are under strong selective constraint in plants. However, in tissue-specific genes, lowly expressed genes are under stronger selective constraint compared with highly expressed genes. We demonstrated that constraint acting on mRNA secondary structure is responsible for modulating codon usage variations in rice tissue-specific genes. Thus, different evolutionary forces must underline the evolution of synonymous codon usage of highly expressed genes of housekeeping and tissue-specific genes in rice and Arabidopsis. PMID:18827062

Mukhopadhyay, Pamela; Basak, Surajit; Ghosh, Tapash Chandra

2008-01-01

34

Constraint on di-nucleotides by codon usage bias in bacterial genomes.  

PubMed

It has been reported earlier that the relative di-nucleotide frequency (RDF) in different parts of a genome is similar while the frequency is variable among different genomes. So RDF is termed as genome signature in bacteria. It is not known if the constancy in RDF is governed by genome wide mutational bias or by selection. Here we did comparative analysis of RDF between the inter-genic and the coding sequences in seventeen bacterial genomes, whose gene expression data was available. The constraint on di-nucleotides was found to be higher in the coding sequences than that in the inter-genic regions and the constraint at the 2nd codon position was more than that in the 3rd position within a genome. Further analysis revealed that the constraint on di-nucleotides at the 2nd codon position is greater in the high expression genes (HEG) than that in the whole genomes as well as in the low expression genes (LEG). We analyzed RDF at the 2nd and the 3rd codon positions in simulated coding sequences that were computationally generated by keeping the codon usage bias (CUB) according to genome G+C composition and the sequence of amino acids unaltered. In the simulated coding sequences, the constraint observed was significantly low and no significant difference was observed between the HEG and the LEG in terms of di-nucleotide constraint. This indicated that the greater constraint on di-nucleotides in the HEG was due to the stronger selection on CUB in these genes in comparison to the LEG within a genome. Further, we did comparative analyses of the RDF in the HEG rpoB and rpoC of 199 bacteria, which revealed a common pattern of constraints on di-nucleotides at the 2nd codon position across these bacteria. To validate the role of CUB on di-nucleotide constraint, we analyzed RDF at the 2nd and the 3rd codon positions in simulated rpoB/rpoC sequences. The analysis revealed that selection on CUB is an important attribute for the constraint on di-nucleotides at these positions in bacterial genomes. We believe that this study has come with major findings of the role of CUB on di-nucleotide constraint in bacterial genomes. PMID:24333347

Satapathy, Siddhartha Sankar; Powdel, Bhes Raj; Dutta, Malay; Buragohain, Alak Kumar; Ray, Suvendra Kumar

2014-02-15

35

Mutational and Selective Pressures on Codon and Amino Acid Usage in Buchnera, Endosymbiotic Bacteria of Aphids  

Microsoft Academic Search

We have explored compositional variation at synonymous (codon usage) and nonsynonymous (amino acid usage) positions in three complete genomes of Buchnera, endosymbiotic bacteria of aphids, and also in their orthologs in Escherichia coli, a close free-living relative. We sought to discriminate genes of variable expression levels in order to weigh the relative contributions of mutational bias and selection in the

Claude Rispe; Francois Delmotte; Roeland C. H. J. van Ham; Andres Moya

2003-01-01

36

Mutational and selective pressures on codon and amino acid usage in Buchnera, endosymbiotic bacteria of aphids  

Microsoft Academic Search

We have explored compositional variation at synonymous (codon usage) and nonsynonymous (amino acid usage) positions in three complete genomes of Buchnera, endosymbiotic bacteria of aphids, and also in their orthologs in Escherichia coli, a close free-living relative. We sought to discriminate genes of variable expression levels in order to weigh the relative contributions of mutational bias and selection in the

C. Rispe; F. Delmotte; Ham van R. C. H. J; A. Moya

2004-01-01

37

Enhanced Production of Recombinant Mycobacterium tuberculosis Antigens in Escherichia coli by Replacement of Low-Usage Codons  

Microsoft Academic Search

A major obstacle to development of subunit vaccines and diagnostic reagents for tuberculosis is the inability to produce large quantities of these proteins. To test the hypothesis that poor expression of some mycobacterial genes in Escherichia coli is due, in part, to the presence of low-usage E. coli codons, we used site-directed mutagenesis to convert low-usage codons to high-usage codons

DAVID L. LAKEY; RAMA K. R. VOLADRI; KATHRYN M. EDWARDS; CYNTHIA HAGER; BUKA SAMTEN; ROBERT S. WALLIS; PETER F. BARNES; DOUGLAS S. KERNODLE

2000-01-01

38

Genome-wide selection on codon usage at the population level in the fungal model organism Neurospora crassa.  

PubMed

Many organisms exhibit biased codon usage in their genome, including the fungal model organism Neurospora crassa. The preferential use of subset of synonymous codons (optimal codons) at the macroevolutionary level is believed to result from a history of selection to promote translational efficiency. At present, few data are available about selection on optimal codons at the microevolutionary scale, that is, at the population level. Herein, we conducted a large-scale assessment of codon mutations at biallelic sites, spanning more than 5,100 genes, in 2 distinct populations of N. crassa: the Caribbean and Louisiana populations. Based on analysis of the frequency spectra of synonymous codon mutations at biallelic sites, we found that derived (nonancestral) optimal codon mutations segregate at a higher frequency than derived nonoptimal codon mutations in each population; this is consistent with natural selection favoring optimal codons. We also report that optimal codon variants were less frequent in longer genes and that the fixation of optimal codons was reduced in rapidly evolving long genes/proteins, trends suggestive of genetic hitchhiking (Hill-Robertson) altering codon usage variation. Notably, nonsynonymous codon mutations segregated at a lower frequency than synonymous nonoptimal codon mutations (which impair translational efficiency) in each N. crassa population, suggesting that changes in protein composition are more detrimental to fitness than mutations altering translation. Overall, the present data demonstrate that selection, and partly genetic interference, shapes codon variation across the genome in N. crassa populations. PMID:22334579

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

2012-08-01

39

Codon usage suggests that translational selection has a major impact on protein expression in trypanosomatids  

PubMed Central

Background Different proteins are required in widely different quantities to build a living cell. In most organisms, transcription control makes a major contribution to differential expression. This is not the case in trypanosomatids where most genes are transcribed at an equivalent rate within large polycistronic clusters. Thus, trypanosomatids must use post-transcriptional control mechanisms to balance gene expression requirements. Results Here, the evidence for translational selection, the enrichment of 'favoured' codons in more highly expressed genes, is explored. A set of highly expressed, tandem-repeated genes display codon bias in Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. The tRNA complement reveals forty-five of the sixty-one possible anticodons indicating widespread use of 'wobble' tRNAs. Consistent with translational selection, cognate tRNA genes for favoured codons are over-represented. Importantly, codon usage (Codon Adaptation Index) correlates with predicted and observed expression level. In addition, relative codon bias is broadly conserved among syntenic genes from different trypanosomatids. Conclusion Synonymous codon bias is correlated with tRNA gene copy number and with protein expression level in trypanosomatids. Taken together, the results suggest that translational selection is the dominant mechanism underlying the control of differential protein expression in these organisms. The findings reveal how trypanosomatids may compensate for a paucity of canonical Pol II promoters and subsequent widespread constitutive RNA polymerase II transcription. PMID:18173843

Horn, David

2008-01-01

40

An Example in Kleisli: Codon Usage Extraction Made Easy Jiren Wang and Limsoon Wong  

E-print Network

Asked Questions'' category: The extraction and assembly of exons from large DNA sequence databasesAn Example in Kleisli: Codon Usage Extraction Made Easy Jiren Wang and Limsoon Wong Bio in this paper. First, we wanted to build a system that could extract coding sequences of a specified organism

Wong, Limsoon

41

Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome  

PubMed Central

We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest. PMID:19131380

Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

2009-01-01

42

Environmental shaping of codon usage and functional adaptation across microbial communities  

PubMed Central

Microbial communities represent the largest portion of the Earth’s biomass. Metagenomics projects use high-throughput sequencing to survey these communities and shed light on genetic capabilities that enable microbes to inhabit every corner of the biosphere. Metagenome studies are generally based on (i) classifying and ranking functions of identified genes; and (ii) estimating the phyletic distribution of constituent microbial species. To understand microbial communities at the systems level, it is necessary to extend these studies beyond the species’ boundaries and capture higher levels of metabolic complexity. We evaluated 11 metagenome samples and demonstrated that microbes inhabiting the same ecological niche share common preferences for synonymous codons, regardless of their phylogeny. By exploring concepts of translational optimization through codon usage adaptation, we demonstrated that community-wide bias in codon usage can be used as a prediction tool for lifestyle-specific genes across the entire microbial community, effectively considering microbial communities as meta-genomes. These findings set up a ‘functional metagenomics’ platform for the identification of genes relevant for adaptations of entire microbial communities to environments. Our results provide valuable arguments in defining the concept of microbial species through the context of their interactions within the community. PMID:23921637

Roller, Masa; Lucic, Vedran; Nagy, Istvan; Perica, Tina; Vlahovicek, Kristian

2013-01-01

43

Large-scale genomic analysis of codon usage in dengue virus and evaluation of its phylogenetic dependence.  

PubMed

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

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

2014-01-01

44

Evolution of the vesicular stomatitis viruses: Divergence and codon usage bias.  

PubMed

Four Vesiculovirus species causing vesicular stomatitis in the Americas, together with two closely related insect isolates, can be phyletically classified into two major groups: New Jersey (NJ) and Indiana (IN). Here, Bayesian coalescent analyses were conducted to the time-stamped entire coding sequences of the G gene of these vesiculoviruses, with emphasis on their divergence scenario. The primary bifurcation was a much ancient event that might have taken place around 1.8 million years ago between NJ and IN, which shared a similar high mean rate. Interestingly, the overall codon usage bias pattern of these viruses resembled that of the insect vectors rather than the livestock hosts. PMID:25172582

Liang, Yang; He, Mei; Teng, Chun-Bo

2014-11-01

45

Analysis of the Relationship between Genomic GC Content and Patterns of Base Usage, Codon Usage and Amino Acid Usage in Prokaryotes: Similar GC Content Adopts Similar Compositional Frequencies Regardless of the Phylogenetic Lineages  

PubMed Central

The GC contents of 2670 prokaryotic genomes that belong to diverse phylogenetic lineages were analyzed in this paper. These genomes had GC contents that ranged from 13.5% to 74.9%. We analyzed the distance of base frequencies at the three codon positions, codon frequencies, and amino acid compositions across genomes with respect to the differences in the GC content of these prokaryotic species. We found that although the phylogenetic lineages were remote among some species, a similar genomic GC content forced them to adopt similar base usage patterns at the three codon positions, codon usage patterns, and amino acid usage patterns. Our work demonstrates that in prokaryotic genomes: a) base usage, codon usage, and amino acid usage change with GC content with a linear correlation; b) the distance of each usage has a linear correlation with the GC content difference; and c) GC content is more essential than phylogenetic lineage in determining base usage, codon usage, and amino acid usage. This work is exceptional in that we adopted intuitively graphic methods for all analyses, and we used these analyses to examine as many as 2670 prokaryotes. We hope that this work is helpful for understanding common features in the organization of microbial genomes. PMID:25255224

Zhang, Hui-Xiong; Guo, Feng-Biao

2014-01-01

46

General trends in selectively driven codon usage biases in the domain archaea.  

PubMed

Since the advent of rapid techniques for sequencing DNA in the mid 70's, it became clear that all codons coding for the same amino acid are not used according to neutral expectations. In the last 30 years, several theories were proposed for explaining this fact. However, the most important concepts were the result of analyses carried out in Bacteria, and unicellular and multicellular eukaryotes like mammals (in other words, in two of the three Domains of life). In this communication, we study the main forces that shape codon usage in Archaeae under an evolutionary perspective. This is important because, as known, the orthologous genes related with the informational system in this Domain (replication, transcription and translation) are more similar to eukaryotes than to Bacteria. Our results show that the effect of selection acting at the level of translation is present in the Domain but mainly restricted to only a phylum (Euryarchaeota) and therefore is not as extended as in Bacteria. Besides, we describe the phylogenetic distribution of translational optimal codons and estimate the effect of selection acting at the level of accuracy. Finally, we discuss these results under some peculiarities that characterize this Domain. PMID:25239794

Iriarte, Andrés; Jara, Eugenio; Leytón, Lucía; Diana, Leticia; Musto, Héctor

2014-10-01

47

Antagonistic relationships between intron content and codon usage bias of genes in three mosquito species: functional and evolutionary implications  

PubMed Central

Genome biology of mosquitoes holds potential in developing knowledge-based control strategies against vectorborne diseases such as malaria, dengue, West Nile, and others. Although the genomes of three major vector mosquitoes have been sequenced, attempts to elucidate the relationship between intron and codon usage bias across species in phylogenetic contexts are limited. In this study, we investigated the relationship between intron content and codon bias of orthologous genes among three vector mosquito species. We found an antagonistic relationship between codon usage bias and the intron number of genes in each mosquito species. The pattern is further evident among the intronless and the intron-containing orthologous genes associated with either low or high codon bias among the three species. Furthermore, the covariance between codon bias and intron number has a directional component associated with the species phylogeny when compared with other nonmosquito insects. By applying a maximum likelihood–based continuous regression method, we show that codon bias and intron content of genes vary among the insects in a phylogeny-dependent manner, but with no evidence of adaptive radiation or species-specific adaptation. We discuss the functional and evolutionary significance of antagonistic relationships between intron content and codon bias. PMID:24187589

Behura, Susanta K; Singh, Brajendra K; Severson, David W

2013-01-01

48

Residential energy usage comparison: Findings  

SciTech Connect

This report presents the research methods and results from the Residential Energy Usage Comparison (REUC) project, a joint effort by Southern California Edison Company (SCE) and the Electric Power Research Institute (EPRI). The REUC project design activities began in early 1986. The REUC project is an innovative demand-site project designed to measure and compare typical energy consumption patterns of energy efficient residential electric and gas appliances. 95 figs., 33 tabs.

Smith, B.A.; Uhlaner, R.T.; Cason, T.N.; Courteau, S. (Quantum Consulting, Inc., Berkeley, CA (United States))

1991-08-01

49

Production of ?-cyclodextrin glycosyltransferase in Bacillus megaterium MS941 by systematic codon usage optimization.  

PubMed

?-Cyclodextrin glycosyltransferase is a key enzyme in the cyclodextrin industry. The Gram-positive bacterium Bacillus megaterium was chosen for production of recombinant ?-CGTase for safety concerns. Successful production of heterologous ?-CGTase was achieved by adapting the original ?-cgt gene to the codon usage of B. megaterium by systematic codon optimization. This balanced the tRNA pool and reduced ribosomal traffic jams. Protein expression and secretion was ensured by using the strong inducible promoter P(xyl) and the signal peptide SP(LipA). The impact of culture medium composition and induction strategies on ?-CGTase production was systematically analyzed. Production and secretion at 32 °C for 24 h using modified culture medium was optimal for ?-CGTase yield. Batch- and simple fed-batch fermentation was applied to achieve a high yield of 48.9 U·mL(-1), which was the highest activity reported for a Bacillus species, making this production system a reasonable alternative to Escherichia coli. PMID:23013320

Zhou, Jingwen; Liu, Hua; Du, Guocheng; Li, Jianghua; Chen, Jian

2012-10-17

50

Papillomavirus Capsid Protein Expression Level Depends on the Match between Codon Usage and tRNA Availability  

PubMed Central

Translation of mRNA encoding the L1 and L2 capsid proteins of papillomavirus (PV) is restricted in vivo to differentiated epithelial cells, although transcription of the L1 and L2 late genes occurs more widely. The codon composition of PV late genes is quite different from that of most mammalian genes. To test the possibility that PV late gene codon composition determines the efficiency of PV late gene expression in some cell types, synthetic bovine papillomavirus type 1 (BPV1) late genes were constructed with codon composition modified to resemble the typical mammalian gene. Expression of these genes from a strong promoter in Cos-1 cells was compared with expression of wild-type BPV1 late genes from the same promoter. Both unmodified and modified PV late genes were transcribed in Cos-1 cells, but only the codon-modified genes were translated. In vitro translation of wild-type but not synthetic BPV1 L1 mRNA was markedly enhanced by addition of aminoacyl-tRNAs. Codon composition thus limits BPV1 late gene translation in Cos-1 cells, and this limitation can be overcome by modification of the codon composition of the genes or by provision of excess tRNA. Replacement of codons in the green fluorescent protein (gfp) gene with those frequently used in PV late genes did not alter gfp transcription in Cos-1 cells but almost abolished translation, supporting the hypothesis that the observed differences in efficiency of translation of modified and unmodified PV capsid genes were related to codon usage rather than mRNA structure. As tRNA populations vary within and between tissues in the same eukaryotic organism, we speculate that matching of tRNA availability to codon usage may be one determinant of the restriction of expression of PV late genes to differentiated epithelium. PMID:10233959

Zhou, Jian; Liu, Wen Jun; Peng, Shi Wen; Sun, Xiao Yi; Frazer, Ian

1999-01-01

51

Contrasting Codon Usage Patterns and Purifying Selection at the Mating Locus in Putatively Asexual Alternaria Fungal Species  

PubMed Central

Sexual reproduction in heterothallic ascomycete fungi is controlled by a single mating-type locus called MAT1 with two alternate alleles or idiomorphs, MAT1-1 and MAT1-2. These alleles lack sequence similarity and encode different transcriptional regulators. A large number of phytopathogenic fungi including Alternaria spp. are considered asexual, yet still carry expressed MAT1 genes. The molecular evolution of Alternaria MAT1 was explored using nucleotide diversity, nonsynonymous vs. synonymous substitution (dn/ds) ratios and codon usage statistics. Likelihood ratio tests of site-branch models failed to detect positive selection on MAT1-1-1 or MAT1-2-1. Codon-site models demonstrated that both MAT1-1-1 and MAT1-2-1 are under purifying selection and significant differences in codon usage were observed between MAT1-1-1 and MAT1-2-1. Mean GC content at the third position (GC3) and effective codon usage (ENC) were significantly different between MAT1-1-1 and MAT1-2-1 with values of 0.57 and 48 for MAT1-1-1 and 0.62 and 46 for MAT1-2-1, respectively. In contrast, codon usage of Pleospora spp. (anamorph Stemphylium), a closely related Dothideomycete genus, was not significantly different between MAT1-1-1 and MAT1-2-1. The purifying selection and biased codon usage detected at the MAT1 locus in Alternaria spp. suggest a recent sexual past, cryptic sexual present and/or that MAT1 plays important cellular role(s) in addition to mating. PMID:21625561

Stewart, Jane E.; Kawabe, Masato; Abdo, Zaid; Arie, Tsutomu; Peever, Tobin L.

2011-01-01

52

Investigation on the causes of codon and amino acid usages variation between thermophilic Aquifex aeolicus and mesophilic Bacillus subtilis.  

PubMed

Base composition, codon usages and amino acid usages have been analyzed by taking 529 orthologous sequences of Aquifex aeolicus and Bacillus subtilis, having different optimal growth temperatures. These two bacteria do not have significant difference in overall GC composition, but GC(1+2) and GC3 levels were found to vary significantly. Significant increments in purine content and GC3 composition have been observed in the coding sequences of Aquifex aeolicus than its Bacillus subtilis counterparts. Correspondence analyses on codon and amino acid usages reveal that variation in base composition actually influences their codon and amino acid usages. Two selection pressures acting on the nucleotide level (GC3 and purine enrichment), causes variation in the amino acid usage differently in different protein secondary structures. Our results suggest that adaptation of amino acid usages in coil structure of Aquifex aeolicus proteins is under the control of both purine increment and GC3 composition, whereas the adaptation of the amino acids in the helical region of thermophilic bacteria is strongly influenced by the purine content. Evolutionary perspectives concerning the temperature adaptation of DNA and protein molecules of these two bacteria have been discussed on the basis of these results. PMID:15317481

Basak, S; Banerjee, T; Gupta, S K; Ghosh, T C

2004-10-01

53

Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in Hemagglutinin Gene in H1N1 Subtype of Influenza A Virus  

PubMed Central

It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. Influenza A virus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenza A viruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenza A virus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences were A redundant with most codons preferring nucleotide A over others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus. PMID:25140301

Chakraborty, Supriyo

2014-01-01

54

Do universal codon-usage patterns minimize the effects of mutation and translation error?  

Microsoft Academic Search

BACKGROUND: Do species use codons that reduce the impact of errors in translation or replication? The genetic code is arranged in a way that minimizes errors, defined as the sum of the differences in amino-acid properties caused by single-base changes from each codon to each other codon. However, the extent to which organisms optimize the genetic messages written in this

Roberto Marquez; Sandra Smit; Rob Knight

2005-01-01

55

Reduced Efficacy of Natural Selection on Codon Usage Bias in Selfing Arabidopsis and Capsella Species  

PubMed Central

Population genetic theory predicts that the efficacy of natural selection in a self-fertilizing species should be lower than its outcrossing relatives because of the reduction in the effective population size (Ne) in the former brought about by inbreeding. However, previous analyses comparing Arabidopsis thaliana (selfer) with A. lyrata (outcrosser) have not found conclusive support for this prediction. In this study, we addressed this issue by examining silent site polymorphisms (synonymous and intronic), which are expected to be informative about changes in Ne. Two comparisons were made: A. thaliana versus A. lyrata and Capsella rubella (selfer) versus C. grandiflora (outcrosser). Extensive polymorphism data sets were obtained by compiling published data from the literature and by sequencing 354 exon loci in C. rubella and 89 additional loci in C. grandiflora. To extract information from the data effectively for studying these questions, we extended two recently developed models in order to investigate detailed selective differences between synonymous codons, mutational biases, and biased gene conversion (BGC), taking into account the effects of recent changes in population size. We found evidence that selection on synonymous codons is significantly weaker in the selfers compared with the outcrossers and that this difference cannot be fully accounted for by mutational biases or BGC. PMID:21856647

Qiu, Suo; Zeng, Kai; Slotte, Tanja; Wright, Stephen; Charlesworth, Deborah

2011-01-01

56

Mitochondrial phylogenomics of early land plants: mitigating the effects of saturation, compositional heterogeneity, and codon-usage bias.  

PubMed

Phylogenetic analyses using concatenation of genomic-scale data have been seen as the panacea for resolving the incongruences among inferences from few or single genes. However, phylogenomics may also suffer from systematic errors, due to the, perhaps cumulative, effects of saturation, among-taxa compositional (GC content) heterogeneity, or codon-usage bias plaguing the individual nucleotide loci that are concatenated. Here, we provide an example of how these factors affect the inferences of the phylogeny of early land plants based on mitochondrial genomic data. Mitochondrial sequences evolve slowly in plants and hence are thought to be suitable for resolving deep relationships. We newly assembled mitochondrial genomes from 20 bryophytes, complemented these with 40 other streptophytes (land plants plus algal outgroups), compiling a data matrix of 60 taxa and 41 mitochondrial genes. Homogeneous analyses of the concatenated nucleotide data resolve mosses as sister-group to the remaining land plants. However, the corresponding translated amino acid data support the liverwort lineage in this position. Both results receive weak to moderate support in maximum-likelihood analyses, but strong support in Bayesian inferences. Tests of alternative hypotheses using either nucleotide or amino acid data provide implicit support for their respective optimal topologies, and clearly reject the hypotheses that bryophytes are monophyletic, liverworts and mosses share a unique common ancestor, or hornworts are sister to the remaining land plants. We determined that land plant lineages differ in their nucleotide composition, and in their usage of synonymous codon variants. Composition heterogeneous Bayesian analyses employing a nonstationary model that accounts for variation in among-lineage composition, and inferences from degenerated nucleotide data that avoid the effects of synonymous substitutions that underlie codon-usage bias, again recovered liverworts being sister to the remaining land plants but without support. These analyses indicate that the inference of an early-branching moss lineage based on the nucleotide data is caused by convergent compositional biases. Accommodating among-site amino acid compositional heterogeneity (CAT-model) yields no support for the optimal resolution of liverwort as sister to the rest of land plants, suggesting that the robust inference of the liverwort position in homogeneous analyses may be due in part to compositional biases among sites. All analyses support a paraphyletic bryophytes with hornworts composing the sister-group to tracheophytes. We conclude that while genomic data may generate highly supported phylogenetic trees, these inferences may be artifacts. We suggest that phylogenomic analyses should assess the possible impact of potential biases through comparisons of protein-coding gene data and their amino acid translations by evaluating the impact of substitutional saturation, synonymous substitutions, and compositional biases through data deletion strategies and by analyzing the data using heterogeneous composition models. We caution against relying on any one presentation of the data (nucleotide or amino acid) or any one type of analysis even when analyzing large-scale data sets, no matter how well-supported, without fully exploring the effects of substitution models. PMID:25070972

Liu, Yang; Cox, Cymon J; Wang, Wei; Goffinet, Bernard

2014-11-01

57

Codon usage bias and tRNA over-expression in Buchnera aphidicola after aromatic amino acid nutritional stress on its host Acyrthosiphon pisum  

PubMed Central

Codon usage bias and relative abundances of tRNA isoacceptors were analysed in the obligate intracellular symbiotic bacterium, Buchnera aphidicola from the aphid Acyrthosiphon pisum, using a dedicated 35mer oligonucleotide microarray. Buchnera is archetypal of organisms living with minimal metabolic requirements and presents a reduced genome with high-evolutionary rate. Codonusage in Buchnera has been overcome by the high mutational bias towards AT bases. However, several lines of evidence for codon usage selection are given here. A significant correlation was found between tRNA relative abundances and codon composition of Buchnera genes. A significant codon usage bias was found for the choice of rare codons in Buchnera: C-ending codons are preferred in highly expressed genes, whereas G-ending codons are avoided. This bias is not explained by GC skew in the bacteria and might correspond to a selection for perfect matching between codon–anticodon pairs for some essential amino acids in Buchnera proteins. Nutritional stress applied to the aphid host induced a significant overexpression of most of the tRNA isoacceptors in bacteria. Although, molecular regulation of the tRNA operons in Buchnera was not investigated, a correlation between relative expression levels and organization in transcription unit was found in the genome of Buchnera. PMID:16963497

Charles, Hubert; Calevro, Federica; Vinuelas, Jose; Fayard, Jean-Michel; Rahbe, Yvan

2006-01-01

58

Gene Expression Levels Are Correlated with Synonymous Codon Usage, Amino Acid Composition, and Gene Architecture in the Red Flour Beetle, Tribolium castaneum  

PubMed Central

Gene expression levels correlate with multiple aspects of gene sequence and gene structure in phylogenetically diverse taxa, suggesting an important role of gene expression levels in the evolution of protein-coding genes. Here we present results of a genome-wide study of the influence of gene expression on synonymous codon usage, amino acid composition, and gene structure in the red flour beetle, Tribolium castaneum. Consistent with the action of translational selection, we find that synonymous codon usage bias increases with gene expression. However, the correspondence between tRNA gene copy number and optimal codons is weak. At the amino acid level, translational selection is suggested by the positive correlation between tRNA gene numbers and amino acid usage, which is stronger for highly expressed genes. In addition, there is a clear trend for increased use of metabolically cheaper, less complex amino acids as gene expression increases. tRNA gene numbers also correlate negatively with amino acid size/complexity (S/C) score indicating the coupling between translational selection and selection to minimize the use of large/complex amino acids. Interestingly, the analysis of 10 additional genomes suggests that the correlation between tRNA gene numbers and amino acid S/C score is widespread and might be explained by selection against negative consequences of protein misfolding. At the level of gene structure, three major trends are detected: 1) complete coding region length increases across low and intermediate expression levels but decreases in highly expressed genes; 2) the average intron size shows the opposite trend, first decreasing with expression, followed by a slight increase in highly expressed genes; and 3) intron density remains nearly constant across all expression levels. These changes in gene architecture are only in partial agreement with selection favoring reduced cost of biosynthesis. PMID:22826459

Williford, Anna; Demuth, Jeffery P.

2012-01-01

59

Evident diversity of codon usage patterns of human genes with respect to chromosome banding patterns and chromosome numbers; relation between nucleotide sequence data and cytogenetic data.  

PubMed Central

The sequences of the human genome compiled in DNA databases are now about 10 megabase pairs (Mb), and thus the size of the sequences is several times the average size of chromosome bands at high resolution. By surveying this large quantity of data, it may be possible to clarify the global characteristics of the human genome, that is, correlation of gene sequence data (kb-level) to cytogenetic data (Mb-level). By extensively searching the GenBank database, we calculated codon usages in about 2000 human sequences. The highest G + C percentage at the third codon position was 97%, and that of about 250 sequences was 80% or more. The lowest G + C% was 27%, and that in about 150 sequences was 40% or less. A major portion of the GC-rich genes was found to be on special subsets of R-bands (T-bands and/or terminal R-bands). AT-rich genes, however, were mainly on G-bands or non-T-type internal R-bands. Average G + C% at the third position for individual chromosomes differed among chromosomes, and were related to T-band density, quinacrine dullness, and mitotic chiasmata density in the respective chromosomes. PMID:1886761

Ikemura, T; Wada, K

1991-01-01

60

Secret Codon  

NSDL National Science Digital Library

In this activity, "write" a secret message in genetic code as beads on a string. Learners use an amino acid codon table to determine the DNA sequences that correspond to the one-letter amino acid abbreviations that make up their secret word(s). Learners also use start and stop codons in their sequences and follow a color key for the bases. Learners can trade strands with a friend to see if they can decode their secret message.

Yu, Julie

2008-01-01

61

Codon frequencies in 119 individual genes confirm consistent choices of degenerate bases according to genome type.  

PubMed Central

The poor printing of our previous Figure 2 (1) is corrected. Codon usage in mRNA sequences just published is also given. A new correspondence analysis is done, based on simultaneous comparison in all mRNA of use of the 61 codons. This analysis reinforces our claim that most genes in a genome, or genome type, have the same coding strategy; that is, they show similar choices among synonymous codons, or among degenerate bases (2). Like analysis on frequency variation in the amino acids coded reveals an entirely different pattern. PMID:6159596

Grantham, R; Gautier, C; Gouy, M

1980-01-01

62

A Shift in the Third-Codon-Position Nucleotide Frequency in Alcohol Dehydrogenase Genes in the Genus Drosophila  

Microsoft Academic Search

Examination of the relative frequency of occurrence of alternative synonymous codons for any one amino acid (codon usage) for proteins within and among species suggests that codon usage pattern is a significant component of both genomic expression and expression of individual genes. This generalization implies a functional role of codon usage and that synonymous substitution rates may differ between lineages

William T. Starmer; David T. Sullivan

63

The Comparison of Usage and Availability Measurements for Evaluating Resource Preference  

Microsoft Academic Search

Abstract. Modern ecological research often involves the comparison of the usage of habitat types or food items to the availability of those resources to the animal. Widely used methods of determining preference from measurements of usage and availability depend critically on the array of components

Douglas H. Johnson

1980-01-01

64

Effect of Codon Message on Xylanase Thermal Activity*  

PubMed Central

Because the genetic codon is known for degeneracy, its effect on enzyme thermal property is seldom investigated. A dataset was constructed for GH10 xylanase coding sequences and optimal temperatures for activity (Topt). Codon contents and relative synonymous codon usages were calculated and respectively correlated with the enzyme Topt values, which were used to describe the xylanase thermophilic tendencies without dividing them into two thermophilic and mesophilic groups. After analyses of codon content and relative synonymous codon usages were checked by the Bonferroni correction, we found five codons, with three (AUA, AGA, and AGG) correlating positively and two (CGU and AGC) correlating negatively with the Topt value. The three positive codons are purine-rich codons, and the two negative codons have A-ends. The two negative codons are pyridine-rich codons, and one has a C-end. Comparable with the codon C- and A-ending features, C- and A-content within mRNA correlated negatively and positively with the Topt value, respectively. Thereby, codons have effects on enzyme thermal property. When the issue is analyzed at the residual level, the effect of codon message is lost. The codons relating to enzyme thermal property are selected by thermophilic force at nucleotide level. PMID:22707716

Liu, Liangwei; Wang, Linmin; Zhang, Zhang; Wang, Suya; Chen, Hongge

2012-01-01

65

Cellular immunity survey against urinary tract infection using pVAX/fimH cassette with mammalian and wild type codon usage as a DNA vaccine  

PubMed Central

Purpose FimH (the adhesion fragment of type 1 fimbriae) is implicated in uropathogenic Escherichia coli (UPEC) attachment to epithelial cells through interaction with mannose. Recently, some studies have found that UPEC can thrive intracellularly causing recurrent urinary tract infection (UTI). Almost all vaccines have been designed to induce antibodies against UPEC. Yet, the humoral immune response is not potent enough to overcome neither the primary UTI nor recurrent infections. However, DNA vaccines offer the possibility of inducing cell mediated immune responses and may be a promising preventive tool. Materials and Methods In this study, we employed two different open reading frames within mammalian (mam) and wild type (wt) codons of fimH gene. Optimized fragments were cloned in pVAX-1. Expression of the protein in COS-7 was confirmed by western blot analysis after assessing pVAX/fimH(mam) and pVAX/fimH(wt). The constructs were injected to BALB/c mice at plantar surface of feet followed by electroporation. Results The mice immunized with both constructs following booster injection with recombinant FimH showed increased interferon-? and interleukin-12 responses significantly higher than non-immunized ones (p<0.05). The immunized mice were challenged with UPEC and then the number of bacteria recovered from the immunized mice was compared with the non-immunized ones. Decreased colony count in immunized mice along with cytokine responses confirmed the promising immune response by the DNA vaccines developed in this study. Conclusion In conclusion, DNA vaccines of UPEC proteins may confer some levels of protection which can be improved by multiple constructs or boosters. PMID:25003092

Bagherpour, Ghasem; Khoramabadi, Nima; Fallah Mehrabadi, Jalil; Mahdavi, Mehdi; Halabian, Raheleh; Amin, Mohsen; Izadi Mobarakeh, Jalal; Einollahi, Behzad

2014-01-01

66

A codon-usage variant in the (GGN){sub n} trinucleotide polymorphism of the androgen receptor gene as an aid in the prenatal diagnosis of ambiguous genitalia due to partial androgen insensitivity  

SciTech Connect

Exon 1 at the X-linked androgen receptor (AR) locus encodes an N-terminal modulatory domain that contains two large homopolyamino acid tracts: (CAG;glutamine;Gln){sub 11-33} and (GGN;Glycine;Cly){sub 15-27}. Certain AR mutations cause partial androgen insensitivity (PAI) with frank genital ambiguity that may engender appreciable parental anxiety and patient morbidity. If the AR mutation in a PAI family is unknown, the AR`s intragenic trinucleotide repeat polymorphisms may be used for prenatal diagnosis. However, intergenerational instability of repeat-size may be worrisome, particularly when the information alleles differ by only a few repeats. Here, we report the discovery of a codon-usage (silent substitution) variant in the GGN repeat, and describe its use as a source of complementary information for prenatal diagnosis. The standard sense sequence of the (GGN){sub n} tract is (GGT){sub 3} GGG(GGT){sub 2} (GGC){sub 9-21}. On 4 of 27 X chromosomes we noted that the internal GGT sequence was expanded to 3 or 4 repeats. We used an internal (GGT){sub 4} repeat in a total (GGN){sub 24} tract together with a (CAG){sub 20} tract to distinguish an X chromosome with a mutant AR allele from another X chromosome, bearing a normal allele, that had an internal (GGT){sub 2} repeat in a total (GGN){sub 23} tract together with a (CAG){sub 21} tract. Subsequently, we found the base change leading to a pathogenic amino acid substitution (M779I) in codon 6 of the mutant AR gene in an affected maternal aunt and the fetus at risk. This confirmed the prenatal diagnosis based on the intragenic trinucleotide repeat polymorphisms, and it strengthened the prediction of external genital ambiguity using our previous experience with M779I in another family.

Lumbroso, R.; Vasiliou, M.; Beitel, L.K. [McGill Univ., Montreal, Quebec (Canada)] [and others

1994-09-01

67

[The comparison of the micro-syringe with clinical usage].  

PubMed

Micro-syringe as a result of the high frequency of clinical use, direct contact with patients, the failure of its equipment will have a direct impact on the patient's disease status. Researchers in this paper, by simulating the test fluid, electrical safety testing and analysis of statistical methods such as maintenance records, consider six kinds of common injection pump, in terms of performance, safety and the failure rate of three performance. Compared the performance analysis, summarized the various types of injection pump characteristics, researchers make suggestions to clinical departments, equipment procurement and equipment management departments for usage and improvement. PMID:25330618

Peng, Junyan; Qian, Jianguo; Zhang, Lei

2014-07-01

68

ICT Usage of Pre-service Teachers: Cultural Comparison for Turkey and Bosnia and Herzegovina  

ERIC Educational Resources Information Center

The importance of ICTs has become the undisputed in the present century. Studies have been conducted to investigate the use of ICTs with the goal of increase in quality of teacher education for a long time. This study is a cross-cultural comparison in terms of pre-service teachers' level of ICT usage, ICT knowledge and attitudes. The study…

Demirli, Cihad

2013-01-01

69

The comparison of usage and availability measurements for evaluating resource preference  

USGS Publications Warehouse

Modern ecological research often involves the comparison of the usage of habitat types or food items to the availability of those resources to the animal. Widely used methods of determining preference from measurements of usage and availability depend critically on the array of components that the researcher, often with a degree of arbitrariness, deems available to the animal. This paper proposes a new method, based on ranks of components by usage and by availability. A virtue of the rank procedure is that it provides comparable results whether a questionable component is included or excluded from consideration. Statistical tests of significance are given for the method.The paper also offers a hierarchical ordering of selection processes. This hierarchy resolves certain inconsistencies among studies of selection and is compatible with the analytic technique offered in the paper.

Johnson, D.H.

1980-01-01

70

Selection on codon bias in yeast: a transcriptional hypothesis  

PubMed Central

Codons that code for the same amino acid are often used with unequal frequencies. This phenomenon is termed codon bias. Here, we report a computational analysis of codon bias in yeast using experimental and theoretical genome-wide data. We show that the most used codons in highly expressed genes can be predicted by mRNA structural data and that the codon choice at each synonymous site within an mRNA is not random with respect to the local secondary structure. Because we also found that the folding stability of intron sequences is strongly correlated with codon bias and mRNA level, our results suggest that codon bias is linked to mRNA folding structure through a mechanism that, at least partially, operates before pre-mRNA splicing. Consistent with this, we report evidence supporting the adaptation of the tRNA pool to the codon profile of the most expressed genes rather than vice versa. We show that the correlation of codon usage with the gene expression level also includes the stop codons that are normally not decoded by aminoacyl-tRNAs. The results reported here are consistent with a role for transcriptional forces in driving codon usage bias via a mechanism that improves gene expression by optimizing mRNA folding structures. PMID:23945943

Trotta, Edoardo

2013-01-01

71

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

PubMed Central

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

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

2002-01-01

72

GC constituents and relative codon expressed amino acid composition in cyanobacterial phycobiliproteins.  

PubMed

The genomic as well as structural relationship of phycobiliproteins (PBPs) in different cyanobacterial species are determined by nucleotides as well as amino acid composition. The genomic GC constituents influence the amino acid variability and codon usage of particular subunit of PBPs. We have analyzed 11 cyanobacterial species to explore the variation of amino acids and causal relationship between GC constituents and codon usage. The study at the first, second and third levels of GC content showed relatively more amino acid variability on the levels of G3+C3 position in comparison to the first and second positions. The amino acid encoded GC rich level including G rich and C rich or both correlate the codon variability and amino acid availability. The fluctuation in amino acids such as Arg, Ala, His, Asp, Gly, Leu and Glu in ? and ? subunits was observed at G1C1 position; however, fluctuation in other amino acids such as Ser, Thr, Cys and Trp was observed at G2C2 position. The coding selection pressure of amino acids such as Ala, Thr, Tyr, Asp, Gly, Ile, Leu, Asn, and Ser in ? and ? subunits of PBPs was more elaborated at G3C3 position. In this study, we observed that each subunit of PBPs is codon specific for particular amino acid. These results suggest that genomic constraint linked with GC constituents selects the codon for particular amino acids and furthermore, the codon level study may be a novel approach to explore many problems associated with genomics and proteomics of cyanobacteria. PMID:24933001

Kannaujiya, Vinod K; Rastogi, Rajesh P; Sinha, Rajeshwar P

2014-08-10

73

Ecological Adaptation in Bacteria: Speciation Driven by Codon Selection  

PubMed Central

In bacteria, physiological change may be effected by a single gene acquisition, producing ecological differentiation without genetic isolation. Natural selection acting on such differences can reduce the frequency of genotypes that arise from recombination at these loci. However, gene acquisition can only account for recombination interference in the fraction of the genome that is tightly linked to the integration site. To identify additional loci that contribute to adaptive differences, we examined orthologous genes in species of Enterobacteriaceae to identify significant differences in the degree of codon selection. Significance was assessed using the Adaptive Codon Enrichment metric, which accounts for the variation in codon usage bias that is expected to arise from mutation and drift; large differences in codon usage bias were identified in more genes than would be expected to arise from stochastic processes alone. Genes in the same operon showed parallel differences in codon usage bias, suggesting that changes in the overall levels of gene expression led to changes in the degree of adaptive codon usage. Most significant differences between orthologous operons were found among those involved with specific environmental adaptations, whereas "housekeeping" genes rarely showed significant changes. When considered together, the loci experiencing significant changes in codon selection outnumber potentially adaptive gene acquisition events. The identity of genes under strong codon selection seems to be influenced by the habitat from which the bacteria were isolated. We propose a two-stage model for how adaptation to different selective regimes can drive bacterial speciation. Initially, gene acquisitions catalyze rapid ecological differentiation, which modifies the utilization of genes, thereby changing the strength of codon selection on them. Alleles develop fitness variation by substitution, producing recombination interference at these loci in addition to those flanking acquired genes, allowing sequences to diverge across the entire genome and establishing genetic isolation (i.e., protection from frequent homologous recombination). PMID:22740635

Retchless, Adam C.; Lawrence, Jeffrey G.

2012-01-01

74

Codon Optimization of Gene Fragments Encoding Plasmodium falciparum Merzoite Proteins Enhances DNA Vaccine Protein Expression and Immunogenicity in Mice  

Microsoft Academic Search

In contrast to conventional vaccines, DNA and other subunit vaccines exclusively utilize host cell molecules for transcription and translation of proteins. The adenine plus thymine content of Plasmodium falciparum gene sequences (80%) is much greater than that of Homo sapiens (59%); consequently, codon usage is markedly different. We hypothesized that modifying codon usage of P. falciparum genes encoded by DNA

DAVID L. NARUM; SANJAI KUMAR; WILLIAM O. ROGERS; STEVEN R. FUHRMANN; HONG LIANG; MIRANDA OAKLEY; ALEM TAYE; B. KIM LEE SIM; STEPHEN L. HOFFMAN

2001-01-01

75

Journal of Theoretical Biology 239 (2006) 417434 A model of protein translation including codon bias, nonsense errors,  

E-print Network

and confirm that nonsense errors can play an important role in shaping codon usage bias. r 2005 Elsevier Ltd bias, nonsense errors, and ribosome recycling Michael A. Gilchrista,�, Andreas Wagnerb a Department errors and codon usage bias can have a large effect on the probability that a ribosome will completely

Wagner, Andreas

76

Codon populations in single-stranded whole human genome DNA Are fractal and fine-tuned by the Golden Ratio 1.618  

Microsoft Academic Search

This new bioinformatics research bridges Genomics and Mathematics. We propose a universal “Fractal Genome Code Law”: The frequency\\u000a of each of the 64 codons across the entire human genome is controlled by the codon’s position in the Universal Genetic Code\\u000a table. We analyze the frequency of distribution of the 64 codons (codon usage) within single-stranded DNA sequences. Concatenating\\u000a 24 Human

Jean-Claude Perez

2010-01-01

77

The Effect of Mutation and Selection on Codon Adaptation in Escherichia coli Bacteriophage  

PubMed Central

Studying phage codon adaptation is important not only for understanding the process of translation elongation, but also for reengineering phages for medical and industrial purposes. To evaluate the effect of mutation and selection on phage codon usage, we developed an index to measure selection imposed by host translation machinery, based on the difference in codon usage between all host genes and highly expressed host genes. We developed linear and nonlinear models to estimate the C?T mutation bias in different phage lineages and to evaluate the relative effect of mutation and host selection on phage codon usage. C?T-biased mutations occur more frequently in single-stranded DNA (ssDNA) phages than in double-stranded DNA (dsDNA) phages and affect not only synonymous codon usage, but also nonsynonymous substitutions at second codon positions, especially in ssDNA phages. The host translation machinery affects codon adaptation in both dsDNA and ssDNA phages, with a stronger effect on dsDNA phages than on ssDNA phages. Strand asymmetry with the associated local variation in mutation bias can significantly interfere with codon adaptation in both dsDNA and ssDNA phages. PMID:24583580

Chithambaram, Shivapriya; Prabhakaran, Ramanandan; Xia, Xuhua

2014-01-01

78

Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus  

E-print Network

Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus, 2003) Although the surface proteins of human influenza A virus evolve rapidly and continually produce the sequence evolution of three influenza A genes over the past two decades. We study codon usage

Plotkin, Joshua B.

79

Mammalian Mutation Pressure, Synonymous Codon Choice, and mRNA Degradation  

Microsoft Academic Search

The usage of synonymous codons (SCs) in mammalian genes is highly correlated with local base composition and is therefore thought to be determined by mutation pressure. The usage is nonetheless structured. For instance, mammals share with Saccharomyces and Drosophila most preferences for the C-ending over the G-ending codon (or vice versa) within each fourfold-degenerate SC family and the fact that

Jubao Duan; Marcos A. Antezana

2003-01-01

80

Effect of codon-optimized E. coli signal peptides on recombinant Bacillus stearothermophilus maltogenic amylase periplasmic localization, yield and activity.  

PubMed

Recombinant proteins can be targeted to the Escherichia coli periplasm by fusing them to signal peptides. The popular pET vectors facilitate fusion of target proteins to the PelB signal. A systematic comparison of the PelB signal with native E. coli signal peptides for recombinant protein expression and periplasmic localization is not reported. We chose the Bacillus stearothermophilus maltogenic amylase (MA), an industrial enzyme widely used in the baking and brewing industry, as a model protein and analyzed the competence of seven, codon-optimized, E. coli signal sequences to translocate MA to the E. coli periplasm compared to PelB. MA fusions to three of the signals facilitated enhanced periplasmic localization of MA compared to the PelB fusion. Interestingly, these three fusions showed greatly improved MA yields and between 18- and 50-fold improved amylase activities compared to the PelB fusion. Previously, non-optimal codon usage in native E. coli signal peptide sequences has been reported to be important for protein stability and activity. Our results suggest that E. coli signal peptides with optimal codon usage could also be beneficial for heterologous protein secretion to the periplasm. Moreover, such fusions could even enhance activity rather than diminish it. This effect, to our knowledge has not been previously documented. In addition, the seven vector platform reported here could also be used as a screen to identify the best signal peptide partner for other recombinant targets of interest. PMID:25038884

Samant, Shalaka; Gupta, Gunja; Karthikeyan, Subbulakshmi; Haq, Saiful F; Nair, Ayyappan; Sambasivam, Ganesh; Sukumaran, Sunilkumar

2014-09-01

81

Codon Preference Optimization Increases Heterologous PEDF Expression  

PubMed Central

Pigment epithelium-derived factor (PEDF) is widely known for its neurotrophic and antiangiogenic functions. Efficacy studies of PEDF in animal models are limited because of poor heterologous protein yields. Here, we redesigned the human PEDF gene to preferentially match codon frequencies of E coli without altering the amino acid sequence. Following de novo synthesis, codon optimized PEDF (coPEDF) and the wtPEDF genes were cloned into pET32a containing a 5? thioredoxin sequence (Trx) and the recombinant Trx-coPEDF or Trx-wtPEDF fusion constructs expressed in native and two tRNA augmented E coli hosts - BL21-CodonPlus(DE3)-RIL and BL21-CodonPlus(DE3)-RP, carrying extra copies of tRNAarg,ile,leu and tRNAarg,pro genes , respectively. Trx-PEDF fusion proteins were isolated using Ni-NTA metal affinity chromatography and PEDF purified after cleavage with factor X?. Protein purity and identity were confirmed by western blot, MALDI-TOF, and UV/CD spectral analyses. Expression of the synthetic gene was ?3.4 fold greater (212.7 mg/g; 62.1 mg/g wet cells) and purified yields ?4 fold greater (41.1 mg/g; 11.3 mg/g wet cell) than wtPEDF in the native host. A small increase in expression of both genes was observed in hosts supplemented with rare tRNA genes compared to the native host but expression of coPEDF was ?3 fold greater than wtPEDF in both native and codon-bias-adjusted E coli strains. ?Gs at ?3 to +50 of the Trx site of both fusion genes were ?3.9 kcal/mol. Functionally, coPEDF was equally as effective as wtPEDF in reducing oxidative stress, promoting neurite outgrowth, and blocking endothelial tube formation. These findings suggest that while rare tRNA augmentation and mRNA folding energies can significantly contribute to increased protein expression, preferred codon usage, in this case, is advantageous to translational efficiency of biologically active PEDF in E coli. This strategy will undoubtedly fast forward studies to validate therapeutic utility of PEDF in vivo. PMID:21152082

Gvritishvili, Anzor G.; Leung, Kar Wah; Tombran-Tink, Joyce

2010-01-01

82

A Generalized Mechanistic Codon Model  

PubMed Central

Models of codon evolution have attracted particular interest because of their unique capabilities to detect selection forces and their high fit when applied to sequence evolution. We described here a novel approach for modeling codon evolution, which is based on Kronecker product of matrices. The 61 × 61 codon substitution rate matrix is created using Kronecker product of three 4 × 4 nucleotide substitution matrices, the equilibrium frequency of codons, and the selection rate parameter. The entities of the nucleotide substitution matrices and selection rate are considered as parameters of the model, which are optimized by maximum likelihood. Our fully mechanistic model allows the instantaneous substitution matrix between codons to be fully estimated with only 19 parameters instead of 3,721, by using the biological interdependence existing between positions within codons. We illustrate the properties of our models using computer simulations and assessed its relevance by comparing the AICc measures of our model and other models of codon evolution on simulations and a large range of empirical data sets. We show that our model fits most biological data better compared with the current codon models. Furthermore, the parameters in our model can be interpreted in a similar way as the exchangeability rates found in empirical codon models. PMID:24958740

Zaheri, Maryam; Dib, Linda; Salamin, Nicolas

2014-01-01

83

Usage Bibliometrics  

NASA Astrophysics Data System (ADS)

Scholarly usage data provides unique opportunities to address the known shortcomings of citation analysis. However, the collection, processing and analysis of usage data remains an area of active research. This article provides a review of the state-of-the-art in usage-based informetric, i.e. the use of usage data to study the scholarly process.

Kurtz, Michael J.; Bollen, Johan

2010-01-01

84

Ambushing the ambush hypothesis: predicting and evaluating off-frame codon frequencies in Prokaryotic Genomes  

PubMed Central

Background In this paper, we address the evidence for the Ambush Hypothesis. Proposed by Seligmann and Pollock, this hypothesis posits that there exists a selection for off-frame stop codons (OSCs) to counteract the possible deleterious effects of translational frameshifts, including the waste of resources and potential cytotoxicity. Two main types of study have been used to support the hypothesis. Some studies analyzed codon usage and showed that codons with more potential to create OSCs seem to be favored over codons with lower potential; they used this finding to support the Ambush Hypothesis. Another study used 342 bacterial genomes to evaluate the hypothesis directly, finding significant excesses of OSCs in these genomes. Results We repeated both analyses with newer datasets and searched for other factors that could explain the observed trends. In the first case, the relative frequency of codons with the potential to create OSCs is directly correlated with the GC content of organisms, as stop codons are GC-poor. When evaluating the frequency of OSCs directly in 1,976 bacterial genomes we also detected a significant excess. However, when comparing the excess of OSCs with similarly obtained results for the frequency of out-of-frame sense codons, some sense codons have a more significant excess than stop codons. Conclusions Two avenues of study have been used to support the Ambush Hypothesis. Using the same methods as these previous studies, we demonstrate that the evidence in support of the Ambush Hypothesis does not hold up against more rigorous testing. PMID:23799949

2013-01-01

85

Replicational and transcriptional selection on codon usage in Borrelia burgdorferi  

Microsoft Academic Search

With more than 10 fully sequenced, publicly available prokaryotic genomes, it is now becoming possible to gain useful insights into genome evolution. Before the genome era, many evolutionary processes were evaluated from limited data sets and evolutionary models were constructed on the basis of small amounts of evidence. In this paper, I show that genes on the Borrelia burgdorferi genome

JAMES O. MCINERNEY

1998-01-01

86

Positive selection for unpreferred codon usage in eukaryotic genomes  

E-print Network

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 ...

Neafsey, Daniel E.

87

The Levels of Speech Usage Rating Scale: Comparison of Client Self-Ratings with Speech Pathologist Ratings  

ERIC Educational Resources Information Center

Background: The term "speech usage" refers to what people want or need to do with their speech to fulfil the communication demands in their life roles. Speech-language pathologists (SLPs) need to know about clients' speech usage to plan appropriate interventions to meet their life participation goals. The Levels of Speech Usage is a categorical…

Gray, Christina; Baylor, Carolyn; Eadie, Tanya; Kendall, Diane; Yorkston, Kathryn

2012-01-01

88

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

PubMed

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

Nabiyouni, Maryam; Prakash, Ashwin; Fedorov, Alexei

2013-04-25

89

In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein.  

PubMed

The evolution of codon bias, the unequal usage of synonymous codons, is thought to be due to natural selection for the use of preferred codons that match the most abundant species of isoaccepting tRNA, resulting in increased translational efficiency and accuracy. We examined this hypothesis by introducing 1, 6, and 10 unpreferred codons into the Drosophila alcohol dehydrogenase gene (Adh). We observed a significant decrease in ADH protein production with number of unpreferred codons, confirming the importance of natural selection as a mechanism leading to codon bias. We then used this empirical relationship to estimate the selection coefficient (s) against unpreferred synonymous mutations and found the value (s >or= 10(-5)) to be approximately one order of magnitude greater than previous estimates from population genetics theory. The observed differences in protein production appear to be too large to be consistent with current estimates of the strength of selection on synonymous sites in D. melanogaster. PMID:12586711

Carlini, David B; Stephan, Wolfgang

2003-01-01

90

Selection on synonymous codons in mammalian rhodopsins: a possible role in optimizing translational processes  

PubMed Central

Background Synonymous codon usage can affect many cellular processes, particularly those associated with translation such as polypeptide elongation and folding, mRNA degradation/stability, and splicing. Highly expressed genes are thought to experience stronger selection pressures on synonymous codons. This should result in codon usage bias even in species with relatively low effective population sizes, like mammals, where synonymous site selection is thought to be weak. Here we use phylogenetic codon-based likelihood models to explore patterns of codon usage bias in a dataset of 18 mammalian rhodopsin sequences, the protein mediating the first step in vision in the eye, and one of the most highly expressed genes in vertebrates. We use these patterns to infer selection pressures on key translational mechanisms including polypeptide elongation, protein folding, mRNA stability, and splicing. Results Overall, patterns of selection in mammalian rhodopsin appear to be correlated with post-transcriptional and translational processes. We found significant evidence for selection at synonymous sites using phylogenetic mutation-selection likelihood models, with C-ending codons found to have the highest relative fitness, and to be significantly more abundant at conserved sites. In general, these codons corresponded with the most abundant tRNAs in mammals. We found significant differences in codon usage bias between rhodopsin loops versus helices, though there was no significant difference in mean synonymous substitution rate between these motifs. We also found a significantly higher proportion of GC-ending codons at paired sites in rhodopsin mRNA secondary structure, and significantly lower synonymous mutation rates in putative exonic splicing enhancer (ESE) regions than in non-ESE regions. Conclusions By focusing on a single highly expressed gene we both distinguish synonymous codon selection from mutational effects and analytically explore underlying functional mechanisms. Our results suggest that codon bias in mammalian rhodopsin arises from selection to optimally balance high overall translational speed, accuracy, and proper protein folding, especially in structurally complicated regions. Selection at synonymous sites may also be contributing to mRNA stability and splicing efficiency at exonic-splicing-enhancer (ESE) regions. Our results highlight the importance of investigating highly expressed genes in a broader phylogenetic context in order to better understand the evolution of synonymous substitutions. PMID:24884412

2014-01-01

91

Exonic transcription factor binding directs codon choice and affects protein evolution.  

PubMed

Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. We used genomic deoxyribonuclease I footprinting to map nucleotide resolution TF occupancy across the human exome in 81 diverse cell types. We found that ~15% of human codons are dual-use codons ("duons") that simultaneously specify both amino acids and TF recognition sites. Duons are highly conserved and have shaped protein evolution, and TF-imposed constraint appears to be a major driver of codon usage bias. Conversely, the regulatory code has been selectively depleted of TFs that recognize stop codons. More than 17% of single-nucleotide variants within duons directly alter TF binding. Pervasive dual encoding of amino acid and regulatory information appears to be a fundamental feature of genome evolution. PMID:24337295

Stergachis, Andrew B; Haugen, Eric; Shafer, Anthony; Fu, Wenqing; Vernot, Benjamin; Reynolds, Alex; Raubitschek, Anthony; Ziegler, Steven; LeProust, Emily M; Akey, Joshua M; Stamatoyannopoulos, John A

2013-12-13

92

Codon-optimized antibiotic resistance gene improves efficiency of transient transformation in Frankia.  

PubMed

Frankia is a unique actinobacterium having abilities to fix atmospheric dinitrogen and to establish endosymbiosis with trees, but molecular bases underlying these interesting characteristics are poorly understood because of a lack of stable transformation system. Extremely high GC content of Frankia genome (more than 70 percent) can be a hindrance to successful transformation. We generated a synthetic gentamicin resistance gene whose codon usage is optimized to Frankia (fgmR) and evaluated its usefulness as a selection marker using a transient transformation system. Success rate of transient transformation and cell growth in selective culture were significantly increased by use of fgmR instead of a native gentamicin resistance gene, suggesting that codon optimization improved translation efficiency of the marker gene and increased antibiotic resistance. Our result shows that similarity in codon usage pattern is an important factor to be taken into account when exogenous transgenes are expressed in Frankia cells. PMID:24287650

Kucho, Ken-Ichi; Kakoi, Kentaro; Yamaura, Masatoshi; Iwashita, Mari; Abe, Mikiko; Uchiumi, Toshiki

2013-11-01

93

Transcription attenuation in Salmonella typhimurium: the significance of rare leucine codons in the leu leader.  

PubMed Central

The leucine operon of Salmonella typhimurium is controlled by a transcription attenuation mechanism. Four adjacent leucine codons within a 160-nucleotide leu leader RNA are thought to play a central role in this mechanism. Three of the four codons are CUA, a rarely used leucine codon within enteric bacteria. To determine whether the nature of the leucine codon affects the regulation of the leucine operon, we used oligonucleotide-directed mutagenesis to first convert one CUA of the leader to CUG and then convert all three CUA codons to CUG. CUG is the most frequently used leucine codon in enteric bacteria. A mutant having (CUA)2CUGCUC in place of (CUA)3CUC has an altered response to leucine limitation, requiring a slightly higher degree of limitation to effect derepression. Changing (CUA)3CUC to (CUG)3CUC has more dramatic effects upon operon expression. First, the basal level of expression is lowered to the point that the mutant grows more slowly than the parent in a minimal medium lacking leucine. Second, the response of the mutant to a leucine limitation is dramatically altered such that even a strong limitation elicits only a modest degree of derepression. If the mutant is grown under conditions of leucyl-tRNA limitation rather than leucine limitation, complete derepression can be achieved, but only at a much higher degree of limitation than for the wild-type operon. These results provide a clear-cut example of codon usage having a dramatic effect upon gene expression. PMID:3534884

Carter, P W; Bartkus, J M; Calvo, J M

1986-01-01

94

Experimentally increased codon bias in the Drosophila Adh gene leads to an increase in larval, but not adult, alcohol dehydrogenase activity.  

PubMed

Although most amino acids can be encoded by more than one codon, the synonymous codons are not used with equal frequency. This phenomenon is known as codon bias and appears to be a universal feature of genomes. The translational selection hypothesis posits that the use of optimal codons, which match the most abundant species of isoaccepting tRNAs, results in increased translational efficiency and accuracy. Previous work demonstrated that the experimental reduction of codon bias in the Drosophila alcohol dehydrogenase (Adh) gene led to a significant decrease in ADH protein expression. In this study we performed the converse experiment: we replaced seven suboptimal leucine codons that occur naturally in the Drosophila melanogaster Adh gene with the optimal codon. We then compared the in vivo ADH activities imparted by the wild-type and mutant alleles. The introduction of optimal leucine codons led to an increase in ADH activity in third-instar larvae. In adult flies, however, the introduction of optimal codons led to a decrease in ADH activity. There is no evidence that other selectively constrained features of the Adh gene, or its rate of transcription, were altered by the synonymous replacements. These results are consistent with translational selection for codon bias being stronger in the larval stage and suggest that there may be a selective conflict over optimal codon usage between different developmental stages. PMID:19966063

Hense, Winfried; Anderson, Nathan; Hutter, Stephan; Stephan, Wolfgang; Parsch, John; Carlini, David B

2010-02-01

95

English Usage in Hong Kong.  

ERIC Educational Resources Information Center

Articles contained in this special issue on language usage in Hong Kong, particularly in the context of elementary and secondary education, include: "A Comparison of English Errors Made by Hong Kong Students and Those Made by Non-Native Learners of English Internationally" (David Bunton); "Errors in Guides to English Usage for Hong Kong Students"…

Bunton, David, Ed.; Green, Christopher F., Ed.

1991-01-01

96

A Comparison of the Usage of Tablet PC, Lecture Capture, and Online Homework in an Introductory Chemistry Course  

ERIC Educational Resources Information Center

Three emerging technologies were used in a large introductory chemistry class: a tablet PC, a lecture capture and replay software program, and an online homework program. At the end of the semester, student usage of the lecture replay and online homework systems was compared to course performance as measured by course grade and by a standardized…

Revell, Kevin D.

2014-01-01

97

A Comparison of the Influence of Social Factors and Technological Factors on Adoption and Usage of Knowledge Management Systems  

Microsoft Academic Search

Knowledge management strives for effective capture and application of organizational knowledge, a valuable resource imperative in sustaining an organization. In an effort to better achieve knowledge management initiatives, consideration of factors influencing adoption and usage of knowledge management systems are of great interest. Implementation of technological solutions are often considered organizational innovations subject to potential problems of resistance deeming social

Andrea J. Hester

2010-01-01

98

Differences in codon bias cannot explain differences in translational power among microbes  

PubMed Central

Background Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level and degree of codon bias among genes of Escherichia coli and other bacteria capable of rapid growth is commonly attributed to selection for high translational power. Conversely, the absence of such a correlation in some slowly growing microbes has been interpreted as the absence of selection for translational power. Because codon bias caused by translational selection varies between rapidly growing and slowly growing microbes, we investigated whether observed differences in translational power among microbes could be explained entirely by differences in the degree of codon bias. Although the data are not available to estimate the effect of codon bias in other species, we developed an empirically-based mathematical model to compare the translation rate of E. coli to the translation rate of a hypothetical strain which differs from E. coli only by lacking codon bias. Results Our reanalysis of data from the scientific literature suggests that translational power can differ by a factor of 5 or more between E. coli and slowly growing microbial species. Using empirical codon-specific in vivo translation rates for 29 codons, and several scenarios for extrapolating from these data to estimates over all codons, we find that codon bias cannot account for more than a doubling of the translation rate in E. coli, even with unrealistic simplifying assumptions that exaggerate the effect of codon bias. With more realistic assumptions, our best estimate is that codon bias accelerates translation in E. coli by no more than 60% in comparison to microbes with very little codon bias. Conclusions While codon bias confers a substantial benefit of faster translation and hence greater translational power, the magnitude of this effect is insufficient to explain observed differences in translational power among bacterial and archaeal species, particularly the differences between slowly growing and rapidly growing species. Hence, large differences in translational power suggest that the translational apparatus itself differs among microbes in ways that influence translational performance. PMID:15636642

Dethlefsen, Les; Schmidt, Thomas M

2005-01-01

99

Understanding continued information technology usage behavior: A comparison of three models in the context of mobile internet  

Microsoft Academic Search

This study examines the utility of three prospective models for understanding the continued IT usage behavior. The three models include: Expectation-Confirmation Model in IT Domain (ECM-IT), Technology Acceptance Model (TAM), and a hybrid model integrating TAM and ECM-IT (extended ECM-IT). Based on a survey of 1826 mobile Internet users, the LISREL analysis shows that all three models meet the various

Se-joon Hong; James Y. L. Thong; Kar Yan Tam

2006-01-01

100

A study of the purine/pyrimidine codon occurrence with a reduced centered variable and an evaluation compared to the frequency statistic.  

PubMed

With the three-letter alphabet [R,Y,N] (R = purine, Y = pyrimidine, N = R or Y), there are 26 codons (NNN being excluded): RNN,...,NNY (six codons at two unspecified bases N), RRN,...,NYY (12 codons at one unspecified base N), RRR,...,YYY (eight specified codons). A statistical methodology that uses the codon frequency and a reduced centered variable leads to similar results for a codon occurrence study, regardless of gene function and regardless of a particular protein coding gene taxonomic population. Therefore, this variable can be considered a new codon usage index, whose use removes certain nonsignificant results found with the frequency statistic. This methodology identifies the common and rare codons (i.e., the codons having the highest and lowest occurrence) and leads to a model of codon evolution at three successive states: RNN, then RNY, and finally RYY. Some biological relations between this model and the YRY(N)6YRY preferential occurrence are also presented. PMID:2520209

Michel, C J

1989-12-01

101

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

PubMed Central

Background The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values. Results The E-CAI server, available at , is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ) section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue) and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated. Conclusion The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences. PMID:18230160

Puigbo, Pere; Bravo, Ignacio G; Garcia-Vallve, Santiago

2008-01-01

102

A condition-specific codon optimization approach for improved heterologous gene expression in Saccharomyces cerevisiae  

PubMed Central

Background Heterologous gene expression is an important tool for synthetic biology that enables metabolic engineering and the production of non-natural biologics in a variety of host organisms. The translational efficiency of heterologous genes can often be improved by optimizing synonymous codon usage to better match the host organism. However, traditional approaches for optimization neglect to take into account many factors known to influence synonymous codon distributions. Results Here we define an alternative approach for codon optimization that utilizes systems level information and codon context for the condition under which heterologous genes are being expressed. Furthermore, we utilize a probabilistic algorithm to generate multiple variants of a given gene. We demonstrate improved translational efficiency using this condition-specific codon optimization approach with two heterologous genes, the fluorescent protein-encoding eGFP and the catechol 1,2-dioxygenase gene CatA, expressed in S. cerevisiae. For the latter case, optimization for stationary phase production resulted in nearly 2.9-fold improvements over commercial gene optimization algorithms. Conclusions Codon optimization is now often a standard tool for protein expression, and while a variety of tools and approaches have been developed, they do not guarantee improved performance for all hosts of applications. Here, we suggest an alternative method for condition-specific codon optimization and demonstrate its utility in Saccharomyces cerevisiae as a proof of concept. However, this technique should be applicable to any organism for which gene expression data can be generated and is thus of potential interest for a variety of applications in metabolic and cellular engineering. PMID:24636000

2014-01-01

103

Stop codon recognition in ciliates: Euplotes release factor does not respond to reassigned UGA codon  

PubMed Central

In eukaryotes, the polypeptide release factor 1 (eRF1) is involved in translation termination at all three stop codons. However, the mechanism for decoding stop codons remains unknown. A direct interaction of eRF1 with the stop codons has been postulated. Recent studies focus on eRF1 from ciliates in which some stop codons are reassigned to sense codons. Using an in vitro assay based on mammalian ribosomes, we show that eRF1 from the ciliate Euplotes aediculatus responds to UAA and UAG as stop codons and lacks the capacity to decipher the UGA codon, which encodes cysteine in this organism. This result strongly suggests that in ciliates with variant genetic codes eRF1 does not recognize the reassigned codons. Recent hypotheses describing stop codon discrimination by eRF1 are not fully consistent with the set of eRF1 sequences available so far and require direct experimental testing. PMID:11463747

Kervestin, Stephanie; Frolova, Ludmila; Kisselev, Lev; Jean-Jean, Olivier

2001-01-01

104

Comparison of Amino Acids Physico-Chemical Properties and Usage of Late Embryogenesis Abundant Proteins, Hydrophilins and WHy Domain  

PubMed Central

Late Embryogenesis Abundant proteins (LEAPs) comprise several diverse protein families and are mostly involved in stress tolerance. Most of LEAPs are intrinsically disordered and thus poorly functionally characterized. LEAPs have been classified and a large number of their physico-chemical properties have been statistically analyzed. LEAPs were previously proposed to be a subset of a very wide family of proteins called hydrophilins, while a domain called WHy (Water stress and Hypersensitive response) was found in LEAP class 8 (according to our previous classification). Since little is known about hydrophilins and WHy domain, the cross-analysis of their amino acids physico-chemical properties and amino acids usage together with those of LEAPs helps to describe some of their structural features and to make hypothesis about their function. Physico-chemical properties of hydrophilins and WHy domain strongly suggest their role in dehydration tolerance, probably by interacting with water and small polar molecules. The computational analysis reveals that LEAP class 8 and hydrophilins are distinct protein families and that not all LEAPs are a protein subset of hydrophilins family as proposed earlier. Hydrophilins seem related to LEAP class 2 (also called dehydrins) and to Heat Shock Proteins 12 (HSP12). Hydrophilins are likely unstructured proteins while WHy domain is structured. LEAP class 2, hydrophilins and WHy domain are thus proposed to share a common physiological role by interacting with water or other polar/charged small molecules, hence contributing to dehydration tolerance. PMID:25296175

Jaspard, Emmanuel; Hunault, Gilles

2014-01-01

105

Comparison of Oral Language Usage Among English Language Learners Diagnosed With a Learning Disability and Those in General Education  

Microsoft Academic Search

The investigator compared the linguistic characteristics of Spanish and English language samples taken from English language learners (ELLs) diagnosed with an academic learning disability (LD) and ELLs in general education to determine if the errors and characteristics of their language use differ. There was a statistically significant difference in the morphological error ratios of the English language samples when comparisons

Lisa Pray

2009-01-01

106

Assessment of work-integrated learning: comparison of the usage of a grading rubric by supervising radiographers and teachers  

PubMed Central

IntroductionProfessional work-integrated learning (WIL) that integrates the academic experience with off-campus professional experience placements is an integral part of many tertiary courses. Issues with the reliability and validity of assessment grades in these placements suggest that there is a need to strengthen the level of academic rigour of placements in these programmes. This study aims to compare the attitudes to the usage of assessment rubrics of radiographers supervising medical imaging students and teachers supervising pre-service teachers. MethodsWIL placement assessment practices in two programmes, pre-service teacher training (Avondale College of Higher Education, NSW) and medical diagnostic radiography (Faculty of Health Sciences, University of Sydney, NSW), were compared with a view to comparing assessment strategies across these two different educational domains. Educators (course coordinators) responsible for teaching professional development placements of teacher trainees and diagnostic radiography students developed a standards-based grading rubric designed to guide assessment of students’ work during WIL placement by assessors. After ?12 months of implementation of the rubrics, assessors’ reaction to the effectiveness and usefulness of the grading rubric was determined using a specially created survey form. Data were collected over the period from March to June 2011. Quantitative and qualitative data found that assessors in both programmes considered the grading rubric to be a vital tool in the assessment process, though teacher supervisors were more positive about the benefits of its use than the radiographer supervisors. ResultsBenefits of the grading rubric included accuracy and consistency of grading, ability to identify specific areas of desired development and facilitation of the provision of supervisor feedback. The use of assessment grading rubrics is of benefit to assessors in WIL placements from two very different teaching programmes. ConclusionRadiographers appear to need more training in the rubric's use, whereas teachers are found to generally use it appropriately. There are implications drawn from this finding that are applicable to health science and medical education in general.

Kilgour, Andrew J; Kilgour, Peter W; Gerzina, Tania; Christian, Beverly

2014-01-01

107

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

PubMed Central

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

Castro-Chavez, Fernando

2011-01-01

108

Ancestral Inference and the Study of Codon Bias Evolution: Implications for Molecular Evolutionary Analyses of the Drosophila melanogaster Subgroup  

PubMed Central

Reliable inference of ancestral sequences can be critical to identifying both patterns and causes of molecular evolution. Robustness of ancestral inference is often assumed among closely related species, but tests of this assumption have been limited. Here, we examine the performance of inference methods for data simulated under scenarios of codon bias evolution within the Drosophila melanogaster subgroup. Genome sequence data for multiple, closely related species within this subgroup make it an important system for studying molecular evolutionary genetics. The effects of asymmetric and lineage-specific substitution rates (i.e., varying levels of codon usage bias and departures from equilibrium) on the reliability of ancestral codon usage was investigated. Maximum parsimony inference, which has been widely employed in analyses of Drosophila codon bias evolution, was compared to an approach that attempts to account for uncertainty in ancestral inference by weighting ancestral reconstructions by their posterior probabilities. The latter approach employs maximum likelihood estimation of rate and base composition parameters. For equilibrium and most non-equilibrium scenarios that were investigated, the probabilistic method appears to generate reliable ancestral codon bias inferences for molecular evolutionary studies within the D. melanogaster subgroup. These reconstructions are more reliable than parsimony inference, especially when codon usage is strongly skewed. However, inference biases are considerable for both methods under particular departures from stationarity (i.e., when adaptive evolution is prevalent). Reliability of inference can be sensitive to branch lengths, asymmetry in substitution rates, and the locations and nature of lineage-specific processes within a gene tree. Inference reliability, even among closely related species, can be strongly affected by (potentially unknown) patterns of molecular evolution in lineages ancestral to those of interest. PMID:17957249

Akashi, Hiroshi; Goel, Piyush; John, Anoop

2007-01-01

109

The Effects of Codon Context on In Vivo Translation Speed  

PubMed Central

We developed a bacterial genetic system based on translation of the his operon leader peptide gene to determine the relative speed at which the ribosome reads single or multiple codons in vivo. Low frequency effects of so-called “silent” codon changes and codon neighbor (context) effects could be measured using this assay. An advantage of this system is that translation speed is unaffected by the primary sequence of the His leader peptide. We show that the apparent speed at which ribosomes translate synonymous codons can vary substantially even for synonymous codons read by the same tRNA species. Assaying translation through codon pairs for the 5?- and 3?- side positioning of the 64 codons relative to a specific codon revealed that the codon-pair orientation significantly affected in vivo translation speed. Codon pairs with rare arginine codons and successive proline codons were among the slowest codon pairs translated in vivo. This system allowed us to determine the effects of different factors on in vivo translation speed including Shine-Dalgarno sequence, rate of dipeptide bond formation, codon context, and charged tRNA levels. PMID:24901308

Chevance, Fabienne F. V.; Le Guyon, Soazig; Hughes, Kelly T.

2014-01-01

110

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

PubMed

We examine the standard genetic code with three stop codons. Assuming that the synchronization period of length 3 in DNA or RNA is violated during the transcription or translation processes, the probability of reading a frameshifted stop codon is higher than if the code would have only one stop codon. Consequently, the synthesis of RNA or proteins will soon terminate. In this way, cells do not produce undesirable proteins and essentially save energy. This hypothesis is tested on the AT-rich Drosophila genome, where the detection of frameshifted stop codons is even higher than the theoretical value. Using the binomial theorem, we establish the probability of reading a frameshifted stop codon within n steps. Since the genetic code is largely redundant, there is still space for some hidden secondary functions of this code. In particular, because stop codons do not contain cytosine, random C ? U and C ? T mutations in the third position of codons increase the number of hidden frameshifted stops and simultaneously the same amino acids are coded. This evolutionary advantage is demonstrated on the genomes of several simple species, e.g. Escherichia coli. PMID:22483666

K?ížek, Michal; K?ížek, Pavel

2012-07-01

111

Comparison of the clinical and preclinical biocompatibility testing of dental materials: are the ISO usage tests meaningful?  

PubMed

International Organization for Standardization (ISO 10993 and 7405) guidelines recommends the preclinical screening of dental materials using non-human primates. The literature contains no comparisons of responses to dental materials. To test the accuracy of preclinical screening tests for predicting human clinical responses, 106 class V pulp exposed cavities were prepared in human and non-human primate teeth. Teeth were restored with calcium hydroxide and amalgam, zinc oxide eugenol or resin-modified glass ionomer. Teeth were extracted after 10-163 days and prepared for histological analysis. Pulp cell numbers were compared and their reactionary dentin activity measured in response to cavity preparation. Pulp inflammatory activity was categorized according to ISO standards. There were no statistically significant differences between human and non-human primate teeth in terms of pulp reactions to dental materials. The use of non-human primates for preclinical biocompatibility investigation provided an accurate method of evaluating clinical responses to dental materials. PMID:17109428

Murray, Peter E; Garcia-Godoy, Franklin

2007-04-01

112

Codon populations in single-stranded whole human genome DNA Are fractal and fine-tuned by the Golden Ratio 1.618.  

PubMed

This new bioinformatics research bridges Genomics and Mathematics. We propose a universal "Fractal Genome Code Law": The frequency of each of the 64 codons across the entire human genome is controlled by the codon's position in the Universal Genetic Code table. We analyze the frequency of distribution of the 64 codons (codon usage) within single-stranded DNA sequences. Concatenating 24 Human chromosomes, we show that the entire human genome employs the well known universal genetic code table as a macro structural model. The position of each codon within this table precisely dictates its population. So the Universal Genetic Code Table not only maps codons to amino acids, but serves as a global checksum matrix. Frequencies of the 64 codons in the whole human genome scale are a self-similar fractal expansion of the universal genetic code. The original genetic code kernel governs not only the micro scale but the macro scale as well. Particularly, the 6 folding steps of codon populations modeled by the binary divisions of the "Dragon fractal paper folding curve" show evidence of 2 attractors. The numerical relationship between the attractors is derived from the Golden Ratio. We demonstrate that: (i) The whole Human Genome Structure uses the Universal Genetic Code Table as a tuning model. It predetermines global codons proportions and populations. The Universal Genetic Code Table governs both micro and macro behavior of the genome. (ii) We extend the Chargaff's second rule from the domain of single TCAG nucleotides to the larger domain of codon triplets. (iii) Codon frequencies in the human genome are clustered around 2 fractal-like attractors, strongly linked to the golden ratio 1.618. PMID:20658335

Perez, Jean-Claude

2010-09-01

113

Selection on GGU and CGU codons in the high expression genes in bacteria.  

PubMed

The fourfold degenerate site (FDS) in coding sequences is important for studying the effect of any selection pressure on codon usage bias (CUB) because nucleotide substitution per se is not under any such pressure at the site due to the unaltered amino acid sequence in a protein. We estimated the frequency variation of nucleotides at the FDS across the eight family boxes (FBs) defined as Um(g), the unevenness measure of a gene g. The study was made in 545 species of bacteria. In many bacteria, the Um(g) correlated strongly with Nc'-a measure of the CUB. Analysis of the strongly correlated bacteria revealed that the U-ending codons (GGU, CGU) were preferred to the G-ending codons (GGG, CGG) in Gly and Arg FBs even in the genomes with G+C % higher than 65.0. Further evidence suggested that these codons can be used as a good indicator of selection pressure on CUB in genomes with higher G+C %. PMID:24271854

Satapathy, Siddhartha Sankar; Powdel, Bhesh Raj; Dutta, Malay; Buragohain, Alak Kumar; Ray, Suvendra Kumar

2014-01-01

114

Two-codon T-box riboswitch binding two tRNAs  

PubMed Central

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

Saad, Nizar Y.; Stamatopoulou, Vassiliki; Braye, Melanie; Drainas, Denis; Stathopoulos, Constantinos; Becker, Hubert Dominique

2013-01-01

115

A common periodic table of codons and amino acids  

Microsoft Academic Search

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

J. C. Biro; B. Benyo; C. Sansom; Á Szlávecz; G Fördös; T Micsik; Z Benyó

2003-01-01

116

Usage Guide September 2011  

E-print Network

HRMS Action Reason Usage Guide September 2011 #12;HRMS Action Reason Usage Guide Office that require at least one job row to be set up: courtesy appts., emeritus appts., nonpaid visiting appts Usage Guide Office of Human Resources Action Action Definition Reason When to Use NEE or EE? Affiliated

Subramanian, Venkat

117

Model Checking Usage Policies  

Microsoft Academic Search

We propose a model for specifying, analysing and enforc- ing safe usage of resources. Our usage policies allow for parametricity over resources, and they can be enforced through finite state automata. The patterns of resource access and creation are described through a basic calculus of usages. In spite of the augmented flexibility given by resource creation and by policy parametrization,

Massimo Bartoletti; Pierpaolo Degano; Gian Luigi Ferrari; Roberto Zunino

2008-01-01

118

Exploring iPhone Usage: The Influence of Socioeconomic Differences on Smartphone Adoption, Usage and Usability  

E-print Network

Exploring iPhone Usage: The Influence of Socioeconomic Differences on Smartphone Adoption, Usage applications are installed and used. We present a longitudinal study of 34 iPhone 3GS users. 24 perceived the usability of their iPhones poorly in comparison to the other groups. We further discuss

Zhong, Lin

119

Codon usage variability determines the correlation between proteome and transcriptome fold changes  

Microsoft Academic Search

Background  The availability of high throughput experimental methods has made possible to observe the relationships between proteome and\\u000a transcirptome. The protein abundances show a positive but weak correlation with the concentrations of their cognate mRNAs.\\u000a This weak correlation implies that there are other crucial effects involved in the regulation of protein translation, different\\u000a from the sole availability of mRNA. It is

Roberto Olivares-Hernández; Sergio Bordel; Jens Nielsen

2011-01-01

120

A meta-analysis of single base-pair substitutions in translational termination codons ('nonstop' mutations) that cause human inherited disease  

PubMed Central

'Nonstop' mutations are single base-pair substitutions that occur within translational termination (stop) codons and which can lead to the continued and inappropriate translation of the mRNA into the 3'-untranslated region. We have performed a meta-analysis of the 119 nonstop mutations (in 87 different genes) known to cause human inherited disease, examining the sequence context of the mutated stop codons and the average distance to the next alternative in-frame stop codon downstream, in comparison with their counterparts from control (non-mutated) gene sequences. A paucity of alternative in-frame stop codons was noted in the immediate vicinity (0-49 nucleotides downstream) of the mutated stop codons as compared with their control counterparts (p = 7.81 × 10-4). This implies that at least some nonstop mutations with alternative stop codons in close proximity will not have come to clinical attention, possibly because they will have given rise to stable mRNAs (not subject to nonstop mRNA decay) that are translatable into proteins of near-normal length and biological function. A significant excess of downstream in-frame stop codons was, however, noted in the range 150-199 nucleotides from the mutated stop codon (p = 8.55 × 10-4). We speculate that recruitment of an alternative stop codon at greater distance from the mutated stop codon may trigger nonstop mRNA decay, thereby decreasing the amount of protein product and yielding a readily discernible clinical phenotype. Confirmation or otherwise of this postulate must await the emergence of a clearer understanding of the mechanism of nonstop mRNA decay in mammalian cells. PMID:21712188

2011-01-01

121

Readthrough strategies for stop codons in Duchenne muscular dystrophy  

Microsoft Academic Search

Duchenne muscular dystrophy is due to mutations of the dystrophin gene. These are large deletions or duplications in 80% of cases, while premature stop codons (nonsense point mutations) account for 7% of cases. This subgroup of patients may take advantage of the properties of the antibi- otic gentamicin to suppress stop codons (readthrough). The efficiency of the readthrough varies inversely

S. AURINO; V. N IGRO

122

AGRICULTURAL CHEMICAL USAGE DATA  

EPA Science Inventory

This report, which summarizes the use of agricultural chemicals is issued by the National Agricultural Statistics Service (NASS) as part of its series on Agricultural Chemical Usage. Other publications in the series present statistics for on-farm agricultural chemical usage for f...

123

Analysis of the use of codon pairs in the HE gene of the ISA virus shows a correlation between bias in HPR codon-pair use and mortality rates caused by the virus  

PubMed Central

Background Segment 6 of the ISA virus codes for hemoagglutinin-esterase (HE). This segment is highly variable, with more than 26 variants identified. The major variation is observed in what is called the high polymorphism region (HPR). The role of the different HPR zones in the viral cycle or evolution remains unknown. However viruses that present the HPR0 are avirulent, while viruses with important deletions in this region have been responsible for outbreaks with high mortality rates. In this work, using bioinformatic tools, we examined the influence of different HPRs on the adaptation of HE genes to the host translational machinery and the relationship to observed virulence. Methods Translational efficiency of HE genes and their HPR were estimated analyzing codon-pair bias (CPB), adaptation to host codon use (codon adaptation index - CAI) and the adaptation to available tRNAs (tAI). These values were correlated with reported mortality for the respective ISA virus and the ?G of RNA folding. tRNA abundance was inferred from tRNA gene numbers identified in the Salmo salar genome using tRNAScan-SE. Statistical correlation between data was performed using a non-parametric test. Results We found that HPR0 contains zones with codon pairs of low frequency and low availability of tRNA with respect to salmon codon-pair usage, suggesting that HPR modifies HE translational efficiency. Although calculating tAI was impossible because one third of tRNAs (~60.000) were tRNA-ala, translational efficiency measured by CPB shows that as HPR size increases, the CPB value of the HE gene decreases (P = 2x10-7, ? = ?0.675, n = 63) and that these values correlate positively with the mortality rates caused by the virus (? = 0.829, P = 2x10-7, n = 11). The mortality associated with different virus isolates or their corresponding HPR sizes were not related with the ?G of HPR RNA folding, suggesting that the secondary structure of HPR RNA does not modify virulence. Conclusions Our results suggest that HPR size affects the efficiency of gene translation, which modulates the virulence of the virus by a mechanism similar to that observed in production of live attenuated vaccines through deoptimization of codon-pair usage. PMID:23742749

2013-01-01

124

Heterologous Stop Codon Readthrough of Metazoan Readthrough Candidates in Yeast  

E-print Network

Recent analysis of genomic signatures in mammals, flies, and worms indicates that functional translational stop codon readthrough is considerably more abundant in metazoa than previously recognized, but this analysis ...

Jungreis, Irwin

125

Evidence of efficient stop codon readthrough in four mammalian genes  

E-print Network

Stop codon readthrough is used extensively by viruses to expand their gene expression. Until recent discoveries in Drosophila, only a very limited number of readthrough cases in chromosomal genes had been reported. Analysis ...

Loughran, Gary

126

Adaptation to Different Human Populations by HIV-1 Revealed by Codon-Based Analyses  

PubMed Central

Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations. PMID:16789820

Kosakovsky Pond, Sergei L; Frost, Simon D. W; Grossman, Zehava; Gravenor, Michael B; Richman, Douglas D; Brown, Andrew J. Leigh

2006-01-01

127

Properties and determinants of codon decoding time distributions  

PubMed Central

Background Codon decoding time is a fundamental property of mRNA translation believed to affect the abundance, function, and properties of proteins. Recently, a novel experimental technology--ribosome profiling--was developed to measure the density, and thus the speed, of ribosomes at codon resolution. Specifically, this method is based on next-generation sequencing, which theoretically can provide footprint counts that correspond to the probability of observing a ribosome in this position for each nucleotide in each transcript. Results In this study, we report for the first time various novel properties of the distribution of codon footprint counts in five organisms, based on large-scale analysis of ribosomal profiling data. We show that codons have distinctive footprint count distributions. These tend to be preserved along the inner part of the ORF, but differ at the 5' and 3' ends of the ORF, suggesting that the translation-elongation stage actually includes three biophysical sub-steps. In addition, we study various basic properties of the codon footprint count distributions and show that some of them correlate with the abundance of the tRNA molecule types recognizing them. Conclusions Our approach emphasizes the advantages of analyzing ribosome profiling and similar types of data via a comparative genomic codon-distribution-centric view. Thus, our methods can be used in future studies related to translation and even transcription elongation.

2014-01-01

128

Mutations that convert the four leucine codons of the Salmonella typhimurium leu leader to four threonine codons.  

PubMed Central

In Salmonella typhimurium, expression of the leucine operon is regulated by a transcription attenuation mechanism. According to a current model of attenuation, elevated expression of this operon requires that a ribosome stall at one of four adjacent codons for leucine on a leader RNA. We used oligonucleotide-directed mutagenesis to convert the four leucine codons of the S. typhimurium leu leader to four threonine codons. Analysis of the resulting mutant operon showed that almost all regulation by leucine had been abolished. The mutant operon was, instead, partially derepressed by a limitation for charged threonine tRNA. These results provide direct evidence for the function for the four leucine codons postulated by the attenuator model. An unexpected observation made during these studies was that the wild-type leu operon was partially derepressed by starvation for threonine. PMID:3922957

Carter, P W; Weiss, D L; Weith, H L; Calvo, J M

1985-01-01

129

Dual Accelerometer Usage Strategy for Onboard Space Navigation  

NASA Technical Reports Server (NTRS)

This work introduces a dual accelerometer usage strategy for onboard space navigation. In the proposed algorithm the accelerometer is used to propagate the state when its value exceeds a threshold and it is used to estimate its errors otherwise. Numerical examples and comparison to other accelerometer usage schemes are presented to validate the proposed approach.

Zanetti, Renato; D'Souza, Chris

2012-01-01

130

Natural selection retains overrepresented out-of-frame stop codons against frameshift peptides in prokaryotes  

PubMed Central

Background Out-of-frame stop codons (OSCs) occur naturally in coding sequences of all organisms, providing a mechanism of early termination of translation in incorrect reading frame so that the metabolic cost associated with frameshift events can be reduced. Given such a functional significance, we expect statistically overrepresented OSCs in coding sequences as a result of a widespread selection. Accordingly, we examined available prokaryotic genomes to look for evidence of this selection. Results The complete genome sequences of 990 prokaryotes were obtained from NCBI GenBank. We found that low G+C content coding sequences contain significantly more OSCs and G+C content at specific codon positions were the principal determinants of OSC usage bias in the different reading frames. To investigate if there is overrepresentation of OSCs, we modeled the trinucleotide and hexanucleotide biases of the coding sequences using Markov models, and calculated the expected OSC frequencies for each organism using a Monte Carlo approach. More than 93% of 342 phylogenetically representative prokaryotic genomes contain excess OSCs. Interestingly the degree of OSC overrepresentation correlates positively with G+C content, which may represent a compensatory mechanism for the negative correlation of OSC frequency with G+C content. We extended the analysis using additional compositional bias models and showed that lower-order bias like codon usage and dipeptide bias could not explain the OSC overrepresentation. The degree of OSC overrepresentation was found to correlate negatively with the optimal growth temperature of the organism after correcting for the G+C% and AT skew of the coding sequence. Conclusions The present study uses approaches with statistical rigor to show that OSC overrepresentation is a widespread phenomenon among prokaryotes. Our results support the hypothesis that OSCs carry functional significance and have been selected in the course of genome evolution to act against unintended frameshift occurrences. Some results also hint that OSC overrepresentation being a compensatory mechanism to make up for the decrease in OSCs in high G+C organisms, thus revealing the interplay between two different determinants of OSC frequency. PMID:20828396

2010-01-01

131

The association of p53 mutations and p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms with breast cancer in Northern Greece  

Microsoft Academic Search

The aim of this study was to explore a possible association between p53 codon 72, Her 2 codon 655 and MTHFR C677T polymorphisms and breast cancer in Northern Greece. We examined 42 women with breast cancer and 51 controls. A total of 42 women with breast cancer as well as healthy controls were investigated and results showed that p53 codon

Theodora G. Kalemi; Alexandros F. Lambropoulos; Maria Gueorguiev; Sofia Chrisafi; Konstantinos T. Papazisis; Alexandros Kotsis

2005-01-01

132

Codon Preference Optimization Increases Prokaryotic Cystatin C Expression  

PubMed Central

Gene expression is closely related to optimal vector-host system pairing in many prokaryotes. Redesign of the human cystatin C (cysC) gene using the preferred codons of the prokaryotic system may significantly increase cysC expression in Escherichia coli (E. coli). Specifically, cysC expression may be increased by removing unstable sequences and optimizing GC content. According to E. coli expression system codon preferences, the gene sequence was optimized while the amino acid sequence was maintained. The codon-optimized cysC (co-cysC) and wild-type cysC (wt-cysC) were expressed by cloning the genes into a pET-30a plasmid, thus transforming the recombinant plasmid into E. coli BL21. Before and after the optimization process, the prokaryotic expression vector and host bacteria were examined for protein expression and biological activation of CysC. The recombinant proteins in the lysate of the transformed bacteria were purified using Ni2+-NTA resin. Recombinant protein expression increased from 10% to 46% based on total protein expression after codon optimization. Recombinant CysC purity was above 95%. The significant increase in cysC expression in E. coli expression produced by codon optimization techniques may be applicable to commercial production systems. PMID:23093857

Wang, Qing; Mei, Cui; Zhen, Honghua; Zhu, Jess

2012-01-01

133

Diversity in smartphone usage  

Microsoft Academic Search

Using detailed traces from 255 users, we con- duct a comprehensive study of smartphone use. We char- acterize intentional user activities - interactions with the device and the applications used - and the impact of those activities on network and energy usage. We find immense diversity among users. Along all aspects that we study, users differ by one or more

Hossein Falaki; Ratul Mahajan; Srikanth Kandula; Dimitrios Lymberopoulos; Ramesh Govindan; Deborah Estrin

2010-01-01

134

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

NASA Astrophysics Data System (ADS)

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

Lind, Christoffer; Sund, Johan; Åqvist, Johan

2013-12-01

135

Gene Expression, Amino Acid Conservation, and Hydrophobicity Are the Main Factors Shaping Codon Preferences in Mycobacterium tuberculosis and Mycobacterium leprae  

Microsoft Academic Search

.  \\u000a \\u000a Mycobacterium tuberculosis and Mycobacterium leprae are the ethiological agents of tuberculosis and leprosy, respectively. After performing extensive comparisons between genes\\u000a from these two GC-rich bacterial species, we were able to construct a set of 275 homologous genes. Since these two bacterial\\u000a species also have a very low growth rate, translational selection could not be so determinant in their codon

Antonio B. de Miranda; Fernando Alvarez-Valin; Kamel Jabbari; Wim M. Degrave; Giorgio Bernardi

2000-01-01

136

Forecasting Computer Usage  

NSDL National Science Digital Library

This article, created by Julie M. Hays of the University of St. Thomas, presents a dataset containing actual monthly data on computer usage in Best Buy stores from August 1996 to July 2000. This dataset can be used to illustrate time-series forecasting, causal forecasting, simple linear regression, unequal error variances, and variable transformation. Other key concepts include model-building and seasonal variation. This is a nice lesson as it uses real world data and applies it to basic statistical theory.

Hays, Julie M.

2009-02-12

137

Insights & Perspectives Quadruplet codons: One small step for a  

E-print Network

for proteins An expanded genetic code could address fundamental questions about algorithmic information quadruplet codons, paving the way for studies on fundamental ques- tions about the origin of the genetic code to an infinitesimal fraction of the total volume, a full quadruplet genetic code would essentially double the infor

Chen, Irene

138

All-codon scanning identifies p53 cancer rescue mutations  

E-print Network

,2 , Linda V. Hall1 , Kirsty Salmon1 , G. Wesley Hatfield1,3,4 , Richard H. Lathrop1,2,5, * and Peter Kaiser6 of Microbiology and Molecular Genetics, 4 Department of Chemical Engineering and Materials Science, 5 Department with modified properties. We describe the fast and simple All- Codon Scanning (ACS) strategy that creates

Lathrop, Richard H.

139

An evaluation of data-driven motion estimation in comparison to the usage of external-surrogates in cardiac SPECT imaging  

NASA Astrophysics Data System (ADS)

Motion estimation methods in single photon emission computed tomography (SPECT) can be classified into methods which depend on just the emission data (data-driven), or those that use some other source of information such as an external surrogate. The surrogate-based methods estimate the motion exhibited externally which may not correlate exactly with the movement of organs inside the body. The accuracy of data-driven strategies on the other hand is affected by the type and timing of motion occurrence during acquisition, the source distribution, and various degrading factors such as attenuation, scatter, and system spatial resolution. The goal of this paper is to investigate the performance of two data-driven motion estimation schemes based on the rigid-body registration of projections of motion-transformed source distributions to the acquired projection data for cardiac SPECT studies. Comparison is also made of six intensity based registration metrics to an external surrogate-based method. In the data-driven schemes, a partially reconstructed heart is used as the initial source distribution. The partially-reconstructed heart has inaccuracies due to limited angle artifacts resulting from using only a part of the SPECT projections acquired while the patient maintained the same pose. The performance of different cost functions in quantifying consistency with the SPECT projection data in the data-driven schemes was compared for clinically realistic patient motion occurring as discrete pose changes, one or two times during acquisition. The six intensity-based metrics studied were mean-squared difference, mutual information, normalized mutual information (NMI), pattern intensity (PI), normalized cross-correlation and entropy of the difference. Quantitative and qualitative analysis of the performance is reported using Monte-Carlo simulations of a realistic heart phantom including degradation factors such as attenuation, scatter and system spatial resolution. Further the visual appearance of motion-corrected images using data-driven motion estimates was compared to that obtained using the external motion-tracking system in patient studies. Pattern intensity and normalized mutual information cost functions were observed to have the best performance in terms of lowest average position error and stability with degradation of image quality of the partial reconstruction in simulations. In all patients, the visual quality of PI-based estimation was either significantly better or comparable to NMI-based estimation. Best visual quality was obtained with PI-based estimation in one of the five patient studies, and with external-surrogate based correction in three out of five patients. In the remaining patient study there was little motion and all methods yielded similar visual image quality.

Mitra Mukherjee, Joyeeta; Hutton, Brian F.; Johnson, Karen L.; Hendrik Pretorius, P.; King, Michael A.

2013-11-01

140

Resolving Discrepancy between Nucleotides and Amino Acids in Deep-Level Arthropod Phylogenomics: Differentiating Serine Codons in 21-Amino-Acid Models  

E-print Network

to the prefix ‘‘http://zoobank.org/’’. The LSID for this publication is: urn:lsid:zoobank.org:pub:77C2B51C- F5DB-4FCA-A98E-9AAF7A70EA94. The electronic edition of this work was published in a journal with an ISSN, and has been archived and is available from...-distance trees tell a similar story (Figures S4, S5). The proportions of Ser1:Ser2 codons and S/Z residues have also been displayed for each of the 80 taxa (Figure S6). Again, there is substantial variation in codon usage but no striking correlation to taxonomic...

Zwick, Andreas; Regier, Jerome C.; Zwickl, Derrick J.

2012-11-20

141

Why Are Translationally Sub-Optimal Synonymous Codons Used in Escherichia coli?  

E-print Network

Why Are Translationally Sub-Optimal Synonymous Codons Used in Escherichia coli? Nick G.C. Smith selection favors certain synony- mous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persist. We use the frequency distributions of synonymous poly

Eyre-Walker, Adam

142

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

ERIC Educational Resources Information Center

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

Szeberenyi, Jozsef

2009-01-01

143

Notational usage modulates attention networks in binumerates.  

PubMed

Multicultural environments require learning multiple number notations wherein some are encountered more frequently than others. This leads to differences in exposure and consequently differences in usage between notations. We find that differential notational usage imposes a significant neurocognitive load on number processing. Despite simultaneous acquisition, twenty four adult binumerates, familiar with two positional writing systems namely Hindu Nagari digits and Hindu Arabic digits, reported significantly lower preference and usage for Nagari as compared to Arabic. Twenty-four participants showed significantly increased reaction times and reduced accuracy while performing magnitude comparison tasks in Nagari with respect to Arabic. Functional magnetic resonance imaging revealed that processing Nagari elicited significantly greater activity in number processing and attention networks. A direct subtraction of networks for Nagari and Arabic notations revealed a neural circuit comprising of bilateral Intra-parietal Sulcus (IPS), Inferior and Mid Frontal Gyri, Fusiform Gyrus and the Anterior Cingulate Cortex (FDR p < 0.005). Additionally, whole brain correlation analysis showed that activity in the left inferior parietal region was modulated by task performance in Nagari. We attribute the increased activation in Nagari to increased task difficulty due to infrequent exposure and usage. Our results reiterate the role of left IPS in modulating performance in numeric tasks and highlight the role of the attention network for monitoring symbolic notation mode in binumerates. PMID:24904366

Koul, Atesh; Tyagi, Vaibhav; Singh, Nandini C

2014-01-01

144

Notational usage modulates attention networks in binumerates  

PubMed Central

Multicultural environments require learning multiple number notations wherein some are encountered more frequently than others. This leads to differences in exposure and consequently differences in usage between notations. We find that differential notational usage imposes a significant neurocognitive load on number processing. Despite simultaneous acquisition, twenty four adult binumerates, familiar with two positional writing systems namely Hindu Nagari digits and Hindu Arabic digits, reported significantly lower preference and usage for Nagari as compared to Arabic. Twenty-four participants showed significantly increased reaction times and reduced accuracy while performing magnitude comparison tasks in Nagari with respect to Arabic. Functional magnetic resonance imaging revealed that processing Nagari elicited significantly greater activity in number processing and attention networks. A direct subtraction of networks for Nagari and Arabic notations revealed a neural circuit comprising of bilateral Intra-parietal Sulcus (IPS), Inferior and Mid Frontal Gyri, Fusiform Gyrus and the Anterior Cingulate Cortex (FDR p < 0.005). Additionally, whole brain correlation analysis showed that activity in the left inferior parietal region was modulated by task performance in Nagari. We attribute the increased activation in Nagari to increased task difficulty due to infrequent exposure and usage. Our results reiterate the role of left IPS in modulating performance in numeric tasks and highlight the role of the attention network for monitoring symbolic notation mode in binumerates. PMID:24904366

Koul, Atesh; Tyagi, Vaibhav; Singh, Nandini C.

2014-01-01

145

Resolving Discrepancy between Nucleotides and Amino Acids in Deep-Level Arthropod Phylogenomics: Differentiating Serine Codons in 21-Amino-Acid Models  

PubMed Central

Background In a previous study of higher-level arthropod phylogeny, analyses of nucleotide sequences from 62 protein-coding nuclear genes for 80 panarthopod species yielded significantly higher bootstrap support for selected nodes than did amino acids. This study investigates the cause of that discrepancy. Methodology/Principal Findings The hypothesis is tested that failure to distinguish the serine residues encoded by two disjunct clusters of codons (TCN, AGY) in amino acid analyses leads to this discrepancy. In one test, the two clusters of serine codons (Ser1, Ser2) are conceptually translated as separate amino acids. Analysis of the resulting 21-amino-acid data matrix shows striking increases in bootstrap support, in some cases matching that in nucleotide analyses. In a second approach, nucleotide and 20-amino-acid data sets are artificially altered through targeted deletions, modifications, and replacements, revealing the pivotal contributions of distinct Ser1 and Ser2 codons. We confirm that previous methods of coding nonsynonymous nucleotide change are robust and computationally efficient by introducing two new degeneracy coding methods. We demonstrate for degeneracy coding that neither compositional heterogeneity at the level of nucleotides nor codon usage bias between Ser1 and Ser2 clusters of codons (or their separately coded amino acids) is a major source of non-phylogenetic signal. Conclusions The incongruity in support between amino-acid and nucleotide analyses of the forementioned arthropod data set is resolved by showing that “standard” 20-amino-acid analyses yield lower node support specifically when serine provides crucial signal. Separate coding of Ser1 and Ser2 residues yields support commensurate with that found by degenerated nucleotides, without introducing phylogenetic artifacts. While exclusion of all serine data leads to reduced support for serine-sensitive nodes, these nodes are still recovered in the ML topology, indicating that the enhanced signal from Ser1 and Ser2 is not qualitatively different from that of the other amino acids. PMID:23185239

Zwick, Andreas; Regier, Jerome C.; Zwickl, Derrick J.

2012-01-01

146

Feasibility Study of a Rotorcraft Health and Usage Monitoring System (HUMS): Usage and Structural Life Monitoring Evaluation  

NASA Technical Reports Server (NTRS)

The objective of this study was to evaluate two techniques, Flight Condition Recognition (FCR) and Flight Load Synthesis (FIS), for usage monitoring and assess the potential benefits of extending the retirement intervals of life-limited components, thus reducing the operator's maintenance and replacement costs. Both techniques involve indirect determination of loads using measured flight parameters and subsequent fatigue analysis to calculate the life expended on the life-limited components. To assess the potential benefit of usage monitoring, the two usage techniques were compared to current methods of component retirement. In addition, comparisons were made with direct load measurements to assess the accuracy of the two techniques.

Dickson, B.; Cronkhite, J.; Bielefeld, S.; Killian, L.; Hayden, R.

1996-01-01

147

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

Microsoft Academic Search

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

Brian R. Morton

1993-01-01

148

Photograph Usage in History Education  

ERIC Educational Resources Information Center

In this study, the effect of photograph usage in history education to the students' achievement was tried to be identified. In the study which was done with a pre-test post-test control group design, a frame was tried to be established between the experimental group and the analytical usage of the photograph, the control group's courses were done…

Akbaba, Bulent

2009-01-01

149

Hepatitis A Virus Mutant Spectra under the Selective Pressure of Monoclonal Antibodies: Codon Usage Constraints Limit Capsid Variability  

Microsoft Academic Search

Severe structural constraints in the hepatitis A virus (HAV) capsid have been suggested as the reason for the lack of emergence of new serotypes in spite of the occurrence of complex distributions of mutants or quasi- species. Analysis of the HAV mutant spectra under immune pressure by the monoclonal antibodies (MAbs) K34C8 (immunodominant site) and H7C27 (glycophorin binding site) has

Lluõ ´ s Aragones; Albert Bosch; R. M. Pinto

2008-01-01

150

1999 Oxford University Press16421649 Nucleic Acids Research, 1999, Vol. 27, No. 7 Proteome composition and codon usage in  

E-print Network

and Treponema pallidum show strong strand-specific skews in nucleotide composition, with the leading strand spirochaete bacteria, Borrelia burgdorferi and Treponema pallidum, have been reported by Fraser and colleagues on the two strands, in both species. There are also substantial differences between the species, with T.pallidum

Paris-Sud XI, Université de

151

Lung cancer risk in relation to TP53 codon 47 and codon 72 polymorphism in Bangladeshi population.  

PubMed

The objective of this study was to determine whether p53 codon 47 and codon 72 polymorphisms are associated with increased risk of lung cancer in Bangladeshi population. We carried out a case-control study and examined the genotype distribution Pro47Ser and Arg72Pro single-nucleotide polymorphisms along with tobacco smoking in the predisposition of lung cancer by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The study included 106 lung cancer patients and 116 control subjects from Bangladesh. Lung cancer risk was estimated as odds ratio (OR) and 95 % confidence interval (CI) using conditional logistic regression models adjusting for age, sex, and smoking. No significant association was found between Pro47Ser SNP and lung cancer. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in lung cancer were 25.5, 37.7, and 36.8 %, respectively; frequencies in the controls were 53.4, 30.2, and 16.4 %, respectively (p?codon 72 genotype distributions. When classified by smoking status, the effects of Arg72Pro polymorphism on lung cancer risk was only found to be significant (? (2) ?=?33.94, p?=?0.00000004) in case of heavy smokers (40 packs per year or more). We conclude that not Pro47Ser SNP but Arg72Pro SNP is involved in susceptibility to developing lung cancer, at least in Bangladeshi population. PMID:25034526

Mostaid, Md Shaki; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Bin Sayeed, Muhammad Shahdaat; Hasnat, Abul

2014-10-01

152

Patterns of codon recognition by isoacceptor aminoacyl-tRNAs from wheat germ.  

PubMed Central

Isoacceptors of Ala-, Arg-, Glu-, Gln-, Ile-, Leu-, Lys-, Ser-, Thr- and Val-tRNAs from wheat germ have been resolved by reverse phast chromatography. Codon recognition properties have been determined on isolated fractions of each of these aa-tRNAs and codon assignments have been made to a number of isoacceptors. Evolutionary changes which have occurred in patterns of codon recognition by isoacceptor aa-tRNAs in wheat germ and other organisms are discussed. PMID:251931

Hatfield, D; Rice, M

1978-01-01

153

Premature Stop Codon in MMP20 Causing Amelogenesis Imperfecta  

PubMed Central

Proteolytic enzymes are necessary for the hardening of dental enamel during development, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal recessive amelogenesis imperfecta (ARAI). So far, only one KLK4 and two MMP20 mutations have been reported. We have identified an ARAI-causing point mutation (c.l02G>A, g.l02G>A, and p.W34X) in exon 1 of MMP20 in a proband with autosomal recessive hypoplastic-hypomaturation amelogenesis imperfecta. The G to A transition changes the tryptophan (W) codon (TGG) at amino acid position 34 into a translation termination (X) codon (TGA). No disease-causing sequence variations were detected in KLK4. The affected enamel is thin, with mild spacing in the anterior dentition. The enamel layer is hypomineralized, does not contrast with dentin on radiographs, and tends to chip away from the underlying dentin. An intrinsic yellowish pigmentation is evident even during eruption. The phenotype supports current ideas concerning the function of enamelysin. PMID:18096894

Papagerakis, P.; Lin, H-K.; Lee, K. Y.; Hu, Y.; Simmer, J. P.; Bartlett, J. D.; Hu, J. C-C

2009-01-01

154

Non-random base composition in codons of mitochondrial cytochrome b gene in vertebrates.  

PubMed

Cytochrome b is the central catalytic subunit of the quinol:cytochrome c oxidoreductase of complex III of the mitochondrial oxidative phosphorylation system and is essential to the viability of most eukaryotic cells. Partial cytochrome b gene sequences of 14 species representing mammals, birds, reptiles and amphibians are presented here including some species typical for Poland. For the analysed species a comparative analysis of the natural variation in the gene was performed. This information has been used to discuss some aspects of gene sequence - protein function relationships. Review of relevant literature indicates that similar comparisons have been made only for basic mammalian species. Moreover, there is little information about the Polish-specific species. We observed that there is a strong non-random distribution of nucleotides in the cytochrome b sequence in all tested species with the highest differences at the third codon position. This is also the codon position of the strongest compositional bias. Some tested species, representing distant systematic groups, showed unique base composition differing from the others. The quail, frog, python and elk prefer C over A in the light DNA strand. Species belonging to the artiodactyls stand out from the remaining ones and contain fewer pyrimidines. The observed overall rate of amino acid identity is about 61%. The region covering Q(o) center as well as histidines 82 and 96 (heme ligands) are totally conserved in all tested species. Additionally, the applied method and the sequences can also be used for diagnostic species identification by veterinary and conservation agencies. PMID:15625561

Prusak, Beata; Grzybowski, Tomasz

2004-01-01

155

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

SciTech Connect

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.

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

1996-04-01

156

Cognitive performance of patients with mesial temporal lobe epilepsy is not associated with human prion protein gene variant allele at codons 129 and 171.  

PubMed

Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common surgically remediable epileptic syndrome, has been associated with a cellular prion protein (PrPc) gene (Prnp) variant allele at codon 171. The polymorphism consisting of a methionine-for-valine substitution at codon 129 has been associated with early cognitive deterioration in elderly people and patients with Down syndrome. The same variant allele in homozygosis (V129V) has been associated to a lower long-term memory in healthy humans. PrPc mediates several processes related to neuroplasticity, and its role in cognitive processes remains unknown. In this study, we evaluated the genetic contribution of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive performance, measured with 19 neuropsychological tests, of patients with refractory MTLE-HS with the normal Prnp genotypes was compared with that of patients with the variant alleles at codons 129 and 171. With the effects of clinical, demographic, electrophysiological, and neuroimaging variable interactions controlled by multiple linear regression analysis and adjustment for multiple test comparisons, the presence of Prnp variant alleles was found not to be significantly associated to cognitive performance of patients with MTLE-HS. The presence of variant alleles at codons 129 and 171 is not associated to cognitive performance of patients with refractory MTLE-HS. PMID:16580884

Coimbra, Erica R; Rezek, Karinne; Escorsi-Rosset, Sara; Landemberger, Michele C; Castro, Rosa M R P S; Valadão, Michelle N; Guarnieri, Ricardo; Velasco, Tonicarlo R; Terra-Bustamante, Vera C; Bianchin, Marino M; Wichert-Ana, Lauro; Alexandre, Veriano; Brentani, Ricardo R; Martins, Vilma R; Sakamoto, Américo C; Walz, Roger

2006-05-01

157

Marijuana Usage and Hypnotic Susceptibility  

ERIC Educational Resources Information Center

Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

Franzini, Louis R.; McDonald, Roy D.

1973-01-01

158

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

SciTech Connect

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.

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

1993-10-01

159

The relationship between third-codon position nucleotide content, codon bias, mRNA secondary structure and gene expression in the drosophilid alcohol dehydrogenase genes Adh and Adhr.  

PubMed

To gain insights into the relationship between codon bias, mRNA secondary structure, third-codon position nucleotide distribution, and gene expression, we predicted secondary structures in two related drosophilid genes, Adh and Adhr, which differ in degree of codon bias and level of gene expression. Individual structural elements (helices) were inferred using the comparative method. For each gene, four types of randomization simulations were performed to maintain/remove codon bias and/or to maintain or alter third-codon position nucleotide composition (N3). In the weakly expressed, weakly biased gene Adhr, the potential for secondary structure formation was found to be much stronger than in the highly expressed, highly biased gene Adh. This is consistent with the observation of approximately equal G and C percentages in Adhr ( approximately 31% across species), whereas in Adh the N3 distribution is shifted toward C (42% across species). Perturbing the N3 distribution to approximately equal amounts of A, G, C, and T increases the potential for secondary structure formation in Adh, but decreases it in Adhr. On the other hand, simulations that reduce codon bias without changing N3 content indicate that codon bias per se has only a weak effect on the formation of secondary structures. These results suggest that, for these two drosophilid genes, secondary structure is a relatively independent, negative regulator of gene expression. Whereas the degree of codon bias is positively correlated with level of gene expression, strong individual secondary structural elements may be selected for to retard mRNA translation and to decrease gene expression. PMID:11606539

Carlini, D B; Chen, Y; Stephan, W

2001-10-01

160

A Study of the purine\\/pyrimidine codon occurrence with a reduced centered variable and an evaluation compared to the frequency statistic  

Microsoft Academic Search

With the three-letter alphabet {R,Y,N} (R = purine, Y = pyrimidine, N= R or Y), there are 26 codons (NNN being excluded): RNN, . ,NNY (six codons at two unspecified bases N), RRN,. ,NYY (12 codons at one unspecified base N), RRR ,.._, YYY (eight specified codons). A statistical methodology that uses the codon frequency and a reduced centered variable

CHRISTIAN J. MICHEL

1989-01-01

161

Characterization and expression of codon optimized soybean phytase gene in E. coli.  

PubMed

Phytic acid, the major storage form of phosphorus in plant seeds is degraded by the phytases to yield inositol and free phosphate, contributing thereby to the improved bioavailability of phytate phosphorus and essential minerals in plant foods and simultaneous reduction in phosphorus pollution of the terrestrial and aquatic ecosystems. As a possible strategy for altering seed phytate levels, the approach involving reduction of phytate content by ectopically expressing endogenous phytase gene during seed development of soybean (Glycine max L. cv. Pusa-20) was attempted in the present study. Semi-quantitative RT-PCR revealed the maximum expression of phytase gene transcripts in germinating cotyledons (approximately 10 days after germinations), compared to other vegetative tissues. A full-length phytase cDNA was amplified from the germinating seedlings by splicing by overlap extension (SOE)-PCR and its sequence analysis revealed an open-reading-frame of 1644 bp, including an N terminal signal peptide of 28 amino acids. Predicted amino acid sequence (547-aa) of molecular mass 62 kDa on alignment with related purple acid phosphatases in other plants shared five conserved domains and seven invariant amino acids involved in coordination of the metals in the binuclear center of purple acid phosphatases. Owing to a large number of E. coli low-usage codons in soybean phytase gene, the modified gene was cloned into a prokaryotic expression vector pET-28a (+) and its expression in E. coli was confirmed by SDS-PAGE and Western blot analysis. Bioassay of the crude expression product in E. coli revealed a functional phytase gene, showing a great potential for developing low phytate transgenic soybean through its seed-specific overexpression in the early stages of seed development. PMID:24772979

Singh, Pritee; Punjabi, Mansi; Jolly, Monica; Rai, R D; Sachdev, Archana

2013-12-01

162

Codon Bias is a Major Factor Explaining Phage Evolution in Translationally Biased Hosts  

E-print Network

Codon Bias is a Major Factor Explaining Phage Evolution in Translationally Biased Hosts Alessandra Carbone Received: 27 July 2007 / Accepted: 7 December 2007 Ã? Springer Science+Business Media, LLC 2008 spectrum of related phage species. Based on a large-scale codon bias analysis of 116 DNA phages hosted

Carbone, Alessandra

163

Feasibility Study of a Rotorcraft Health and Usage Monitoring System ( HUMS): Usage and Structural Life Monitoring Evaluation  

NASA Technical Reports Server (NTRS)

The objective of this study was to evaluate two techniques, Flight Condition Recognition (FCR) and Flight Load Synthesis (FLS), for usage monitoring and assess the potential benefits of extending the retirement intervals of life-limited components, thus reducing the operator's maintenance and replacement costs. Both techniques involve indirect determination of loads using measured flight parameters and subsequent fatigue analysis to calculate the life expended on the life-limited components. To assess the potential benefit of usage monitoring, the two usage techniques were compared to current methods of component retirement. In addition, comparisons were made with direct load measurements to assess the accuracy of the two techniques. The data that was used for the evaluation of the usage monitoring techniques was collected under an independent HUMS Flight trial program, using a commercially available HUMS and data recording system. The usage data collect from the HUMS trial aircraft was analyzed off-line using PC-based software that included the FCR and FLS techniques. In the future, if the technique prove feasible, usage monitoring would be incorporated into the onboard HUMS.

Dickson, B.; Cronkhite, J.; Bielefeld, S.; Killian, L.; Hayden, R.

1996-01-01

164

Refining the Balance of Attenuation and Immunogenicity of Respiratory Syncytial Virus by Targeted Codon Deoptimization of Virulence Genes  

PubMed Central

ABSTRACT Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in children for which there is no licensed vaccine. Live-attenuated RSV vaccines are the most clinically advanced in children, but achieving an optimal balance of attenuation and immunogenicity is challenging. One way to potentially retain or enhance immunogenicity of attenuated virus is to mutate virulence genes that suppress host immune responses. The NS1 and NS2 virulence genes of the RSV A2 strain were codon deoptimized according to either human or virus codon usage bias, and the resulting recombinant viruses (dNSh and dNSv, respectively) were rescued by reverse genetics. RSV dNSh exhibited the desired phenotype of reduced NS1 and NS2 expression. RSV dNSh was attenuated in BEAS-2B and primary differentiated airway epithelial cells but not in HEp-2 or Vero cells. In BALB/c mice, RSV dNSh exhibited a lower viral load than did A2, and yet it induced slightly higher levels of RSV-neutralizing antibodies than did A2. RSV A2 and RSV dNSh induced equivalent protection against challenge strains A/1997/12-35 and A2-line19F. RSV dNSh caused less STAT2 degradation and less NF-?B activation than did A2 in vitro. Serial passage of RSV dNSh in BEAS-2B cells did not result in mutations in the deoptimized sequences. Taken together, RSV dNSh was moderately attenuated, more immunogenic, and equally protective compared to wild-type RSV and genetically stable. PMID:25249281

Meng, Jia; Lee, Sujin; Hotard, Anne L.

2014-01-01

165

Modeling educational usage of Facebook  

Microsoft Academic Search

The purpose of this study is to design a structural model explaining how users could utilize Facebook for educational purposes. In order to shed light on the educational usage of Facebook, in constructing the model, the relationship between users' Facebook adoption processes and their educational use of Facebook were included indirectly while the relationship between users' purposes in using Facebook

Sacide Güzin Mazman; Yasemin Koçak Usluel

2010-01-01

166

Modeling Educational Usage of Facebook  

ERIC Educational Resources Information Center

The purpose of this study is to design a structural model explaining how users could utilize Facebook for educational purposes. In order to shed light on the educational usage of Facebook, in constructing the model, the relationship between users' Facebook adoption processes and their educational use of Facebook were included indirectly while the…

Mazman, Sacide Guzin; Usluel, Yasemin Kocak

2010-01-01

167

Code Usage Analysis System (CUAS)  

NASA Technical Reports Server (NTRS)

A set of computer programs is offered to aid a user in evaluating performance of an application program. The system provides reports of subroutine usage, program errors, and segment loading which occurred during the execution of an application program. It is presented in support of the development and validation of the space vehicle dynamics project.

Horsley, P. H.; Oliver, J. D.

1976-01-01

168

Marijuana usage and hypnotic susceptibility  

Microsoft Academic Search

Obtained anonymous self-reported drug usage data and Harvard Group Scale of Hypnotic Susceptibility scores from 282 college students. Frequent marihuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. There were no differences in primary suggestibility between principled nonusers and nonusers or between single-time, occasional, and frequent users. Frequent smoking of marihuana was significantly associated with S's

Louis R. Franzini; Roy D. McDonald

1973-01-01

169

Detecting differential usage of exons from RNA-seq data  

PubMed Central

RNA-seq is a powerful tool for the study of alternative splicing and other forms of alternative isoform expression. Understanding the regulation of these processes requires sensitive and specific detection of differential isoform abundance in comparisons between conditions, cell types, or tissues. We present DEXSeq, a statistical method to test for differential exon usage in RNA-seq data. DEXSeq uses generalized linear models and offers reliable control of false discoveries by taking biological variation into account. DEXSeq detects with high sensitivity genes, and in many cases exons, that are subject to differential exon usage. We demonstrate the versatility of DEXSeq by applying it to several data sets. The method facilitates the study of regulation and function of alternative exon usage on a genome-wide scale. An implementation of DEXSeq is available as an R/Bioconductor package. PMID:22722343

Anders, Simon; Reyes, Alejandro; Huber, Wolfgang

2012-01-01

170

Polymorphism distribution of prion protein codon 117, 129 and 171 in Taiwan.  

PubMed

Prion diseases compass transmissible spongiform neurodegenerative diseases from various causes, including the genetic and infectious ones. We investigated the prevalence of codon 117, 129 and 171 polymorphism in prion protein (PrP) in Taiwanese, mainly for the sake of the informative absence of this genetic distribution. Our subjects were 419 aged ones of Han ethic origin. We evaluated the PrP gene (PRNP) polymorphism by restriction fragment length polymorphism, after amplification of their genomic DNAs by polymerase chain reactions with specific primers, digested by restriction enzyme PvuII (for codon 117), NspI (for codon 129), and BbvI (for codon 171), respectively, and confirmed by nucleotide sequencing. All of the subjects were homozygotes at codon 117 (Ala/Ala, gca/gca) and 171 (Asn/Asn, aac/aac). There were no valine homozygotes (Val/Val) in our 419 subjects, and nine subjects (2.1%) showed methionine-valine heterozygosity (Mal/Val, atg/gtg). The methionine homozygotes (Met/Met) comprised the major population (97.9%), and the prevalence of distribution is different to that seen in Caucasians. The almost 100% conservation of the domain from codon 117 to 171 implies the warranty of PrP in cellular functions. The high prevalence of Met/Met alleles in Taiwan did not imply an increased risk of CJD, and the genetic susceptibility of CJD by codon 129 of PrP may be still elusive for the infectivity. PMID:17410475

Wang, Kaw-Chen; Wang, Vinchi; Sun, Ming-Chieh; Chiueh, Ti-I; Soong, Bing-Wen; Shan, Din-E

2007-01-01

171

GNAS codon 201 mutations are uncommon in intraductal papillary neoplasms of the bile duct  

PubMed Central

Background Activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Intraductal papillary neoplasms of the bile ducts (IPNBs) morphologically resemble pancreatic IPMNs. This study sought to assess the mutational status of GNAS at codon 201 in IPNBs. Methods Thirty-four patients were included. DNA from microdissected IPNBs was subjected to a polymerase chain reaction and ligation method for the detection of GNAS mutations at codon 201 and of KRAS mutations at codon 12. Mutational status was compared with clinical and pathologic data. Results The IPNBs had a median diameter of 3.5 cm and were located intrahepatically (n= 6), extrahepatically (n= 13), both intra- and extrahepatically (n= 4) or in the gallbladder (intracystic papillary neoplasms, n= 11). Most exhibited pancreatobiliary differentiation (n= 20), high-grade dysplasia (n= 26) and an associated adenocarcinoma (n= 20). Analysis of GNAS codon 201 identified only one mutant sample in a multifocal intestinal subtype intrahepatic IPNB with high-grade dysplasia. Six lesions harboured a KRAS codon 12 mutation. Conclusions GNAS codon 201 mutations are uncommon in IPNBs, by contrast with pancreatic IPMNs. More comprehensive molecular profiling is needed to uncover the pathways involved in IPNB development. PMID:22954004

Matthaei, Hanno; Wu, Jian; Dal Molin, Marco; Debeljak, Marija; Lingohr, Philipp; Katabi, Nora; Klimstra, David S; Adsay, N Volkan; Eshleman, James R; Schulick, Richard D; Kinzler, Kenneth W; Vogelstein, Bert; Hruban, Ralph H; Maitra, Anirban

2012-01-01

172

Allosteric mechanism for codon-dependent tRNA selection on ribosomes.  

PubMed Central

We suggest that the interaction between a codon and its cognate tRNA induces conformational changes in the tRNA. We further suggest that sites on the ribosome preferentially bind tRNA in those conformations which require proper matching of codon and anticodon. According to this model, the codon functions as an allosteric effector which influences the conformation at various sites in the tRNA. This is made possible by the ribosome, which we suggest traps tRNA molecules in those conformation states that maximize the energy difference between cognate and noncognate codon-anticodon interactions. Studies of the interactions between tRNA molecules and their cognate codons in the absence of the ribosome have suggested that triplet-triplet interaction between codon and anticodon is far too weak to account for the specificity of the tRNA selection mechanism during protein synthesis. In contrast, we suggest that such affinity measurements do not adequately describe the interaction between a codon and its cognate tRNA. Thus, such experiments can not detect conformational changes in the tRNA, and, in particular, those stabilized by the ribosome. PMID:1060103

Kurland, C G; Rigler, R; Ehrenberg, M; Blomberg, C

1975-01-01

173

Suppression of Premature Termination Codons as a Therapeutic Approach  

PubMed Central

In this review, we describe our current understanding of translation termination and pharmacological agents that influence the accuracy of this process. A number of drugs have been identified that induce suppression of translation termination at in-frame premature termination codons (PTCs; also known as nonsense mutations) in mammalian cells. We discuss efforts to utilize these drugs to suppress disease-causing PTCs that result in the loss of protein expression and function. In-frame PTCs represent a genotypic subset of mutations that make up ~11% of all known mutations that cause genetic diseases, and millions of patients have diseases attributable to PTCs. Current approaches aimed at reducing the efficiency of translation termination at PTCs (referred to as PTC suppression therapy) have the goal of alleviating the phenotypic consequences of a wide range of genetic diseases. Suppression therapy is currently in clinical trials for treatment of several genetic diseases caused by PTCs, and preliminary results suggest that some patients have shown clinical improvements. While current progress is promising, we discuss various approaches that may further enhance the efficiency of this novel therapeutic approach. PMID:22672057

Keeling, Kim M.; Wang, Dan; Conard, Sara E.; Bedwell, David M.

2012-01-01

174

NECTAR: a database of codon-centric missense variant annotations  

PubMed Central

NECTAR (Non-synonymous Enriched Coding muTation ARchive; http://nectarmutation.org) is a database and web application to annotate disease-related and functionally important amino acids in human proteins. A number of tools are available to facilitate the interpretation of DNA variants identified in diagnostic or research sequencing. These typically identify previous reports of DNA variation at a given genomic location, predict its effects on transcript and protein sequence and may predict downstream functional consequences. Previous reports and functional annotations are typically linked by the genomic location of the variant observed. NECTAR collates disease-causing variants and functionally important amino acid residues from a number of sources. Importantly, rather than simply linking annotations by a shared genomic location, NECTAR annotates variants of interest with details of previously reported variation affecting the same codon. This provides a much richer data set for the interpretation of a novel DNA variant. NECTAR also identifies functionally equivalent amino acid residues in evolutionarily related proteins (paralogues) and, where appropriate, transfers annotations between them. As well as accessing these data through a web interface, users can upload batches of variants in variant call format (VCF) for annotation on-the-fly. The database is freely available to download from the ftp site: ftp://ftp.nectarmutation.org. PMID:24297257

Gong, Sungsam; Ware, James S.; Walsh, Roddy; Cook, Stuart A.

2014-01-01

175

Virus-Host Coevolution: Common Patterns of Nucleotide Motif Usage in Flaviviridae and Their Hosts  

PubMed Central

Virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. Flaviviridae family is composed of fast evolving RNA viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. These host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. Flaviviridae viruses which infect a single host lineage would be subjected to specific host-induced pressures and, therefore, selected by them. In this work we compare the genomic evolutionary patterns of Flaviviridae viruses and their hosts in an attempt to uncover coevolutionary processes inducing common features in such disparate groups. Especially, we have analyzed dinucleotide and codon usage patterns in the coding regions of vertebrate and invertebrate organisms as well as in Flaviviridae viruses which specifically infect one or both host types. The two host groups possess very distinctive dinucleotide and codon usage patterns. A pronounced CpG under-representation was found in the vertebrate group, possibly induced by the methylation-deamination process, as well as a prominent TpA decrease. The invertebrate group displayed only a TpA frequency reduction bias. Flaviviridae viruses mimicked host nucleotide motif usage in a host-specific manner. Vertebrate-infecting viruses possessed under-representation of CpG and TpA, and insect-only viruses displayed only a TpA under-representation bias. Single-host Flaviviridae members which persistently infect mammals or insect hosts (Hepacivirus and insect-only Flavivirus, respectively) were found to posses a codon usage profile more similar to that of their hosts than to related Flaviviridae. We demonstrated that vertebrates and mosquitoes genomes are under very distinct lineage-specific constraints, and Flaviviridae viruses which specifically infect these lineages appear to be subject to the same evolutionary pressures that shaped their host coding regions, evidencing the lineage-specific coevolutionary processes between the viral and host groups. PMID:19617912

Lobo, Francisco P.; Mota, Bruno E. F.; Pena, Sérgio D. J.; Azevedo, Vasco; Macedo, Andréa M.; Tauch, Andreas; Machado, Carlos R.; Franco, Glória R.

2009-01-01

176

40 CFR 35.6320 - Usage rate.  

Code of Federal Regulations, 2013 CFR

...activity, and operable unit, as applicable, the recipient must apply a usage rate. The recipient must submit...activity, and operable unit, as applicable, and must apply the usage rate to calculate equipment...activity, and operable unit, as applicable....

2013-07-01

177

40 CFR 35.6320 - Usage rate.  

Code of Federal Regulations, 2011 CFR

...activity, and operable unit, as applicable, the recipient must apply a usage rate. The recipient must submit...activity, and operable unit, as applicable, and must apply the usage rate to calculate equipment...activity, and operable unit, as applicable....

2011-07-01

178

40 CFR 35.6320 - Usage rate.  

Code of Federal Regulations, 2012 CFR

...activity, and operable unit, as applicable, the recipient must apply a usage rate. The recipient must submit...activity, and operable unit, as applicable, and must apply the usage rate to calculate equipment...activity, and operable unit, as applicable....

2012-07-01

179

40 CFR 35.6320 - Usage rate.  

Code of Federal Regulations, 2010 CFR

...activity, and operable unit, as applicable, the recipient must apply a usage rate. The recipient must submit...activity, and operable unit, as applicable, and must apply the usage rate to calculate equipment...activity, and operable unit, as applicable....

2010-07-01

180

Identifying protein-coding genes and synonymous constraint elements using phylogenetic codon models  

E-print Network

We develop novel methods for comparative genomics analysis of protein-coding genes using phylogenetic codon models, in pursuit of two main lines of biological investigation: First, we develop PhyloCSF, an algorithm based ...

Lin, Michael F. (Michael Fong-Jay)

2012-01-01

181

Genetic association between p53 codon 72 polymorphism and risk of cutaneous squamous cell carcinoma.  

PubMed

This study was designed to obtain a conclusive result about the relevance of p53 codon 72 polymorphism to the risk of cutaneous squamous cell carcinoma (SCC). We performed an updated meta-analysis of 3,792 subjects (1,349 cancer cases and 2,443 controls) to summarize the data available for p53 codon 72 polymorphism and SCC risk. The association was estimated by odds ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis showed no statistical significance for SCC risk associated with any of the genetic models of p53 codon 72 polymorphism. The analyses by ethnic subgroup also failed to produce significant associations. This study suggests that p53 codon 72 polymorphism does not appear to represent a significant susceptibility factor for SCC in Caucasians. PMID:24353089

Liu, Ting; Lei, Zeyuan; Pan, ZhengYing; Chen, Yu; Li, Xiang; Mao, TongChun; He, Qian; Fan, Dongli

2014-04-01

182

Evidence of abundant stop codon readthrough in Drosophila and other Metazoa  

E-print Network

While translational stop codon readthrough is often used by viral genomes, it has been observed for only a handful of eukaryotic genes. We previously used comparative genomics evidence to recognize protein-coding regions ...

Jungreis, Irwin

183

Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes  

PubMed Central

Summary: The correct translation of mRNA depends critically on the ability to initiate at the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the 5? end of the mRNA and then inspects the leader base by base for an AUG in a suitable context, using complementarity with the anticodon of methionyl initiator tRNA (Met-tRNAiMet) as the key means of identifying AUG. Over the past decade, a combination of yeast genetics, biochemical analysis in reconstituted systems, and structural biology has enabled great progress in deciphering the mechanism of ribosomal scanning. A robust molecular model now exists, describing the roles of initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in stabilizing an “open” conformation of the 40S subunit with Met-tRNAiMet bound in a low-affinity state conducive to scanning and in triggering rearrangement into a “closed” conformation incompatible with scanning, which features Met-tRNAiMet more tightly bound to the “P” site and base paired with AUG. It has also emerged that multiple DEAD-box RNA helicases participate in producing a single-stranded “landing pad” for the 40S subunit and in removing the secondary structure to enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded form for base-by-base inspection in the P site. PMID:21885680

Hinnebusch, Alan G.

2011-01-01

184

Relationship Between p53 Codon 72 Polymorphism and Susceptibility to Sunburn and Skin Cancer  

Microsoft Academic Search

Upregulation of p53 protein induces either growth arrest or apoptosis in response to cellular injury This is signaled from a highly conserved p53 domain between codons 64 and 92, where a functional polymorphism results in either a proline (p53-72P) or an arginine (p53-72R) at codon 72. Preliminary studies suggest that p53-72R may be a risk factor for cervical cancer and,

Jane M. McGregor; Catherine A. Harwood; Louise Brooks; Sheila A. Fisher; Deirdre A. Kelly; Jenny O'nions; Antony R. Young; Thiru Surentheran; Judith Breuer; Thomas P. Millard; Cathryn M. Lewis; Irene M. Leigh; Alan Storey; Timothy Crook

2002-01-01

185

Leakiness of termination codons in mitochondrial mutants of the yeast Saccharomyces cerevisiae  

Microsoft Academic Search

Seven mutants in exon 1 of the mitochondrial cob gene in yeast are described with respect to their translation products, RNA pattern, and deoxyribonucleotide sequence alteration(s). Sequence analysis of the mutations, which previously were shown to cause premature termination of apocytochrome b, revealed that two of them directly transform sense codons to chain-termination codons, whereas the other four are frame-shift

Brigitte Weiss-Brummer; Alexander Hiittenhofer; Fritz Kaudewitz

1984-01-01

186

Analysis of PRNP Gene Codon 129 Polymorphism in the Greek Population  

Microsoft Academic Search

Creutzfeldt–Jakob disease (CJD) is a fatal transmissible neurodegenerative prion disease with a rapid progression comprising\\u000a familial, sporadic, iatrogenic and variant forms. A polymorphism at codon 129 of PRNP gene has been implicated in the development\\u000a of variant CJD. We examined Met\\/Val allele frequencies and the genotype distribution, with respect to the polymorphic codon\\u000a 129 of PRNP gene in 348 healthy

Angelica A. Saetta; Nikolaos V. Michalopoulos; George Malamis; Polyanthi I. Papanastasiou; Niki Mazmanian; Maria Karlou; Anastasios Kouzoupis; Penelope Korkolopoulou; Efstratios Patsouris

2006-01-01

187

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.  

PubMed

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. PMID:22041054

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

2012-01-15

188

High level production of ?-galactosidase exhibiting excellent milk-lactose degradation ability from Aspergillus oryzae by codon and fermentation optimization.  

PubMed

A ?-galactosidase gene from Aspergillus oryzae was engineered utilizing codon usage optimization to be constitutively and highly expressed in the Pichia pastoris SMD1168H strain in a high-cell-density fermentation. After fermentation for 96 h in a 50-L fermentor using glucose and glycerol as combined carbon sources, the recombinant enzyme in the culture supernatant had an activity of 4,239.07 U mL(-1) with o-nitrophenyl-?-D-galactopyranoside as the substrate, and produced a total of extracellular protein content of 7.267 g L(-1) in which the target protein (6.24 g L(-1)) occupied approximately 86 %. The recombinant ?-galactosidase exhibited an excellent lactose hydrolysis ability. With 1,000 U of the enzyme in 100 mL milk, 92.44 % lactose was degraded within 24 h at 60 °C, and the enzyme could also accomplish the hydrolysis at low temperatures of 37, 25, and 10 °C. Thus, this engineered strain had significantly higher fermentation level of A. oryzae lactase than that before optimization and the ?-galactosidase may have a good application potential in whey and milk industries. PMID:24435763

Zhao, Qianqian; Liu, Fei; Hou, Zhongwen; Yuan, Chao; Zhu, Xiqiang

2014-03-01

189

Clinical relevance of KRAS mutations in codon 13: Where are we?  

PubMed

Recent advances in molecular diagnosis and the trend towards personalized medicine have made colorectal cancer one of the tumors where therapies have significantly improved patient survival after metastasis development. KRAS mutations in codon 12 and 13 are recognized biomarkers that are analyzed in clinic previously for anti-EGFR therapies administration. Since originally mutations in both codons were considered as a predictor of lack of response to cetuximab or panitumumab, the European Medicines Agency and the US Food and Drug Administration suggested that patients harboring any of those mutations should be excluded from the treatment. However, subsequent retrospective analysis has shown that mutations in codon 12 and codon 13 of KRAS gene could be different in their biological characteristics and as a result could confer variable effects in patients. In addition and increasing and sometimes contradictory number of solutions have been published demonstrating that patients with mutations in codon 13 could have worse outcome but could obtain a significant clinical benefit from anti-EGFR therapies. Here, we review and update the latest data on the biological role leading to a predictive outcome and benefit from anti-EGFR antibodies in patients with specific KRAS mutations in codon 13. PMID:24051306

Er, Tze-Kiong; Chen, Chih-Chieh; Bujanda, Luis; Herreros-Villanueva, Marta

2014-02-01

190

New insights into the incorporation of natural suppressor tRNAs at stop codons in Saccharomyces cerevisiae  

PubMed Central

Stop codon readthrough may be promoted by the nucleotide environment or drugs. In such cases, ribosomes incorporate a natural suppressor tRNA at the stop codon, leading to the continuation of translation in the same reading frame until the next stop codon and resulting in the expression of a protein with a new potential function. However, the identity of the natural suppressor tRNAs involved in stop codon readthrough remains unclear, precluding identification of the amino acids incorporated at the stop position. We established an in vivo reporter system for identifying the amino acids incorporated at the stop codon, by mass spectrometry in the yeast Saccharomyces cerevisiae. We found that glutamine, tyrosine and lysine were inserted at UAA and UAG codons, whereas tryptophan, cysteine and arginine were inserted at UGA codon. The 5? nucleotide context of the stop codon had no impact on the identity or proportion of amino acids incorporated by readthrough. We also found that two different glutamine tRNAGln were used to insert glutamine at UAA and UAG codons. This work constitutes the first systematic analysis of the amino acids incorporated at stop codons, providing important new insights into the decoding rules used by the ribosome to read the genetic code. PMID:25056309

Blanchet, Sandra; Cornu, David; Argentini, Manuela; Namy, Olivier

2014-01-01

191

New insights into the incorporation of natural suppressor tRNAs at stop codons in Saccharomyces cerevisiae.  

PubMed

Stop codon readthrough may be promoted by the nucleotide environment or drugs. In such cases, ribosomes incorporate a natural suppressor tRNA at the stop codon, leading to the continuation of translation in the same reading frame until the next stop codon and resulting in the expression of a protein with a new potential function. However, the identity of the natural suppressor tRNAs involved in stop codon readthrough remains unclear, precluding identification of the amino acids incorporated at the stop position. We established an in vivo reporter system for identifying the amino acids incorporated at the stop codon, by mass spectrometry in the yeast Saccharomyces cerevisiae. We found that glutamine, tyrosine and lysine were inserted at UAA and UAG codons, whereas tryptophan, cysteine and arginine were inserted at UGA codon. The 5' nucleotide context of the stop codon had no impact on the identity or proportion of amino acids incorporated by readthrough. We also found that two different glutamine tRNA(Gln) were used to insert glutamine at UAA and UAG codons. This work constitutes the first systematic analysis of the amino acids incorporated at stop codons, providing important new insights into the decoding rules used by the ribosome to read the genetic code. PMID:25056309

Blanchet, Sandra; Cornu, David; Argentini, Manuela; Namy, Olivier

2014-11-01

192

The Characteristics of Rare Codon Clusters in the Genome and Proteins of Hepatitis C Virus; a Bioinformatics Look  

PubMed Central

BACKGROUND Recent studies suggest that rare codon clusters are functionally important for protein activity. METHODS Here, for the first time we analyzed and reported rare codon clusters in Hepatitis C Virus (HCV) genome and then identified the location of these rare codon clusters in the structure of HCV protein. This analysis was performed using the Sherlocc program that detects statistically relevant conserved rare codon clusters. RESULTS By this program, we identified the rare codon cluster in three regions of HCV genome; NS2, NS3, and NS5A coding sequence of HCV genome. For further understanding of the role of these rare codon clusters, we studied the location of these rare codon clusters and critical residues in the structure of NS2, NS3 and NS5A proteins. We identified some critical residues near or within rare codon clusters. It should be mentioned that characteristics of these critical residues such as location and situation of side chains are important in assurance of the HCV life cycle. CONCLUSION The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins. Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins. This information is helpful in development of new avenues for vaccine and treatment protocols. PMID:25349685

Fattahi, Mohammadreza; Malekpour, Abdorrasoul; Mortazavi, Mojtaba; Safarpour, Alireza; Naseri, Nasrin

2014-01-01

193

Kinetic modelling indicates that fast-translating codons can coordinate cotranslational protein folding by avoiding misfolded intermediates  

NASA Astrophysics Data System (ADS)

It has been observed for several proteins that slowing down the rate at which individual codons are translated can increase their probability of cotranslational protein folding, while speeding up codon translation can decrease it. Here we investigate whether or not this inverse relationship between translation speed and the cotranslational folding probability is a general phenomenon or if other scenarios are possible. We first derive chemical kinetic equations that relate individual codon translation rates to the probability that a domain will fold, populate an intermediate or misfold, and examine the cotranslational folding scenarios that are possible within these models. We find that speeding up codon translation through misfolding-prone segments can, in some cases, increase the folding probability of a domain immediately before the nascent protein is released from the ribosome and decrease its chances of misfolding. Thus, for some proteins fast-translating codons could be as important as slow-translating codons in coordinating cotranslational protein folding.

O'Brien, Edward P.; Vendruscolo, Michele; Dobson, Christopher M.

2014-01-01

194

Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy  

PubMed Central

To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm3 (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy. PMID:19440454

Tossonian, Harout K; Raffa, Jesse D; Grebely, Jason; Viljoen, Mark; Mead, Annabel; Khara, Milan; McLean, Mark; Krishnamurthy, Ashok; DeVlaming, Stanley; Conway, Brian

2007-01-01

195

The effect of tRNA levels on decoding times of mRNA codons  

PubMed Central

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 <0.006); in addition, we show that when considering tRNA concentrations, codons 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. PMID:25056313

Dana, Alexandra; Tuller, Tamir

2014-01-01

196

Two-step model of stop codon recognition by eukaryotic release factor eRF1  

PubMed Central

Release factor eRF1 plays a key role in the termination of protein synthesis in eukaryotes. The eRF1 consists of three domains (N, M and C) that perform unique roles in termination. Previous studies of eRF1 point mutants and standard/variant code eRF1 chimeras unequivocally demonstrated a direct involvement of the highly conserved N-domain motifs (NIKS, YxCxxxF and GTx) in stop codon recognition. In the current study, we extend this work by investigating the role of the 41 invariant and conserved N-domain residues in stop codon decoding by human eRF1. Using a combination of the conservative and non-conservative amino acid substitutions, we measured the functional activity of >80 mutant eRF1s in an in vitro reconstituted eukaryotic translation system and selected 15 amino acid residues essential for recognition of different stop codon nucleotides. Furthermore, toe-print analyses provide evidence of a conformational rearrangement of ribosomal complexes that occurs during binding of eRF1 to messenger RNA and reflects stop codon decoding activity of eRF1. Based on our experimental data and molecular modelling of the N-domain at the ribosomal A site, we propose a two-step model of stop codon decoding in the eukaryotic ribosome. PMID:23435318

Kryuchkova, Polina; Grishin, Alexander; Eliseev, Boris; Karyagina, Anna; Frolova, Ludmila; Alkalaeva, Elena

2013-01-01

197

Evidence of abundant stop codon readthrough in Drosophila and other metazoa.  

PubMed

While translational stop codon readthrough is often used by viral genomes, it has been observed for only a handful of eukaryotic genes. We previously used comparative genomics evidence to recognize protein-coding regions in 12 species of Drosophila and showed that for 149 genes, the open reading frame following the stop codon has a protein-coding conservation signature, hinting that stop codon readthrough might be common in Drosophila. We return to this observation armed with deep RNA sequence data from the modENCODE project, an improved higher-resolution comparative genomics metric for detecting protein-coding regions, comparative sequence information from additional species, and directed experimental evidence. We report an expanded set of 283 readthrough candidates, including 16 double-readthrough candidates; these were manually curated to rule out alternatives such as A-to-I editing, alternative splicing, dicistronic translation, and selenocysteine incorporation. We report experimental evidence of translation using GFP tagging and mass spectrometry for several readthrough regions. We find that the set of readthrough candidates differs from other genes in length, composition, conservation, stop codon context, and in some cases, conserved stem-loops, providing clues about readthrough regulation and potential mechanisms. Lastly, we expand our studies beyond Drosophila and find evidence of abundant readthrough in several other insect species and one crustacean, and several readthrough candidates in nematode and human, suggesting that functionally important translational stop codon readthrough is significantly more prevalent in Metazoa than previously recognized. PMID:21994247

Jungreis, Irwin; Lin, Michael F; Spokony, Rebecca; Chan, Clara S; Negre, Nicolas; Victorsen, Alec; White, Kevin P; Kellis, Manolis

2011-12-01

198

Hemoglobin E and codon 17 nonsense: Two ?-globin gene mutations common in Southeast Asia detected by the use of ARMS  

Microsoft Academic Search

Summary Hemoglobin E (codon 26 GAG?AAG) and codon 17 nonsense (AAG?TAG), two clinically important mutations of the ß-globin gene, are common in Southeast Asia. The detection of these mutations using allele-specific PCR is described. Together with the previously reported method for the detection of the common Southeast asian codon 41–42 frameshift mutation (del CTTT), it is possible to identify the

H. Steger; A. Eigel; G. Flatz; J. Horst

1993-01-01

199

Association of Vancomycin-Resistant Enterococcus Bacteremia and Ceftriaxone Usage  

PubMed Central

Objective Vancomycin-resistant Enterococci (VRE) have become a public health concern with implications for patient mortality and costs. Hospital antibiotic usage may impact VRE incidence, but the relationship is poorly understood. Animal investigations suggest ceftriaxone may be associated with VRE proliferation. We measured antimicrobial usage and VRE bloodstream infection (BSI) incidence to test our hypothesis that increased ceftriaxone use would be associated with a higher incidence of VRE-BSI. Setting The University of Alabama at Birmingham Medical Center is a 900-bed urban tertiary-care hospital Methods Retrospective analysis of antimicrobial usage and VRE-BSI from 2005 to 2008 (43 months). Antimicrobial usage quantified as days of therapy/1,000 patient-days (DOT). VRE-BSI incidence calculated as cases/1,000 patient-days. Negative binomial regression with adjustment for correlation between consecutive observations measured the association between antimicrobial usage and VRE-BSI incidence at the hospital- and care-unit levels. Results VRE-BSI incidence increased from 0.06 to 0.17 infections/1,000 patient-days. Hospital VRE-BSI incidence was associated with prior-month ceftriaxone DOT (Incidence Rate Ratio 1.38 per 10 DOT; p=0.005). After controlling for ceftriaxone, prior-month cephalosporin use (class) was not predictive of VRE-BSI (p=0.70). Similarly, prior-month use of piperacillin-tazobactam, ceftazidime, cefepime, cefazolin, or vancomycin was not predictive of VRE-BSI when considered individually (p?0.4 for all comparisons). The final model suggests that type of intensive care unit was related to VRE-BSI incidence. Conclusions Ceftriaxone use in the prior month, but not cephalosporin (class) or vancomycin use, was related to VRE-BSI incidence. These findings suggest that an antimicrobial stewardship program that limits ceftriaxone may reduce nosocomial VRE-BSI incidence. PMID:22669234

McKinnell, James A.; Kunz, Danielle F.; Chamot, Eric; Patel, Mukesh; Shirley, Rhett M.; Moser, Stephen A.; Baddley, John W.; Pappas, Peter G.; Miller, Loren G.

2013-01-01

200

UGA suppression by normal tRNA Trp in Escherichia coli: codon context effects.  

PubMed Central

The nucleotide sequences at the 3' side of in-phase UGA termination codons in mRNAs of various prokaryotic genes were re-examined. An adenine (A) residue is found to be adjacent to the 3' side of UGA in mRNAs which code for readthrough proteins by the suppression of UGA by normal Escherichia coli tRNA Trp. It is suggested that the nature of the nucleotide following a UGA codon determines whether the UGA signals inefficiently or efficiently the termination of polypeptide chain synthesis: an A residue at this position permits the UGA readthrough process. PMID:7015288

Engelberg-Kulka, H

1981-01-01

201

Effect of sequence context at stop codons on efficiency of reinitiation in GCN4 translational control.  

PubMed Central

Translational control of the GCN4 gene involves two short open reading frames in the mRNA leader (uORF1 and uORF4) that differ greatly in the ability to allow reinitiation at GCN4 following their own translation. The low efficiency of reinitiation characteristic of uORF4 can be reconstituted in a hybrid element in which the last codon of uORF1 and 10 nucleotides 3' to its stop codon (the termination region) are substituted with the corresponding nucleotides from uORF4. To define the features of these 13 nucleotides that determine their effects on reinitiation, we separately randomized the sequence of the third codon and termination region of the uORF1-uORF4 hybrid and selected mutant alleles with the high-level reinitiation that is characteristic of uORF1. The results indicate that many different A+U-rich triplets present at the third codon of uORF1 can overcome the inhibitory effect of the termination region derived from uORF4 on the efficiency of reinitiation at GCN4. Efficient reinitiation is not associated with codons specifying a particular amino acid or isoacceptor tRNA. Similarly, we found that a diverse collection of A+U-rich sequences present in the termination region of uORF1 could restore efficient reinitiation at GCN4 in the presence of the third codon derived from uORF4. To explain these results, we propose that reinitiation can be impaired by stable base pairing between nucleotides flanking the uORF1 stop codon and either the tRNA which pairs with the third codon, the rRNA, or sequences located elsewhere in GCN4 mRNA. We suggest that these interactions delay the resumption of scanning following peptide chain termination at the uORF and thereby lead to ribosome dissociation from the mRNA. Images PMID:8264629

Grant, C M; Hinnebusch, A G

1994-01-01

202

Computer Science MAPO: Mining API Usages from  

E-print Network

Computer Science MAPO: Mining API Usages from Open Source Repositories Tao Xie Department of Computer Science North Carolina State University, USA Jian Pei Department of Computer Science Simon Fraser University, Canada ·http://ase.csc.ncsu.edu/ #12;Computer Science Learning API Usages is Challenging ·org

Xie, Tao

203

Media Usage as Health Segmentation Variables  

Microsoft Academic Search

The purpose of this research is to contrast a traditional audience segmentation model that uses demographics and health evaluations against a model that uses these same variables plus media usage variables. The goal was to determine whether media usage variables—typically not used in health segmentation studies—add predictive power in determining health behaviors and attitudes. The results of the analysis showed

Shelly Rodgers; Qimei Chen; Margaret Duffy; Kenneth Fleming

2007-01-01

204

Physical Educators' Technology Competencies and Usage  

ERIC Educational Resources Information Center

The purpose of this study was to examine K-12 physical education teachers' perceptions of ability and usage of technology. Physical educators (n = 114) completed the Physical Education Technology Usage Survey assessing their perceived technology competency, how and why they utilize technology, challenges they face in implementing technology, and…

Woods, Marianne L.; Goc Karp, Grace; Miao, Hui; Perlman, Dana

2008-01-01

205

Style and Usage Guidelines for Written Communications  

E-print Network

Style and Usage Guidelines for Written Communications Administrative and Business Services #12;Table of Contents Introduction Common Grammar and Usage Problems Frequently Misused Words Parallel of Words An Economy of Words Unclear Antecedents Sentences that Begin with "There" and "It" Clarity

Rose, Michael R.

206

Patterns of Drug Usage Among Vietnam Veterans.  

ERIC Educational Resources Information Center

A factor analysis was performed on an intercorrelation matrix of reported drug usage frequencies for seven drug categories at two consecutive periods of time. Subjects were 1,010 Army Vietnam veterans in pay grade E6 or below, aged 26 years or less. Retrospective reporting identified drug usage prior to a tour of Vietnam and during the tour. Four…

Fisher, Allan H., Jr.; And Others

207

[Healthcare usage by elderly people].  

PubMed

The newest demographic changes in the world and in our country show slow population increase and accelerated growth of elderly population. Apart from this growth of elderly population today we are experiencing increase in life expectancy. Our goal is to present socioeconomic status, usage of health services and patients satisfaction with those services. Our research includes 120 persons older than 65 years living in rural areas of Vares municipality. The data was collected in the period of 01/04/2007 to 01/05/2007. Municipality register provided us with data for elderly population using random sampling method. Examination was carried out using questionnaire papers especially formulated for our research. Statistical analysis includes elements of descriptive statistics X2 and the test of correlation; results with p<05 will be used in our research. Research variables are: sex, age, education level, salary, profession before retirement, number of visits to MD as well to a specialist, days spent in hospital and overall satisfaction with health care services. PMID:18232283

Dzubur, Amela; Brkljaci?, Morana; Kevri?, E

2007-01-01

208

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

209

TTG serves as an initiation codon for the ribosomal protein MvaS7 from the archaeon Methanococcus vannielii.  

PubMed

The ribosomal protein MvaS7 from the methanogenic archaeon Methanococcus vannielii is a protein of 188 amino acids, i.e., it is 42 amino acids longer than previously suggested. The triplet TTG serves as a start codon. The methanogenic translation initiation region that includes the rare TTG start codon is recognized in Escherichia coli. PMID:7592355

Golderer, G; Dlaska, M; Gröbner, P; Piendl, W

1995-10-01

210

Association of TP53 gene codon 72 polymorphism with endometriosis risk in Isfahan  

PubMed Central

Background: Endometriosis is a female health disorder that occurs when cells from the lining of the uterus grow in other areas of the body. The cause of endometriosis is unknown. Objective: The purpose of this study was to investigate TP53 gene codon 72 polymorphism in women with endometriosis and compared it with healthy samples in Isfahan. Materials and Methods: We undertook a case-control study to examine the possible association of the TP53 gene codon 72 polymorphism with the risk of endometriosis in Isfahan. Ninety whole blood specimens from normal people as controls and ninety endometriosis specimens were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction. Results: Frequency of genotype Arg/Arg (Arginine/Arginine) in the samples of endometriosis was 28.9% and in healthy samples 42.2%. Frequency of genotype Pro/Pro (Proline/Proline) in the samples of endometriosis was 15.6% and in healthy ones. Frequency of heterozygote's Arg/Pro was 55.6% in endometriosis samples and 54.45% in healthy ones 3.3%. By comparing statistical genotype Pro/Pro with two other genotypes in both groups there was a statistical meaningful difference between control group and endometriosis group. [p=0.009, CI=95%, OR=5.34 (1047-19.29)]. Conclusion: Recent research shows that genotype Pro/Pro codon72 exon4 TP53 gene may be one predisposing genetic factor for endometriosis in Isfahan. PMID:24639781

Nikbakht Dastjerdi, Mehdi; Aboutorabi, Roshanak; Eslami Farsani, Bahram

2013-01-01

211

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

Microsoft Academic Search

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

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

2009-01-01

212

Differences in codon bias cannot explain differences in translational power among microbes  

Microsoft Academic Search

BACKGROUND: Translational power is the cellular rate of protein synthesis normalized to the biomass invested in translational machinery. Published data suggest a previously unrecognized pattern: translational power is higher among rapidly growing microbes, and lower among slowly growing microbes. One factor known to affect translational power is biased use of synonymous codons. The correlation within an organism between expression level

Les Dethlefsen; Thomas M. Schmidt

2005-01-01

213

Strong short-range correlations and dichotomic codon classes in coding DNA sequences  

NASA Astrophysics Data System (ADS)

The study of correlation structures in DNA sequences is of great interest because it allows us to obtain structural and functional information about underlying genetic mechanisms. In this paper we present a study of the correlation structure of protein coding sequences of DNA based on a recently developed mathematical representation of the genetic code. A fundamental consequence of such representation is that codons can be assigned a parity class (odd-even). Such parity can be obtained by means of a nonlinear algorithm acting on the chemical character of the codon bases. In the same setting the Rumer’s class can be naturally described and a new dichotomic class, the hidden class, can be defined. Moreover, we show that the set of DNA’s base transformations associated to the three dichotomic classes can be put in a compact group-theoretic framework. We use the dichotomic classes as a coding scheme for DNA sequences and study the mutual dependence between such classes. The same analysis is carried out also on the chemical dichotomies of DNA bases. In both cases, the statistical analysis is performed by using an entropy-based dependence metric possessing many desirable properties. We obtain meaningful tests for mutual dependence by using suitable resampling techniques. We find strong short-range correlations between certain combinations of dichotomic codon classes. These results support our previous hypothesis that codon classes might play an active role in the organization of genetic information.

Gonzalez, Diego Luis; Giannerini, Simone; Rosa, Rodolfo

2008-11-01

214

MACSE: Multiple Alignment of Coding SEquences Accounting for Frameshifts and Stop Codons  

PubMed Central

Until now the most efficient solution to align nucleotide sequences containing open reading frames was to use indirect procedures that align amino acid translation before reporting the inferred gap positions at the codon level. There are two important pitfalls with this approach. Firstly, any premature stop codon impedes using such a strategy. Secondly, each sequence is translated with the same reading frame from beginning to end, so that the presence of a single additional nucleotide leads to both aberrant translation and alignment. We present an algorithm that has the same space and time complexity as the classical Needleman-Wunsch algorithm while accommodating sequencing errors and other biological deviations from the coding frame. The resulting pairwise coding sequence alignment method was extended to a multiple sequence alignment (MSA) algorithm implemented in a program called MACSE (Multiple Alignment of Coding SEquences accounting for frameshifts and stop codons). MACSE is the first automatic solution to align protein-coding gene datasets containing non-functional sequences (pseudogenes) without disrupting the underlying codon structure. It has also proved useful in detecting undocumented frameshifts in public database sequences and in aligning next-generation sequencing reads/contigs against a reference coding sequence. MACSE is distributed as an open-source java file executable with freely available source code and can be used via a web interface at: http://mbb.univ-montp2.fr/macse. PMID:21949676

Ranwez, Vincent; Harispe, Sébastien; Delsuc, Frédéric; Douzery, Emmanuel J. P.

2011-01-01

215

DNA Mismatch Repair and Synonymous Codon Evolution in Mammals Adam Eyre-Walker  

E-print Network

DNA Mismatch Repair and Synonymous Codon Evolution in Mammals Adam Eyre-Walker Institute of Cell to predict the expected relationship between the rate of substitution and G+C content at silent sites. It was found that the silent-substitution rate should decline with increasing G+C content over most of the G

Eyre-Walker, Adam

216

Codon conservation in the influenza A virus genome defines RNA packaging signals  

Microsoft Academic Search

Genome segmentation facilitates reassortment and rapid evolution of influenza A virus. However, segmentation complicates particle assembly as virions must contain all eight vRNA species to be infectious. Specific packaging signals exist that extend into the coding regions of most if not all segments, but these RNA motifs are poorly defined. We measured codon variability in a large dataset of sequences

Julia R. Gog; Emmanuel Dos Santos Afonso; Rosa M. Dalton; India Leclercq; Laurence Tiley; Debra Elton; Johann C. von Kirchbach; Nadia Naffakh; Nicolas Escriou; Paul Digard

2007-01-01

217

Expanded use of sense codons is regulated by modified cytidines in tRNA  

PubMed Central

Codon use among the three domains of life is not confined to the universal genetic code. With only 22 tRNA genes in mammalian mitochondria, exceptions from the universal code are necessary for proper translation. A particularly interesting deviation is the decoding of the isoleucine AUA codon as methionine by the one mitochondrial-encoded tRNAMet. This tRNA decodes AUA and AUG in both the A- and P-sites of the metazoan mitochondrial ribosome. Enrichment of posttranscriptional modifications is a commonly appropriated mechanism for modulating decoding rules, enabling some tRNA functions while restraining others. In this case, a modification of cytidine, 5-formylcytidine (f5C), at the wobble position-34 of human mitochondrial () enables expanded decoding of AUA, resulting in a deviation in the genetic code. Visualization of the codon•anticodon interaction by X-ray crystallography revealed that recognition of both A and G at the third position of the codon occurs in the canonical Watson–Crick geometry. A modification-dependent shift in the tautomeric equilibrium toward the rare imino-oxo tautomer of cytidine stabilizes the f5C34•A base pair geometry with two hydrogen bonds. PMID:23781103

Cantara, William A.; Murphy, Frank V.; Demirci, Hasan; Agris, Paul F.

2013-01-01

218

Enhanced expression of the codon-optimized exo-inulinase gene from the yeast Meyerozyma guilliermondii in Saccharomyces sp. W0 and bioethanol production from inulin.  

PubMed

In the present study, after the exo-inulinase gene INU1 from Meyerozyma guilliermondii was optimized according to the codon usage bias of Saccharomyces cerevisiae, both the optimized gene INU1Y and the native gene INU1 were ligated into the homologous integration expression vector pMIRSC11 and expressed in Saccharomyces sp. W0. It was determined that the inulinase activity of the recombinant yeast Y13 with the optimized gene INU1Y was 43.84 U/mL, which was obviously higher than that (31.39 U/mL) produced by the recombinant yeast EX3 with the native gene INU1. Moreover, it was indicated that the recombinant yeast Y13 could produce 126.30 mg/mL ethanol from 300.0 g/L inulin while the recombinant yeast EX3 and Saccharomyces sp. W0 produced 122.75 mg/mL and 114.15 mg/mL ethanol, respectively, under the same conditions. In addition, the ethanol productivity of the recombinant yeast Y13 was 2.25 mg/mL/h within 48 h of the fermentation, which was obviously higher than that of the recombinant yeast EX3 (1.97 mg/mL/h) and Saccharomyces sp. W0 (1.77 mg/mL/h) within the same period. The results demonstrated that the recombinant yeast Y13 had higher ethanol production and productivity than the recombinant yeast EX3 and Saccharomyces sp. W0. Therefore, it was concluded that the codon optimization of the exo-inulinase gene from M. guilliermondii effectively enhanced inulinase activity and improved ethanol production from inulin by Saccharomyces sp. W0 carrying the optimized inulinase gene. PMID:25236803

Liu, Guang-Lei; Fu, Ge-Yi; Chi, Zhe; Chi, Zhen-Ming

2014-11-01

219

TrimerDimer: an oligonucleotide-based saturation mutagenesis approach that removes redundant and stop codons  

PubMed Central

9-fluorenylmethoxycarbonyl (Fmoc) and 4,4?-dimethoxytrityl (DMTr) are orthogonal hydroxyl protecting groups that have been used in conjunction to assemble oligonucleotide libraries whose variants contain wild-type and mutant codons randomly interspersed throughout a focused DNA region. Fmoc is labile to organic bases and stable to weak acids, whereas DMTr behaves oppositely. Based on these chemical characteristics, we have now devised TrimerDimer, a novel codon-based saturation mutagenesis approach that removes redundant and stop codons during the assembly of degenerate oligonucleotides. In this approach, five DMTr-protected trinucleotide phosphoramidites (dTGG, dATG, dTTT, dTAT and dTGC) and five Fmoc-protected dinucleotide phosphoramidites (dAA, dTT, dAT, dGC and dCG) react simultaneously with a starting oligonucleotide growing on a solid support. The Fmoc group is then removed and the incorporated dimers react with a mixture of three DMTr-protected monomer phosphoramidites (dC, dA and dG) to produce 15 trinucleotides: dCAA, dAAA, dGAA, dCTT, dATT, dGTT, dCAT, dAAT, dGAT, dCGC, dAGC, dGGC, dCCG, dACG and dGCG. After one mutagenic cycle, 20 codons are generated encoding the 20 natural amino acids. TrimerDimer was tested by randomizing the four contiguous codons that encode amino acids L64–G67 of an engineered, nonfluorescent GFP protein. Sequencing of 89 nonfluorescent mutant clones and isolation of two fluorescent mutants confirmed the principle. PMID:19783828

Gaytan, Paul; Contreras-Zambrano, Casandra; Ortiz-Alvarado, Monica; Morales-Pablos, Alfredo; Yanez, Jorge

2009-01-01

220

p53 codon 72 polymorphism and human papillomavirus associated skin cancer  

PubMed Central

Background/Aims—Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC. Methods—Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV. Results—The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant differences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts. Conclusions—These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer. Key Words: p53 codon 72 polymorphism • human papillomavirus • skin cancer PMID:11429426

O'Connor, D; Kay, E; Leader, M; Atkins, G; Murphy, G; Mabruk, M

2001-01-01

221

47 CFR 22.907 - Coordination of channel usage.  

Code of Federal Regulations, 2010 CFR

... false Coordination of channel usage. 22.907 Section...Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED...22.907 Coordination of channel usage. Licensees in...with the appropriate parties, channel usage at each...

2010-10-01

222

Understanding Road Usage Patterns in Urban Areas  

PubMed Central

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach. PMID:23259045

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; Gonzalez, Marta C.

2012-01-01

223

INTRODUCTION Measurements of actual spectrum usage have  

E-print Network

INTRODUCTION Measurements of actual spectrum usage have revealed the pervasiveness of idle observed. These measurements highlight the drawbacks of the current static spectrum allotment policy in conventional wired or wire- less networks. To protect spectrum licensees from interference while providing

Zhao, Qing

224

College Student Credit Card Usage and Debt.  

ERIC Educational Resources Information Center

Provides an overview of the concerns related to credit card usage by college students. Offers information student affairs professionals can use to help college students make responsible choices. (Contains 26 references.) (GCP)

Rybka, Kathryn M.

2001-01-01

225

Understanding Road Usage Patterns in Urban Areas  

NASA Astrophysics Data System (ADS)

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach.

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; González, Marta C.

2012-12-01

226

Understanding road usage patterns in urban areas.  

PubMed

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own--surprisingly few--driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach. PMID:23259045

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M; Schechtner, Katja; González, Marta C

2012-01-01

227

Material impacts on operational energy usage  

E-print Network

Decisions regarding materials and construction of a building are made all the time in the architectural process, but thought is not always given to how those choices may affect the buildings ultimate energy usage and the ...

Love, Andrea, S.M. Massachusetts Institute of Technology

2011-01-01

228

Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data  

Microsoft Academic Search

BACKGROUND: 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

Le Bao; Hong Gu; Katherine A Dunn; Joseph P Bielawski

2007-01-01

229

E-Book Usage and the "Choice" Outstanding Academic Book List: Is There a Correlation?  

ERIC Educational Resources Information Center

In this study, the staff of the library at Auburn University at Montgomery analyzed circulation patterns for electronic books in the fields of Political Science, Public Administration and Law to see if favorable "Choice" reviews can be used to predict usage of electronic books. A comparison of the circulations between print and electronic books…

Carter Williams, Karen; Best, Rickey

2006-01-01

230

Enhanced bacterial expression of several mammalian cytochrome P450s by codon optimization and chaperone coexpression  

PubMed Central

To elucidate the effect of codon optimization and chaperone coexpression on the heterologous expression of mammalian cytochrome P450s in Escherichia coli, the expression of P450s 2B1, 2S1, 2U1, 2W1, and 27C1 were investigated. With codon optimization for N-terminus or the entire gene, the expression levels of P450 27C1, 2U1 and 2W1 increased 22-fold, 3.6-fold and 2.1-fold respectively, while those for P450s 2B1 and 2S1 remained unchanged. With coexpression of E. coli molecular chaperones GroEL/ES, the expression level increased up to 14-fold for P450 27C1, and 3- to 5-fold for P450s 2B1, 2S1, and 2W1. Simultaneous application of these two techniques resulted in synergetic effects. PMID:19557307

Qiao, Jing; Zhang, Zhi-Gang; Guengerich, F. Peter; Liu, Yan; Pei, Xiao-Qiong

2014-01-01

231

Lack of IRS-1 codon 513 and 972 polymorphism in Pima Indians  

SciTech Connect

Insulin receptor substrate-1 (IRS-1), a 1242 amino acid protein, an endogenous substrate for the insulin receptor tyrosine kinase, mediates many or all of the metabolic actions of insulin. Recently, polymorphism at codons 513 and 972 of the IRS-1 gene resulting in 2 amino acid substitutions that were associated with type II diabetes were found in a Caucasian population. Using allele specific oligonucleotide (ASO) hybridization, we screened 242 diabetic and 190 nondiabetic Pima Indians, a population with a very high prevalence of type II diabetes. Neither of the two mutations was present in either diabetic or nondiabetic subjects. We conclude that polymorphism at codons 513 and 972 of the IRS-1 gene observed in certain Caucasian populations is very rare or absent in Pima Indians. 20 refs., 2 figs., 1 tab.

Celi, F.S.; Silver, K.; Walston, J. [and others] [and others

1995-09-01

232

Degradation of mRNAs that lack a stop codon: A decade of nonstop progress  

PubMed Central

Nonstop decay is the mechanism of identifying and disposing aberrant transcripts that lack in-frame stop codons. It is hypothesized that these transcripts are identified during translation when the ribosome arrives at the 3? end of the mRNA and stalls. Presumably the ribosome stalling recruits additional cofactors, Ski7 and the exosome complex. The exosome degrades the transcript using either one of is ribonucleolytic activities and the ribosome and the peptide are both released. Additional precautionary measures by the nonstop decay pathway may include translational repression of the nonstop transcript after translation, and proteolysis of the released peptide by the proteasome. This surveillance mechanism protects the cells from potentially harmful truncated proteins, but it may also be involved in mediating critical cellular functions of transcripts that are prone to stop codon read-through. Important advances have been made in the past decade as we learn that nonstop decay may have implications in human disease. PMID:22740367

Klauer, A. Alejandra; van Hoof, Ambro

2013-01-01

233

Function of 3? non-coding sequences and stop codon usage in expression of the chloroplast psaB gene in Chlamydomonas reinhardtii  

Microsoft Academic Search

The rate of mRNA decay is an important step in the control of gene expression in prokaryotes, eukaryotes and cellular organelles. Factors that determine the rate of mRNA decay in chloroplasts are not well understood. Chloroplast mRNAs typically contain an inverted repeat sequence within the 3' untranslated region that can potentially fold into a stem-loop structure. These stem-loop structures have

Hyeonmoo Lee; Scott E. Bingham; Andrew N. Webber

1996-01-01

234

The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection  

PubMed Central

To elucidate an outline of the mechanism of eukaryotic translation initiation, 48S complex formation was analyzed on defined mRNAs in reactions reconstituted in vitro from fully purified translation components. We found that a ribosomal 40S subunit, eukaryotic initiation factor (eIF) 3, and the eIF2 ternary complex form a 43S complex that can bind to the 5?-end of an unstructured 5?-untranslated region (5?-UTR) and in the presence of eIF1 scan along it and locate the initiation codon without a requirement for adenosine triphosphate (ATP) or factors (eIF4A, eIF4B, eIF4F) associated with ATP hydrolysis. Scanning on unstructured 5?-UTRs was enhanced by ATP, eIFs 4A and 4B, and the central domain of the eIF4G subunit of eIF4F. Their omission increased the dependence of scanning on eIFs 1 and 1A. Ribosomal movement on 5?-UTRs containing even weak secondary structures required ATP and RNA helicases. eIF4F was essential for scanning, and eIFs 4A and 4B were insufficient to promote this process in the absence of eIF4F. We report that in addition to its function in scanning, eIF1 also plays a principal role in initiation codon selection. In the absence of eIF1, 43S complexes could no longer discriminate between cognate and noncognate initiation codons or sense the nucleotide context of initiation codons and were able to assemble 48S complexes on 5?-proximal AUG triplets located only 1, 2, and 4 nt from the 5?-end of mRNA. PMID:12435632

Pestova, Tatyana V.; Kolupaeva, Victoria G.

2002-01-01

235

Aminoglycoside suppression at UAG, UAA and UGA codons in Escherichia coli and human tissue culture cells  

Microsoft Academic Search

Summary  We have compared the suppression of nonsense mutations by aminoglycoside antibiotics inEscherichia coli and in human 293 cells. Six nonsense alleles of the chloramphenicol acetyl transferase (cat) gene, in the vector pRSVcat, were suppressed by growth in G418 and paromomycin. Readthrough at UAG, UAA and UGA codons was monitored with enzyme assays\\u000a for chloramphenicol acetyl transferase (CAT), in stably transformed

Robin Martin; Anne E. Mogg; Louise A. Heywood; Lars Nitschke; Julian F. Burke

1989-01-01

236

Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma.  

PubMed

Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas. PMID:23313955

Harbour, J William; Roberson, Elisha D O; Anbunathan, Hima; Onken, Michael D; Worley, Lori A; Bowcock, Anne M

2013-02-01

237

Glutathione Peroxidase Codon 198 Polymorphism Variant Increases Lung Cancer Risk1  

Microsoft Academic Search

Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-depen- dent enzyme that participates in the detoxification of hydrogen peroxide and a wide range of organic peroxides. We conducted a case-control study nested within the a-Tocopherol, b-Carotene Cancer Prevention Study cohort to evaluate the association between the proline to leucine polymor- phism at codon 198 of hGPX1 and lung cancer risk.

Duminda Ratnasinghe; Joseph A. Tangrea; Mark R. Andersen; Michael J. Barrett; Jarmo Virtamo; Philip R. Taylor; Demetrius Albanes

238

Translation of CGA codon repeats in yeast involves quality control components and ribosomal protein L1.  

PubMed

Translation of CGA codon repeats in the yeast Saccharomyces cerevisiae is inefficient, resulting in dose-dependent reduction in expression and in production of an mRNA cleavage product, indicative of a stalled ribosome. Here, we use genetics and translation inhibitors to understand how ribosomes respond to CGA repeats. We find that CGA codon repeats result in a truncated polypeptide that is targeted for degradation by Ltn1, an E3 ubiquitin ligase involved in nonstop decay, although deletion of LTN1 does not improve expression downstream from CGA repeats. Expression downstream from CGA codons at residue 318, but not at residue 4, is improved by deletion of either ASC1 or HEL2, previously implicated in inhibition of translation by polybasic sequences. Thus, translation of CGA repeats likely causes ribosomes to stall and exploits known quality control systems. Expression downstream from CGA repeats at amino acid 4 is improved by paromomycin, an aminoglycoside that relaxes decoding specificity. Paromomycin has no effect if native tRNA(Arg(ICG)) is highly expressed, consistent with the idea that failure to efficiently decode CGA codons might occur in part due to rejection of the cognate tRNA(Arg(ICG)). Furthermore, expression downstream from CGA repeats is improved by inactivation of RPL1B, one of two genes encoding the universally conserved ribosomal protein L1. The effects of rpl1b-? and of either paromomycin or tRNA(Arg(ICG)) on CGA decoding are additive, suggesting that the rpl1b-? mutant suppresses CGA inhibition by means other than increased acceptance of tRNA(Arg(ICG)). Thus, inefficient decoding of CGA likely involves at least two independent defects in translation. PMID:23825054

Letzring, Daniel P; Wolf, Andrew S; Brule, Christina E; Grayhack, Elizabeth J

2013-09-01

239

Relationship between codon biased genes, microarray expression values and physiological characteristics of Streptococcus pneumoniae  

Microsoft Academic Search

A codon-profile strategy was used to predict gene expression levels in Streptococcus pneumoniae. Predicted highly expressed (PHE) genes included those encoding glycolytic and fermentative enzymes, sugar-conversion systems and carbohydrate-transporters. Additionally, some genes required for infection that are involved in oxidative metabolism and hydrogen peroxide production were PHE. Low expression values were predicted for genes encoding specific regulatory proteins like two-component

Antonio J. Martin-Galiano; Jerry M. Wells; Adela G. de la Campa

2004-01-01

240

Effect of codon optimisation on the production of recombinant fish growth hormone in Pichia pastoris.  

PubMed

This study was established to test the hypothesis of whether the codon optimization of fish growth hormone gene (FGH) based on P. pastoris preferred codon will improve the quantity of secreted rFGH in culture supernatant that can directly be used as fish feed supplements. The optimized FGH coding sequence (oFGH) and native sequence (nFGH) of giant grouper fish (Epinephelus lanceolatus) were cloned into P. pastoris expression vector (pPICZ?A) downstream of alcohol oxidase gene (AOX1) for efficient induction of extracellular rFGH by adding 1% of absolute methanol. The results showed that recombinant P. pastoris was able to produce 2.80 ± 0.27 mg of oFGH compared to 1.75 ± 0.25 of nFGH in one litre of culture supernatant. The total body weight of tiger grouper fingerlings fed with oFGH increased significantly at third (P < 0.05) and fourth weeks (P < 0.01) of four-week experiment period compared to those fed with nFGH. Both oFGH and nFGH significantly enhanced the final biomass and fish survival percentage. In conclusion, codon optimization of FGH fragment was useful to increase rFGH quantity in the culture supernatant of P. pastoris that can be directly used as fish feed supplements. Further studies are still required for large scale production of rFGH and practical application in aquaculture production. PMID:25147851

Rothan, Hussin A; Huy, Teh Ser; Mohamed, Zulqarnain

2014-01-01

241

Structural Changes Enable Start Codon Recognition by the Eukaryotic Translation Initiation Complex  

PubMed Central

Summary During eukaryotic translation initiation, initiator tRNA does not insert fully into the P decoding site on the 40S ribosomal subunit. This conformation (POUT) is compatible with scanning mRNA for the AUG start codon. Base pairing with AUG is thought to promote isomerization to a more stable conformation (PIN) that arrests scanning and promotes dissociation of eIF1 from the 40S subunit. Here, we present a cryoEM reconstruction of a yeast preinitiation complex at 4.0 Å resolution with initiator tRNA in the PIN state, prior to eIF1 release. The structure reveals stabilization of the codon-anticodon duplex by the N-terminal tail of eIF1A, changes in the structure of eIF1 likely instrumental in its subsequent release, and changes in the conformation of eIF2. The mRNA traverses the entire mRNA cleft and makes connections to the regulatory domain of eIF2?, eIF1A, and ribosomal elements that allow recognition of context nucleotides surrounding the AUG codon.

Hussain, Tanweer; Llácer, Jose L.; Fernández, Israel S.; Munoz, Antonio; Martin-Marcos, Pilar; Savva, Christos G.; Lorsch, Jon R.; Hinnebusch, Alan G.; Ramakrishnan, V.

2014-01-01

242

Codon insertion and deletion functions as a somatic diversification mechanism in human antibody repertoires  

PubMed Central

It has been suggested that codon insertion and/or deletion may represent a mechanism that, along with hypermutation, contributes to the affinity maturation of antibodies. We used repertoire cloning to examine human antibodies directed against 3 carbohydrate antigens and 1 protein antigen for the presence of such modifications. We find that both the insertion and deletion of codons occur frequently in antigen-specific responses following vaccination. Codon insertions and deletions were observed most often in the complementarity determining regions, and less frequently in the framework regions, of VH, V?, and V? gene segments, and involved motifs known to be preferred targets of somatic hypermutation. Clonal lineage analysis shows that these events occur through out the course of the somatic maturation of individual antibody clones. We also determined that these alterations of paratope structure have varying effects on the relative affinity of the binding site for its cognate antigen. Reviewers This article was reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein. Open peer review Reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein. For the full reviews, please go to the Reviewers' comments section. PMID:16942619

Reason, Donald C; Zhou, Jianhui

2006-01-01

243

Codon optimization significantly improves the expression level of a keratinase gene in Pichia pastoris.  

PubMed

The main keratinase (kerA) gene from the Bacillus licheniformis S90 was optimized by two codon optimization strategies and expressed in Pichia pastoris in order to improve the enzyme production compared to the preparations with the native kerA gene. The results showed that the corresponding mutations (synonymous codons) according to the codon bias in Pichia pastoris were successfully introduced into keratinase gene. The highest keratinase activity produced by P. pastoris pPICZ?A-kerAwt, pPICZ?A-kerAopti1 and pPICZ?A-kerAopti2 was 195 U/ml, 324 U/ml and 293 U/ml respectively. In addition, there was no significant difference in biomass concentration, target gene copy numbers and relative mRNA expression levels of every positive strain. The molecular weight of keratinase secreted by recombinant P. pastori was approx. 39 kDa. It was optimally active at pH 7.5 and 50°C. The recombinant keratinase could efficiently degrade both ?-keratin (keratin azure) and ?-keratin (chicken feather meal). These properties make the P. pastoris pPICZ?A-kerAopti1 a suitable candidate for industrial production of keratinases. PMID:23472192

Hu, Hong; Gao, Jie; He, Jun; Yu, Bing; Zheng, Ping; Huang, Zhiqing; Mao, Xiangbing; Yu, Jie; Han, Guoquan; Chen, Daiwen

2013-01-01

244

Codon Optimization Significantly Improves the Expression Level of a Keratinase Gene in Pichia pastoris  

PubMed Central

The main keratinase (kerA) gene from the Bacillus licheniformis S90 was optimized by two codon optimization strategies and expressed in Pichia pastoris in order to improve the enzyme production compared to the preparations with the native kerA gene. The results showed that the corresponding mutations (synonymous codons) according to the codon bias in Pichia pastoris were successfully introduced into keratinase gene. The highest keratinase activity produced by P. pastoris pPICZ?A-kerAwt, pPICZ?A-kerAopti1 and pPICZ?A-kerAopti2 was 195 U/ml, 324 U/ml and 293 U/ml respectively. In addition, there was no significant difference in biomass concentration, target gene copy numbers and relative mRNA expression levels of every positive strain. The molecular weight of keratinase secreted by recombinant P. pastori was approx. 39 kDa. It was optimally active at pH 7.5 and 50°C. The recombinant keratinase could efficiently degrade both ?-keratin (keratin azure) and ?-keratin (chicken feather meal). These properties make the P. pastoris pPICZ?A-kerAopti1 a suitable candidate for industrial production of keratinases. PMID:23472192

Hu, Hong; Gao, Jie; He, Jun; Yu, Bing; Zheng, Ping; Huang, Zhiqing; Mao, Xiangbing; Yu, Jie; Han, Guoquan; Chen, Daiwen

2013-01-01

245

Analysis of PRNP gene codon 129 polymorphism in the Greek population.  

PubMed

Creutzfeldt-Jakob disease (CJD) is a fatal transmissible neurodegenerative prion disease with a rapid progression comprising familial, sporadic, iatrogenic and variant forms. A polymorphism at codon 129 of PRNP gene has been implicated in the development of variant CJD. We examined Met/Val allele frequencies and the genotype distribution, with respect to the polymorphic codon 129 of PRNP gene in 348 healthy individuals from the region of Athens, Greece. The following genotype frequencies were observed in the Greek population: Met/Met 50%, Met/Val 39% and Val/Val 11%. The presence of the Methionine allele frequencies in various European populations, according to the published data, increases gradually from northwestern to southeastern countries, implying the presence of a cline. The distribution of genotypes of Met homozygotes displays random declination across the 10 compared populations. The observed higher frequency of Met homozygotes at codon 129 does not necessarily suggest that these populations are at increased risk of developing CJD. PMID:16547836

Saetta, Angelica A; Michalopoulos, Nikolaos V; Malamis, George; Papanastasiou, Polyanthi I; Mazmanian, Niki; Karlou, Maria; Kouzoupis, Anastasios; Korkolopoulou, Penelope; Patsouris, Efstratios

2006-01-01

246

Codon-based phylogenetics introduces novel flagellar gene markers to oomycete systematics.  

PubMed

Oomycete systematics has traditionally been reliant on ribosomal RNA and mitochondrial cytochrome oxidase sequences. Here we report the use of two single-copy protein-coding flagellar genes, PF16 and OCM1, in oomycete systematics, showing their utility in phylogenetic reconstruction and species identification. Applying a recently proposed mutation-selection model of codon substitution, the phylogenetic relationships inferred by flagellar genes are largely in agreement with the current views of oomycete evolution, whereas nucleotide- and amino acid-level models produce biologically implausible reconstructions. Interesting parallels exist between the phylogeny inferred from the flagellar genes and zoospore ontology, providing external support for the tree obtained using the codon model. The resolution achieved for species identification is ample using PF16, and quite robust using OCM1, and the described PCR primers are able to amplify both genes for a range of oomycete genera. Altogether, when analyzed with a rich codon substitution model, these flagellar genes provide useful markers for the oomycete molecular toolbox. PMID:24747002

Robideau, Gregg P; Rodrigue, Nicolas; André Lévesque, C

2014-10-01

247

Relationship between p53 gene codon-72 polymorphisms and hypertrophic scar formation following caesarean section  

PubMed Central

The aim of the present study was to determine the relationship between p53 gene codon-72 polymorphisms and hypertrophic scar formation following caesarean section (CS). Blood samples from 260 female patients were collected one week following a CS for the detection of p53 gene polymorphisms using a molecular beacon-coupled quantitative polymerase chain reaction technique. Patients had follow-ups for 12–18 months to observe the scar formation. From these observations, the relationship between the p53 codon-72 polymorphisms and hypertrophic scar formation occurrence was investigated. Among the patients with the CCC/CCC genotype, nine patients had hypertrophic scars and 46 patients showed normal healing, which is a ratio of 0.19. However, the follow-up investigations indicated that the presence of a homozygous or heterozygous C-to-G alteration at the codon-72 site in gene p53 resulted in 13 patients with hypertrophic scars and 192 patients with normal healing, which is a ratio of 0.07. Therefore, these results indicate that patients with the CCC/CCC genotype had a higher risk of developing hypertrophic scars compared with that for patients with the CCC/CGC or CGC/CGC genotypes. PMID:24940419

GAO, JIANHUA; CHEN, YING; LIAO, NONG; ZHAO, WEI; ZENG, WEISEN; LI, YINGTAO; WANG, SHAOJING; LU, FENG

2014-01-01

248

JSTOR usage data and what it can tell us about ourselves: is there predictability based on historical use by libraries of similar size?  

Microsoft Academic Search

Purpose – Sets out to explore what effects institutional size and the selections of JSTOR collections have on the overall (total) usage statistics. Design\\/methodology\\/approach – This is a preliminary report of JSTOR use made by five academic libraries of similar size and scale; a sixth smaller campus is used to contrast\\/support findings. A comparison study of the five institutions' usage

Barbara J. Gauger; Carolyn Kacena

2006-01-01

249

Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds  

PubMed Central

PrP genotypes at codons 136 and 171 in 120 Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated. PMID:21778818

Zadeh, Reza Ashrafi; Omrani, Mir Davood; Ramezani, Fatemeh; Amniattalab, Amir

2011-01-01

250

Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds.  

PubMed

PrP genotypes at codons 136 and 171 in one hundred twenty Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States, and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated. PMID:21778818

Salami, Siamak; Zadeh, Reza Ashrafi; Omrani, Mir Davood; Ramezani, Fatemeh; Amniattalab, Amir

2011-01-01

251

Near-cognate suppression of amber, opal and quadruplet codons competes with aminoacyl-tRNAPyl for genetic code expansion  

PubMed Central

Over 300 amino acids are found in proteins in nature, yet typically only 20 are genetically encoded. Reassigning stop codons and use of quadruplet codons emerged as the main avenues for genetically encoding non-canonical amino acids (NCAAs). Canonical aminoacyl-tRNAs with near-cognate anticodons also read these codons to some extent. This background suppression leads to ‘statistical protein’ that contains some natural amino acid(s) at a site intended for NCAA. We characterize near-cognate suppression of amber, opal and a quadruplet codon in common Escherichia coli laboratory strains and find that the PylRS/tRNAPyl orthogonal pair cannot completely outcompete contamination by natural amino acids. PMID:23036644

O’Donoghue, Patrick; Prat, Laure; Heinemann, Ilka U.; Ling, Jiqiang; Odoi, Keturah; Liu, Wenshe R.; Söll, Dieter

2012-01-01

252

Apolipoprotein B48 is the Product of a Messenger RNA with an Organ-Specific In-Frame Stop Codon  

Microsoft Academic Search

The primary structure of human apolipoprotein (apo) B-48 has been deduced and shown by a combination of DNA excess hybridization, sequencing of tryptic peptides, cloned complementary DNAs, and intestinal messenger RNAs (mRNAs) to be the product of an intestinal mRNA with an in-frame UAA stop codon resulting from a C to U change in the codon CAA encoding Gln2153 in

San-Hwan Chen; Geetha Habib; Chao-Yuh Yang; Zi-Wei Gu; Bo Rong Lee; Shi-Ai Weng; Steven R. Silberman; Sheng-Jian Cai; J. P. Deslypere; Maryvonne Rosseneu; Antonio M. Gotto; Wen-Hsiung Li; Lawrence Chan

1987-01-01

253

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

PubMed Central

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (?GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an ‘accessory’ during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. PMID:25200075

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

2014-01-01

254

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

PubMed Central

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

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

2013-01-01

255

Convergence and constraint in eukaryotic release factor 1 (eRF1) domain 1: the evolution of stop codon specificity  

PubMed Central

Class 1 release factor in eukaryotes (eRF1) recognizes stop codons and promotes peptide release from the ribosome. The ‘molecular mimicry’ hypothesis suggests that domain 1 of eRF1 is analogous to the tRNA anticodon stem–loop. Recent studies strongly support this hypothesis and several models for specific interactions between stop codons and residues in domain 1 have been proposed. In this study we have sequenced and identified novel eRF1 sequences across a wide diversity of eukaryotes and re-evaluated the codon-binding site by bioinformatic analyses of a large eRF1 dataset. Analyses of the eRF1 structure combined with estimates of evolutionary rates at amino acid sites allow us to define the residues that are under structural (i.e. those involved in intramolecular interactions) versus non-structural selective constraints. Furthermore, we have re-assessed convergent substitutions in the ciliate variant code eRF1s using maximum likelihood-based phylogenetic approaches. Our results favor the model proposed by Bertram et al. that stop codons bind to three ‘cavities’ on the protein surface, although we suggest that the stop codon may bind in the opposite orientation to the original model. We assess the feasibility of this alternative binding orientation with a triplet stop codon and the eRF1 domain 1 structures using molecular modeling techniques. PMID:11788716

Inagaki, Yuji; Blouin, Christian; Doolittle, W. Ford; Roger, Andrew J.

2002-01-01

256

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

PubMed

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (?GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. PMID:25200075

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

2015-01-01

257

Motivations and usage patterns of Weibo.  

PubMed

Referred to as "Weibo," microblogging in China has witnessed an exponential growth. In addition to the Twitter-like functionality, Weibo allows rich media uploads into user feeds, provides threaded comments, and offers applications, games, and Weibo medals. This expanded functionality, as well as the observed differences in trending content, suggests potentially different user motivations to join Weibo and their usage patterns compared to Twitter. This pioneering study identifies dominant Weibo user motivations and their effects on usage patterns. We discuss the findings of an online survey of 234 Weibo users and suggest managerial implications and future research directions. PMID:22703037

Zhang, Lixuan; Pentina, Iryna

2012-06-01

258

Context-dependent codon partition models provide significant increases in model fit in atpB and rbcL protein-coding genes  

PubMed Central

Background Accurate modelling of substitution processes in protein-coding sequences is often hampered by the computational burdens associated with full codon models. Lately, codon partition models have been proposed as a viable alternative, mimicking the substitution behaviour of codon models at a low computational cost. Such codon partition models however impose independent evolution of the different codon positions, which is overly restrictive from a biological point of view. Given that empirical research has provided indications of context-dependent substitution patterns at four-fold degenerate sites, we take those indications into account in this paper. Results We present so-called context-dependent codon partition models to assess previous empirical claims that the evolution of four-fold degenerate sites is strongly dependent on the composition of its two flanking bases. To this end, we have estimated and compared various existing independent models, codon models, codon partition models and context-dependent codon partition models for the atpB and rbcL genes of the chloroplast genome, which are frequently used in plant systematics. Such context-dependent codon partition models employ a full dependency scheme for four-fold degenerate sites, whilst maintaining the independence assumption for the first and second codon positions. Conclusions We show that, both in the atpB and rbcL alignments of a collection of land plants, these context-dependent codon partition models significantly improve model fit over existing codon partition models. Using Bayes factors based on thermodynamic integration, we show that in both datasets the same context-dependent codon partition model yields the largest increase in model fit compared to an independent evolutionary model. Context-dependent codon partition models hence perform closer to codon models, which remain the best performing models at a drastically increased computational cost, compared to codon partition models, but remain computationally interesting alternatives to codon models. Finally, we observe that the substitution patterns in both datasets are drastically different, leading to the conclusion that combined analysis of these two genes using a single model may not be advisable from a context-dependent point of view. PMID:21619569

2011-01-01

259

Individuals' Decision to Co-Donate or Donate Alone: An Archival Study of Married Whole Body Donors in Hawaii  

PubMed Central

Background Human cadavers are crucial to numerous aspects of health care, including initial and continuing training of medical doctors and advancement of medical research. Concerns have periodically been raised about the limited number of whole body donations. Little is known, however, about a unique form of donation, namely co-donations or instances when married individuals decide to register at the same time as their spouse as whole body donors. Our study aims to determine the extent of whole body co-donation and individual factors that might influence co-donation. Methods and Findings We reviewed all records of registrants to the University of Hawaii Medical School’s whole body donation program from 1967 through 2006 to identify married registrants. We then examined the 806 married individuals’ characteristics to understand their decision to register alone or with their spouse. We found that married individuals who registered at the same time as their spouse accounted for 38.2 percent of married registrants. Sex differences provided an initial lens to understand co-donation. Wives were more likely to co-donate than to register alone (p?=?0.002). Moreover, registrants’ main occupational background had a significant effect on co-donations (p?=?0.001). Married registrants (regardless of sex) in female-gendered occupations were more likely to co-donate than to donate alone (p?=?0.014). Female-gendered occupations were defined as ones in which women represented more than 55 percent of the workforce (e.g., preschool teachers). Thus, variations in donors’ occupational backgrounds explained co-donation above and beyond sex differences. Conclusions Efforts to secure whole body donations have historically focused on individual donations regardless of donors’ marital status. More attention needs to be paid, however, to co-donations since they represent a non-trivial number of total donations. Also, targeted outreach efforts to male and female members of female-gendered occupations might prove a successful way to increase donations through co-donations. PMID:22880077

Anteby, Michel; Garip, Filiz; Martorana, Paul V.; Lozanoff, Scott

2012-01-01

260

Female Athletes and Performance-Enhancer Usage  

ERIC Educational Resources Information Center

The purpose of this study was to develop a knowledge base on factors associated with performance-enhancer usage among female athletes at the high school level in order to identify markers for a future prevention-education program. The study used a pretest-only, between-subjects Likert Scale survey to rank the importance of internal and external…

Fralinger, Barbara K.; Pinto-Zipp, Genevieve; Olson, Valerie; Simpkins, Susan

2007-01-01

261

Jadeite: Improving API Documentation Using Usage Information  

E-print Network

Jadeite: Improving API Documentation Using Usage Information Abstract Jadeite is a new Javadoc-like API documentation sys- tem that takes advantage of multiple users' aggregate experience to reduce difficulties that programmers have learning new APIs. Previous studies have shown that programmers often

Myers, Brad A.

262

Predicting Student Success via Online Homework Usage  

ERIC Educational Resources Information Center

With the amount of data available through an online homework system about students' study habits, it stands to reason that such systems can be used to identify likely student outcomes. A study was conducted to see how student usage of an online chemistry homework system (OWL) correlated with student success in a general chemistry course.…

Bowman, Charles R.; Gulacar, Ozcan; King, Daniel B.

2014-01-01

263

Worldwide patterns of combination drug usage  

Microsoft Academic Search

Two related and interlocking spheres of activity with respect to combination drugs, the sphere of theoretical debate and the sphere of actual use, must be considered. Debate and learned opinion serves to strengthen the scientific basis for the development and prescribing of combination drugs. Physician preferences and actual usage patterns around the world, among both specialists and general practitioners, show

W. H. Helfand

1979-01-01

264

Drug Usage Trends Among College Students  

ERIC Educational Resources Information Center

The health Education Department of the University of Maryland continuously monitors the drug usage trends on campus. The latest survey (fall, 1973) of 1,385 undergraduates at this school shows that student use of illicit drugs has increased. Alcohol is the most popular drug followed by marijuana, hashish, methaqualone and speed. (Author)

Girdano, Daniel A.; Girdano, Dorothy Dusek

1974-01-01

265

Measuring Computer Usage in a College Setting.  

ERIC Educational Resources Information Center

In spring 1998, a total of 452 students in 49 selected classes and 44% of faculty at Johnson County Community College returned surveys assessing respondents' computer usage and future computer needs. Results indicate a trend toward greater utilization of computers in education. (Contains nine references.) (PGS)

Coklin, Karen A.

1999-01-01

266

Bicycle Safety Helmet Usage In Berlin 1999  

E-print Network

#12;Qualitative Literature Review · outcome: head injury · target population: children · epidemiologic: head injury · target population: children · epidemiologic measure: RR (helmet usage) · year: 93 popular in the big cities in Europe and USA · 1/3 of all bicycle accidents involve head injuries · 3

Boehning, Dankmar

267

Recent Developments in Web Usage Mining Research  

Microsoft Academic Search

Web Usage Mining is that area of Web Mining which deals with the extraction of interesting knowledge from logging information produced by web servers. In this paper, we present a survey of the recent developments in this area that is receiving increasing attention from the Data Mining community. Web Mining (29) is that area of Data Mining which deals with

Federico Michele Facca; Pier Luca Lanzi

2003-01-01

268

College Student Performance and Credit Card Usage.  

ERIC Educational Resources Information Center

Examines the relationship between credit card usage, employment, and academic performance among a group of college students with credit cards. Results reveal that the students differed significantly in the level of anxiety felt from carrying debt, perceived need to work, and perceived impact of employment on academic performance. (Contains 57…

Pinto, Mary Beth; Parente, Diane H.; Palmer, Todd Starr

2001-01-01

269

Google Scholar Usage: An Academic Library's Experience  

ERIC Educational Resources Information Center

Google Scholar is a free service that provides a simple way to broadly search for scholarly works and to connect patrons with the resources libraries provide. The researchers in this study analyzed Google Scholar usage data from 2006 for three library tools at San Francisco State University: SFX link resolver, Web Access Management proxy server,…

Wang, Ya; Howard, Pamela

2012-01-01

270

GENERIC USAGE MONITORING OF PROGRAMMING STUDENTS  

Microsoft Academic Search

It is becoming feasible and practical to monitor the generic computer usage of students for extended periods, recording low level actions such as mouse clicks, typing and window changes. This paper presents a case study on the deployment of GRUMPS technology during a period of six weeks when 4.7 million such actions were collected from 141 first year university students

Richard Thomas; Gregor E. Kennedy; Steve Draper; Rebecca Mancy; Murray Crease; Huw Evans; Phil Gray

2003-01-01

271

Systematic Stereotype Usage Colin Atkinson1  

E-print Network

Systematic Stereotype Usage Colin Atkinson1 , Thomas K¨uhne2 , and Brian Henderson-Sellers3 1's ability to serve a wide and growing base of users. However, the precise meaning of stereotypes. Two basic ways of using UML stereotypes have been observed in practice: one to support

Kühne, Thomas

272

Nutritional supplements usage by Portuguese athletes.  

PubMed

In this study, we determined the prevalence of nutritional supplements (NS) usage, the type of supplements used, the reasons for usage, and the source of nutritional advice among Portuguese athletes. Two hundred ninety-two athletes (68 % male, 12 - 37 years old) from 13 national sports federations completed a questionnaire that sought information on socio-demographics, sports data, and NS usage. Most athletes (66 %) consumed NS, with a median consumption of 4 supplements per athlete. The most popular supplements included multivitamins/minerals (67 %), sport drinks (62 %), and magnesium (53 %). Significant differences for the type of NS consumed were found between gender and age groups and the number of weekly training hours. Most athletes used NS to accelerate recovery (63 %), improve sports performance (62 %), and have more energy/reduce fatigue (60 %). Athletes sought advice on supplementation mainly from physicians (56 %) and coaches (46 %). Age and gender were found to influence reasons for use and the source of information. Reasons for NS usage were supported scientifically in some cases (e. g., muscle gain upon protein supplementation), but others did not have a scientific basis (e. g., use of glutamine and magnesium). Given the high percentage of NS users, there is an urgent need to provide athletes with education and access to scientific and unbiased information, so that athletes can make assertive and rational choices about the utilization of these products. PMID:24220164

Sousa, Mónica; Fernandes, Maria João; Moreira, Pedro; Teixeira, Vítor Hugo

2013-01-01

273

Production, Usage, and Comprehension in Animal Vocalizations  

ERIC Educational Resources Information Center

In this review, we place equal emphasis on production, usage, and comprehension because these components of communication may exhibit different developmental trajectories and be affected by different neural mechanisms. In the animal kingdom generally, learned, flexible vocal production is rare, appearing in only a few orders of birds and few…

Seyfarth, Robert M.; Cheney, Dorothy L.

2010-01-01

274

Style and Usage Software: Mentor, not Judge.  

ERIC Educational Resources Information Center

Computer software style and usage checkers can encourage students' recursive revision strategies. For example, HOMER is based on the revision pedagogy presented in Richard Lanham's "Revising Prose," while Grammatik II focuses on readability, passive voice, and possibly misused words or phrases. Writer's Workbench "Style" (a UNIX program) provides…

Smye, Randy

275

Identification of TTA codon containing genes in Frankia and exploration of the role of tRNA in regulating these genes.  

PubMed

The TTA codon, one of the six available codons for the amino acid leucine, is the rarest codon among the high GC genomes of Actinobacteria including Frankia. This codon has been implicated in various regulatory mechanisms involving secondary metabolism and morphological development. TTA-mediated gene regulation is well documented in Streptomyces coelicolor, but that role has not been investigated in other Actinobacteria including Frankia. Among the various Actinomycetes with a GC content of more than 70%, Frankia genomes had the highest percentages of TTA-containing genes ranging from 5.2 to 10.68% of the genome. In contrast, TTA-bearing genes comprised 1.7, 3.4 and 4.1% of the Streptomyces coelicolor, S. avermitilis and Nocardia farcinia genomes, respectively. We analyzed their functional role, evolutionary significance, horizontal acquisition and the codon-anticodon interaction. The TTA-bearing genes were found to be well represented in metabolic genes involved in amino acid transport and secondary metabolism. A reciprocal Blast search reveal that many of the TTA-bearing genes have orthologs in the other Frankia genomes, and some of these orthologous genes also have a TTA codon in them. The gene expression level of TTA-containing genes was estimated by the use of the codon adaption index (CAI), and the CAI values were found to have a positive correlation with the GC3 (GC content at the 3rd codon position). A full-atomic 3D model of the leucine tRNA recognizing the TTA (UUA) codon was generated and utilized for in silico docking to determine binding affinity in codon-anticodon interaction. We found a proficient codon-anticodon interaction for this codon which is perhaps why so many genes hold on to this rare codon without compromising their translational efficiency. PMID:21773800

Sen, Arnab; Thakur, Subarna; Bothra, Asim K; Sur, Saubashya; Tisa, Louis S

2012-01-01

276

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

PubMed Central

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

Wang, Pei; Song, Fan; Cai, Wanzhi

2014-01-01

277

Attenuation of human respiratory syncytial virus by genome-scale codon-pair deoptimization.  

PubMed

Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory-tract disease worldwide. A vaccine or generally effective antiviral drug is not yet available. We designed new live attenuated RSV vaccine candidates by codon-pair deoptimization (CPD). Specifically, viral ORFs were recoded by rearranging existing synonymous codons to increase the content of underrepresented codon pairs. Amino acid coding was completely unchanged. Four CPD RSV genomes were designed in which the indicated ORFs were recoded: Min A (NS1, NS2, N, P, M, and SH), Min B (G and F), Min L (L), and Min FLC (all ORFs except M2-1 and M2-2). Surprisingly, the recombinant CPD viruses were temperature-sensitive for replication in vitro (level of sensitivity: Min FLC > Min L > Min B > Min A). All of the CPD mutants grew less efficiently in vitro than recombinant wild-type (WT) RSV, even at the typically permissive temperature of 32 °C (growth efficiency: WT > Min L > Min A > Min FLC > Min B). CPD of the ORFs for the G and F surface glycoproteins provided the greatest restrictive effect. The CPD viruses exhibited a range of restriction in mice and African green monkeys comparable with that of two attenuated RSV strains presently in clinical trials. This study provided a new type of attenuated RSV and showed that CPD can rapidly generate vaccine candidates against nonsegmented negative-strand RNA viruses, a large and expanding group that includes numerous pathogens of humans and animals. PMID:25157129

Le Nouën, Cyril; Brock, Linda G; Luongo, Cindy; McCarty, Thomas; Yang, Lijuan; Mehedi, Masfique; Wimmer, Eckard; Mueller, Steffen; Collins, Peter L; Buchholz, Ursula J; DiNapoli, Joshua M

2014-09-01

278

Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression.  

PubMed

High-throughput screening (HTS) assays used in drug discovery frequently use reporter enzymes such as firefly luciferase (FLuc) as indicators of target activity. An important caveat to consider, however, is that compounds can directly affect the reporter, leading to nonspecific but highly reproducible assay signal modulation. In rare cases, this activity appears counterintuitive; for example, some FLuc inhibitors, acting through posttranslational Fluc reporter stabilization, appear to activate gene expression. Previous efforts to characterize molecules that influence luciferase activity identified a subset of 3,5-diaryl-oxadiazole-containing compounds as FLuc inhibitors. Here, we evaluate a number of compounds with this structural motif for activity against FLuc. One such compound is PTC124 {3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid}, a molecule originally identified in a cell-based FLuc assay as having nonsense codon suppression activity [Welch EM, et al., Nature (2007) 447:87-91]. We find that the potency of FLuc inhibition for the tested compounds strictly correlates with their activity in a FLuc reporter cell-based nonsense codon assay, with PTC124 emerging as the most potent FLuc inhibitor (IC(50) = 7 +/- 1 nM). However, these compounds, including PTC124, fail to show nonsense codon suppression activity when Renilla reniformis luciferase (RLuc) is used as a reporter and are inactive against the RLuc enzyme. This suggests that the initial discovery of PTC124 may have been biased by its direct effect on the FLuc reporter, implicating firefly luciferase as a molecular target of PTC124. Our results demonstrate the value of understanding potential interactions between reporter enzymes and chemical compounds and emphasize the importance of implementing the appropriate control assays before interpreting HTS results. PMID:19208811

Auld, Douglas S; Thorne, Natasha; Maguire, William F; Inglese, James

2009-03-01

279

EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas.  

PubMed

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic "hit" in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways. PMID:22194861

Ryan, Russell J H; Nitta, Mai; Borger, Darrell; Zukerberg, Lawrence R; Ferry, Judith A; Harris, Nancy Lee; Iafrate, A John; Bernstein, Bradley E; Sohani, Aliyah R; Le, Long Phi

2011-01-01

280

EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas  

PubMed Central

Mutations at codon 641 of EZH2 are recurrent in germinal center B cell lymphomas, and the most common variants lead to altered EZH2 enzymatic activity and enhanced tri-methylation of histone H3 at lysine 27, a repressive chromatin modification. As an initial step toward screening patients for cancer genotype-directed therapy, we developed a screening assay for EZH2 codon 641 mutations amenable for testing formalin-fixed clinical specimens, based on the sensitive SNaPshot single nucleotide extension technology. We detected EZH2 mutations in 12/55 (22%) follicular lymphomas (FL), 5/35 (14%) diffuse large B cell lymphomas with a germinal center immunophenotype (GCB-DLBCL), and 2/11 (18%) high grade B cell lymphomas with concurrent rearrangements of BCL2 and MYC. No EZH2 mutations were detected in cases of Burkitt lymphoma (0/23). EZH2 mutations were frequently associated with the presence of BCL2 rearrangement (BCL2-R) in both the FL (28% of BCL-R cases versus 0% of BCL2-WT cases, p<0.05) and GCB-DLBCL groups (33% of BCL2-R cases versus 4% of BCL2-WT cases, p<0.04), and across all lymphoma types excluding BL (27% of BCL2-R cases versus 3% of BCL2-WT cases, p<0.003). We confirmed gain-of-function activity for all previously reported EZH2 codon 641 mutation variants. Our findings suggest that EZH2 mutations constitute an additional genetic “hit” in many BCL2-rearranged germinal center B cell lymphomas. Our work may be helpful in the selection of lymphoma patients for future trials of pharmacologic agents targeting EZH2 and EZH2-regulated pathways. PMID:22194861

Ryan, Russell J. H.; Nitta, Mai; Borger, Darrell; Zukerberg, Lawrence R.; Ferry, Judith A.; Harris, Nancy Lee; Iafrate, A. John; Bernstein, Bradley E.

2011-01-01

281

The p53 Codon 72 Polymorphism Modifies the Cellular Response to Inflammatory Challenge in the Liver  

PubMed Central

The p53 protein is a critical stress-response mediator and signal coordinator in cellular metabolism and environmental exposure to deleterious agents. In human populations, the p53 gene contains a common single nucleotide polymorphism (SNP) affecting codon 72 that determines whether a proline (P72) or an arginine (R72) is present at this amino acid position of the polypeptide. Previous studies carried out using human populations, mouse models, and cell culture analyses have provided evidence that this amino acid difference can alter p53 functional activities, and potentially also can affect clinical presentation of disease. The clinical presentation associated with many forms of liver disease is variable, but few of the responsible underlying genetic factors or molecular pathways have been identified. The aim of the present study was to investigate whether the p53 codon 72 polymorphism influences the cellular response to hepatic stresses. A humanized p53 knock-in (Hupki) mouse model was used to address this issue. Mice expressing either the P72 or R72 normal variation of p53 were given an acute-, intermittent- or a chronic challenge, associated with exposure to lipopolysaccharide, D-galactosamine, or a high-fat diet. The results reveal that the livers of the P72 and R72 mice exhibit notable differences in inflammatory and apoptotic response to these distinct forms of stress. Interestingly the influence of this polymorphism on the response to stress is context dependent, with P72 showing increased response to liver toxins (lipopolysaccharide and D-galactosamine), but R72 showing increased response to metabolic stress (high fat diet). When taken together, these data point to the p53 codon 72 polymorphism as an important molecular mediator of events contributing to hepatic inflammation and metabolic homeostasis. PMID:23991369

Leu, Julia I-Ju; Murphy, Maureen E; George, Donna L

2013-01-01

282

Comparing internet and mobile phone usage: digital divides of usage, adoption, and dropouts  

Microsoft Academic Search

Results from a national representative telephone survey of Americans in 2000 show that Internet and mobile phone usage was very similar, and that several digital divides exist with respect to both Internet and mobile phone usage. The study identifies and analyzes three kinds of digital divides for both the Internet and mobile phones—users\\/nonuser, veteran\\/recent, and continuing\\/dropout—and similarities and differences among

Ronald E. Rice; James E. Katz

2003-01-01

283

Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals  

PubMed Central

Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated. PMID:25340584

Schink, Kay O.; Stehlik, Thorsten; Tillmann, Britta A. M.; Ast, Julia; Bolker, Michael

2014-01-01

284

Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals.  

PubMed

Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated. PMID:25340584

Stiebler, Alina C; Freitag, Johannes; Schink, Kay O; Stehlik, Thorsten; Tillmann, Britta A M; Ast, Julia; Bölker, Michael

2014-10-01

285

On the Importance of Oxidative Folding in the Evolution of Conotoxins: Cysteine Codon Preservation through Gene Duplication and Adaptation  

PubMed Central

Conotoxin genes are among the most rapidly evolving genes currently known; however, despite the well-established hypervariability of the intercysteine loops, the cysteines demonstrate significant conservation, with a site-specific codon bias for each cysteine in a family of conotoxins. Herein we present a novel rationale behind the codon-level conservation of the cysteines that comprise the disulfide scaffold. We analyze cysteine codon conservation using an internal reference and phylogenetic tools; our results suggest that the established codon conservation can be explained as the result of selective pressures linked to the production efficiency and folding of conotoxins, driving the conservation of cysteine at the amino-acid level. The preservation of cysteine has resulted in maintenance of the ancestral codon in most of the daughter lineages, despite the hypervariability of adjacent residues. We propose that the selective pressures acting on the venom components of cone snails involve an interplay of biosynthetic efficiency, activity at the target receptor and the importance of that activity to effective prey immobilization. Functional redundancy in the venom can thus serve as a buffer for the energy expenditure of venom production. PMID:24244311

Steiner, Andrew M.; Bulaj, Grzegorz; Puillandre, Nicolas

2013-01-01

286

Mutations in Caenorhabditis elegans eIF2? Permit Translation Initiation From Non-AUG Start Codons  

PubMed Central

Recognition of the AUG start codon on mRNAs during translation initiation in eukaryotes occurs in a preinitiation complex that includes small ribosomal subunits and multiple translation initiation factors. The complexity of this process and the lack of appropriate tools have prevented its genetic study in multicellular organisms. Here we describe a genetic system in the nematode Caenorhabditis elegans to study how the AUG start codon is selected. We have generated a sensitive reporter assay that allows for the isolation of mutants with reduced fidelity to recognize the AUG start codon. Two mutants were identified to have dominant missense mutations in iftb-1, which encodes the ?-subunit of eIF2 (eIF2?). Both mutations occur in a conserved region located outside of the C2–C2 zinc finger domain where yeast SUI3 mutations are localized in Saccharomyces cerevisiae eIF2?. C. elegans iftb-1, as well as mutant eIF2?s carrying the equivalent SUI3 mutations, are able to initiate translation at non-AUG codons that retain two potential base-pairing interactions with the anticodon of the initiator methionyl tRNA. These analyses further support the critical role of eIF2? in start codon selection, and two functional domains within eIF2? are likely involved, one defined by our C. elegans mutants and the other by the yeast SUI3 mutants. PMID:20215469

Zhang , Yinhua; Maduzia , Lisa L.

2010-01-01

287

Does the Clinical Phenotype of Fatal Familial Insomnia Depend on PRNP codon 129 Methionine-Valine Polymorphism?  

PubMed Central

Fatal familial insomnia (FFI) is a rare, hereditary prion-protein disease. Methionine-valine polymorphism at codon 129 of the prion-protein gene (PRNP) determines the phenotype in other hereditary prion-protein diseases, but association with the clinical phenotype in FFI remains uncertain. Early clinical findings in FFI comprise disturbances of the sleep-wake cycle and mild neuropsychiatric changes which typically emerge during middle to late adulthood. Here we describe an unusually early onset and rapid progression of FFI associated with dorsal midbrain involvement in a female patient with PRNP mutation at codon 178 and homozygote methionine polymorphism at codon 129. Early dorsal midbrain involvement became apparent by total loss of REM sleep and isolated bilateral trochlear nerve palsy. Early onset and rapid progression disease type associated with dorsal midbrain involvement may indicate a different spatiotemporal distribution of the neurodegenerative process in FFI patients with PRNP mutation and codon 129 methionine homozygosity compared to methioninevaline heterozygosity. Citation: Rupprecht S; Grimm A; Schultze T; Zinke J; Karvouniari P; Axer H; Witte OW; Schwab M. Does the clinical phenotype of fatal familial insomnia depend on PRNP codon 129 methionine-valine polymorphism? J Clin Sleep Med 2013;9(12):1343-1345. PMID:24340298

Rupprecht, Sven; Grimm, Alexander; Schultze, Torsten; Zinke, Jan; Karvouniari, Panagiota; Axer, Hubertus; Witte, Otto W.; Schwab, Matthias

2013-01-01

288

Experience with the use of the Codonics Safe Label System(™) to improve labelling compliance of anaesthesia drugs.  

PubMed

The Codonics Safe Labeling System(™) (http://www.codonics.com/Products/SLS/flash/) is a piece of equipment that is able to barcode scan medications, read aloud the medication and the concentration and print a label of the appropriate concentration in the appropriate colour code. We decided to test this system in our facility to identify risks, benefits and usability. Our project comprised a baseline survey (25 anaesthesia cases during which 212 syringes were prepared from 223 drugs), an observational study (47 cases with 330 syringes prepared) and a user acceptability survey. The baseline compliance with all labelling requirements was 58%. In the observational study the compliance using the Codonics system was 98.6% versus 63.8% with conventional labelling. In the user acceptability survey the majority agreed the Codonics machine was easy to use, more legible and adhered with better security than the conventional preprinted label. However, most were neutral when asked about the likelihood of flexibility and customisation and were dissatisfied with the increased workload. Our findings suggest that the Codonics labelling machine is user-friendly and it improved syringe labelling compliance in our study. However, staff need to be willing to follow proper labelling workflow rather than batch label during preparation. Future syringe labelling equipment developers need to concentrate on user interface issues to reduce human factor and workflow problems. Support logistics are also an important consideration prior to implementation of any new labelling system. PMID:24967766

Ang, S B L; Hing, W C; Tung, S Y; Park, T

2014-07-01

289

A Conformational Change in the Eukaryotic Translation Preinitiation Complex and Release of eIF1 Signal Recognition of the Start Codon  

Microsoft Academic Search

During eukaryotic translation initiation, ribosomal 43S complexes scan mRNAs for the correct AUG codon at which to begin translation. Start codon recognition triggers GTP hydrolysis, committing the complex to engagement at that point on the mRNA. While fidelity at this step is essential, the nature of the codon recognition event and the mechanism by which it activates GTP hydrolysis are

David Maag; Christie A. Fekete; Zygmunt Gryczynski; Jon R. Lorsch

2005-01-01

290

Characterization of codon-optimized recombinant candida rugosa lipase 5 (LIP5).  

PubMed

Recombinant Candida rugosa lipase 5 (LIP5) has been functionally expressed along with other isoforms in our laboratory. However, the characterization and codon optimization of LIP5 have not been done. In this work, we characterized, codon-optimized and compared LIP5 with commercial lipase. LIP5 activity on hydrolysis of p-nitrophenyl (p-NP) butyrate was optimal at 55 °C as compared with 37 °C of the commercial lipase. Several assays were also performed to determine the substrate specificity of LIP5. p-NP butyrate (C(4)), butyryl-CoA (C(4)), cholesteryl laurate (C(12)), and N-carbobenzoxy-l-tyrosine-p-nitrophenyl ester (l-NBTNPE) were found as preferred substrates of LIP5. Interestingly, LIP5 specificity on hydrolysis of amino acid-derivative substrates was shown to be the highest among any lipase isoforms, but it had very weak preference on hydrolyzing triacylglycerol substrates. LIP5 also displays a pH-dependent maximum activity of a lipase but an esterase substrate preference in general. The characterization of LIP5 along with that of LIP1-LIP4 previously identified shows that each lipase isoform has a distinct substrate preference and catalytic activity. PMID:21854055

Lee, Li-Chiun; Yen, Chih-Chung; Malmis, Conmar C; Chen, Long-Fang; Chen, Jen-Chieh; Lee, Guan-Chiun; Shaw, Jei-Fu

2011-10-12

291

Computational identification and sequence analysis of stop codon readthrough genes in Oryza sativa.  

PubMed

Using an approach based on the Readthrough Candidate Extraction System (RCES), we extracted 111 candidates from 9620 gene sequences of rice. The results of homology search and sequence analysis demonstrated that these candidates included actual readthrough genes that would be important for further investigating the mechanism of translation termination regulated by readthrough event, and could also give some useful clues for functional genome annotation. Between the candidates and non-candidates of gene sequences in rice, there exist significant base biases at the positions surrounding the stop codons. These positions, especially both -1 and +4, are referred to as part of an extended stop signal. In candidates, G at position -1, and G or C at position +4 are much more favored than that in non-candidates. Both stop sequence patterns, GUAGC and GUGAG, might drive high readthrough efficiency in rice. Secondary structure analysis revealed that the -1 and +1 amino acids around the first stop codon of candidates have a strong bias toward arginine, particularly the +1 position (20.7%), which indicated that the amino acids at the readthrough region being frequently located in the hydrophilic region of beta-turn might be a determinant for efficient translation termination or not. PMID:15527943

Liu, Qingpo; Xue, Qingzhong

2004-11-01

292

Codon optimisation improves the expression of Trichoderma viride sp. endochitinase in Pichia pastoris  

PubMed Central

The mature cDNA of endochitinase from Trichoderma viride sp. was optimised based on the codon bias of Pichia pastoris GS115 and synthesised by successive PCR; the sequence was then transformed into P. pastoris GS115 via electroporation. The transformant with the fastest growth rate on YPD plates containing 4?mg/mL G418 was screened and identified. This transformant produced 23.09?U/mL of the recombinant endochitinase, a 35% increase compared to the original strain bearing the wild-type endochitinase cDNA. The recombinant endochitinase was sequentially purified by ammonia sulphate precipitation, DE-52 anion-exchange chromatography and Sephadex G-100 size-exclusion chromatography. Thin-layer chromatography indicated that the purified endochitinase could hydrolyse chito-oligomers or colloidal chitin to generate diacetyl-chitobiose (GlcNAc)2 as the main product. This study demonstrates (1) a means for high expression of Trichoderma viride sp. endochitinase in P. pastoris using codon optimisation and (2) the preparation of chito-oligomers using endochitinase. PMID:24154717

Yu, Ping; Yan, Yuan; Gu, Qing; Wang, Xiangyang

2013-01-01

293

Kras gene codon 12 mutation detection enabled by gold nanoparticles conducted in a nanobioarray chip.  

PubMed

This study employs a nanobioarray (NBA) chip for multiple biodetection of single base pair mutations at the Kras gene codon 12. To distinguish between the mutant and wild-type target DNAs, current bioarray methods use high-temperature hybridization of the targets to the allele-specific probes. However, these techniques need prior temperature optimization and become harder to implement in the case of the detection of multiple mutations. We aimed to detect these mutations at a single temperature (room temperature), enabled by the use of gold nanoparticles (AuNPs) on the bioarray created within nanofluidic channels. In this method, a low amount of target oligonucleotides (5fmol) and polymerase chain reaction (PCR) products (300pg) were first loaded on the AuNP surface, and then these AuNP-bound targets were introduced into the channels of a polydimethylsiloxane (PDMS) glass chip. The targets hybridized to their complementary probes at the intersection of the target channels to the pre-printed oligonucleotide probe lines on the glass surface, creating a bioarray. Using this technique, fast and high-throughput multiple discrimination of the Kras gene codon 12 were achieved at room temperature using the NBA chip, and the specificity of the method was proved to be as high as that with the temperature stringency method. PMID:24291640

Sedighi, Abootaleb; Li, Paul C H

2014-03-01

294

Nucleotide modifications and tRNA anticodon-mRNA codon interactions on the ribosome  

PubMed Central

We have carried out molecular dynamics simulations of the tRNA anticodon and mRNA codon, inside the ribosome, to study the effect of the common tRNA modifications cmo5U34 and m6A37. In tRNAVal, these modifications allow all four nucleotides to be successfully read at the wobble position in a codon. Previous data suggest that entropic effects are mainly responsible for the extended reading capabilities, but detailed mechanisms have remained unknown. We have performed a wide range of simulations to elucidate the details of these mechanisms at the atomic level and quantify their effects: extensive free energy perturbation coupled with umbrella sampling, entropy calculations of tRNA (free and bound to the ribosome), and thorough structural analysis of the ribosomal decoding center. No prestructuring effect on the tRNA anticodon stem–loop from the two modifications could be observed, but we identified two mechanisms that may contribute to the expanded decoding capability by the modifications: The further reach of the cmo5U34 allows an alternative outer conformation to be formed for the noncognate base pairs, and the modification results in increased contacts between tRNA, mRNA, and the ribosome. PMID:22028366

Allner, Olof; Nilsson, Lennart

2011-01-01

295

Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster  

PubMed Central

Ribosomes can read through stop codons in a regulated manner, elongating rather than terminating the nascent peptide. Stop codon readthrough is essential to diverse viruses, and phylogenetically predicted to occur in a few hundred genes in Drosophila melanogaster, but the importance of regulated readthrough in eukaryotes remains largely unexplored. Here, we present a ribosome profiling assay (deep sequencing of ribosome-protected mRNA fragments) for Drosophila melanogaster, and provide the first genome-wide experimental analysis of readthrough. Readthrough is far more pervasive than expected: the vast majority of readthrough events evolved within D. melanogaster and were not predicted phylogenetically. The resulting C-terminal protein extensions show evidence of selection, contain functional subcellular localization signals, and their readthrough is regulated, arguing for their importance. We further demonstrate that readthrough occurs in yeast and humans. Readthrough thus provides general mechanisms both to regulate gene expression and function, and to add plasticity to the proteome during evolution. DOI: http://dx.doi.org/10.7554/eLife.01179.001 PMID:24302569

Dunn, Joshua G; Foo, Catherine K; Belletier, Nicolette G; Gavis, Elizabeth R; Weissman, Jonathan S

2013-01-01

296

Angelman syndrome due to a termination codon mutation of the UBE3A gene.  

PubMed

Angelman syndrome is a neurodevelopmental disorder characterized by global developmental delay, mental retardation, seizures, microcephaly, and severe speech delay. It may be caused by deletion of chromosome region 15q11.2 of the maternally inherited chromosome, mutations in the UBE3A gene, uniparental disomy, or imprinting defects. Most patients with this diagnosis have a severe phenotype, and a few have a mild form of the disease. We report a patient with a novel mutation in the UBE3A gene that consists of a deletion of the termination codon (c.2556-*+6del GTAAAACAAA) and results in an elongated protein E3 ubiquitin-protein ligase. Our patient has a mild phenotype compared with other patients in general and specifically to patients with UBE3A mutations. He has mild developmental delay, moderate speech delay, and no seizures. Recognition of this genotype-phenotype correlation will allow better genetic counseling to other patients with similar stop codon mutations. PMID:22566713

Al-Maawali, Almundher; Machado, Jerry; Fang, Ping; Dupuis, Lucie; Faghfoury, Hannaneh; Mendoza-Londono, Roberto

2013-03-01

297

Codon optimisation improves the expression of Trichoderma viride sp. endochitinase in Pichia pastoris.  

PubMed

The mature cDNA of endochitinase from Trichoderma viride sp. was optimised based on the codon bias of Pichia pastoris GS115 and synthesised by successive PCR; the sequence was then transformed into P. pastoris GS115 via electroporation. The transformant with the fastest growth rate on YPD plates containing 4?mg/mL G418 was screened and identified. This transformant produced 23.09?U/mL of the recombinant endochitinase, a 35% increase compared to the original strain bearing the wild-type endochitinase cDNA. The recombinant endochitinase was sequentially purified by ammonia sulphate precipitation, DE-52 anion-exchange chromatography and Sephadex G-100 size-exclusion chromatography. Thin-layer chromatography indicated that the purified endochitinase could hydrolyse chito-oligomers or colloidal chitin to generate diacetyl-chitobiose (GlcNAc)? as the main product. This study demonstrates (1) a means for high expression of Trichoderma viride sp. endochitinase in P. pastoris using codon optimisation and (2) the preparation of chito-oligomers using endochitinase. PMID:24154717

Yu, Ping; Yan, Yuan; Gu, Qing; Wang, Xiangyang

2013-01-01

298

Expression of codon optimized genes in microbial systems: current industrial applications and perspectives  

PubMed Central

The efficient production of functional proteins in heterologous hosts is one of the major bases of modern biotechnology. Unfortunately, many genes are difficult to express outside their original context. Due to their apparent “silent” nature, synonymous codon substitutions have long been thought to be trivial. In recent years, this dogma has been refuted by evidence that codon replacement can have a significant impact on gene expression levels and protein folding. In the past decade, considerable advances in the speed and cost of gene synthesis have facilitated the complete redesign of entire gene sequences, dramatically improving the likelihood of high protein expression. This technology significantly impacts the economic feasibility of microbial-based biotechnological processes by, for example, increasing the volumetric productivities of recombinant proteins or facilitating the redesign of novel biosynthetic routes for the production of metabolites. This review discusses the current applications of this technology, particularly those regarding the production of small molecules and industrially relevant recombinant enzymes. Suggestions for future research and potential uses are provided as well. PMID:24550894

Elena, Claudia; Ravasi, Pablo; Castelli, Maria E.; Peiru, Salvador; Menzella, Hugo G.

2014-01-01

299

Historical review of medicinal plants' usage  

PubMed Central

Healing with medicinal plants is as old as mankind itself. The connection between man and his search for drugs in nature dates from the far past, of which there is ample evidence from various sources: written documents, preserved monuments, and even original plant medicines. Awareness of medicinal plants usage is a result of the many years of struggles against illnesses due to which man learned to pursue drugs in barks, seeds, fruit bodies, and other parts of the plants. Contemporary science has acknowledged their active action, and it has included in modern pharmacotherapy a range of drugs of plant origin, known by ancient civilizations and used throughout the millennia. The knowledge of the development of ideas related to the usage of medicinal plants as well as the evolution of awareness has increased the ability of pharmacists and physicians to respond to the challenges that have emerged with the spreading of professional services in facilitation of man's life. PMID:22654398

Petrovska, Biljana Bauer

2012-01-01

300

Context-Aware Usage Control for Android  

Microsoft Academic Search

\\u000a The security of smart phones is increasingly important due to their rapid popularity. Mobile computing on smart phones introduces\\u000a many new characteristics such as personalization, mobility, pay-for-service and limited resources. These features require\\u000a additional privacy protection and resource usage constraints in addition to the security and privacy concerns on traditional\\u000a computers. As one of the leading open source mobile platform,

Guangdong Bai; Liang Gu; Tao Feng; Yao Guo; Xiangqun Chen

2010-01-01

301

Police -Usage de la force Fabien Jobard,  

E-print Network

Police - Usage de la force Fabien Jobard, CESDIP La police est l'une des institutions dépositaire du monopole de la violence physique légitime. Cette définition de la police, inspirée de celle de l sociologues de la police, principalement sous l'influence de l'ethnométhodologue Egon Bittner. Elle a été

Paris-Sud XI, Université de

302

Comparing Usage Performance on Mobile Applications  

Microsoft Academic Search

This paper presents an analysis tool for comparative and collaborative evaluation of mobile artefact usage. Three scenarios\\u000a were envisioned for the comparative dimension covering both multiple user performance analysis and single-user evolution analysis\\u000a through three different settings: result browsing, interaction replay and online monitoring. The collaborative dimension is\\u000a detailed according to two settings: existence of a public display and the

Luís Carriço; Luís Duarte; António Broega; Diogo Reis

2008-01-01

303

Reducing Energy Usage in Extractive Distillation  

E-print Network

, .. ~ REDUCING ENERGY USAGE IN,EXTRACTIVE DISTILLATION A. C. Saxena V. A. Bhandari Polysar Limited Sarnia, Ontario, Canada Abstract Butadiene 1:3 is separated from other C. hydrocarbons by extractive distillation in a sieve plate tower.... Prior to the development work to be described, the pressure in the extraction tower was controlled at a fixed value. The tower pressure-boilup control loop did not behave satisfactorily in the presence of non-condensables which entered with the feed...

Saxena, A. C.; Bhandari, V. A.

304

Cell phone usage and erectile function  

PubMed Central

Introduction The objective of this pilot study was to report our experience concerning the effects of cell phone usage on erectile function (EF) in men. Material and Methods We recruited 20 consecutive men complaining of erectile dysfunction (ED) for at least six months (Group A), and another group of 10 healthy men with no complaints of ED (Group B). Anamnesis, basic laboratory investigations, and clinical examinations were performed. All men completed the German version of the Sexual Health Inventory for Men (SHIM) for evaluation of the International Index of Erectile Function (IIEF), as well as another questionnaire designed by our clinicians that assessed cell phone usage habits. Results There was no significant difference between both groups regarding age, weight, height, and total testosterone (Table 1). The SHIM scores of Group A were significantly lower than that of Group B, 11.2 ±5 and 24.2 ±2.3, respectively. Total time spent talking on the cell phone per week was not significantly higher in Group A over B, 17.6 ±11.1 vs. 12.5 ±7 hours. Men with ED were found to carry their ‘switched on’ cell phones for a significantly longer time than those without ED, 4.4 ±3.6 vs. 1.8 ±1 hours per day. Conclusions We found a potential correlation with cell phone usage and a negative impact on EF. Further large–scale studies confirming our initial data and exploring the mechanisms involved in this phenomenon are recommended. PMID:24578997

Patzak, Johanna; Fischereder, Katja; Pummer, Karl; Shamloul, Rany

2013-01-01

305

Experimental reduction of codon bias in the Drosophila alcohol dehydrogenase gene results in decreased ethanol tolerance of adult flies.  

PubMed

The ethanol tolerance of adult transgenic flies of Drosophila containing between zero and ten unpreferred synonymous mutations that reduced codon bias in the alcohol dehydrogenase (Adh) gene was assayed. As the amino acid sequences of the ADH protein were identical in the four genotypes assayed, differences in ethanol tolerance were due to differences in the abundance of ADH protein, presumably driven by the effects of codon bias on translational efficiency. The ethanol tolerance of genotypes decreased with the number of unpreferred synonymous mutations, and a positive correlation between ADH protein abundance and ethanol tolerance was observed. This work confirms that the fitness effects of unpreferred synonymous mutations that reduce codon bias in a highly expressed gene are experimentally measurable in Drosophila melanogaster. PMID:15271077

Carlini, David B

2004-07-01

306

Low cytoplasmic mRNA levels of immunoglobulin kappa light chain genes containing nonsense codons correlate with inefficient splicing.  

PubMed Central

We have previously reported down-regulation of mRNA expression of some of the kappa light chain transgenes in a hybridoma derived from a secondary immune response. Of the five heavily mutated transgene copies present in that hybridoma, three included premature stop codons and were poorly represented at the mRNA level. Here we show that the nonsense mutations are the cause of the low mRNA levels. While we found no evidence that the reduction in mRNA abundance was attributable to an increased rate of cytoplasmic mRNA decay, the amount of cytoplasmic mRNA correlated with the accumulation of unspliced transcripts in the nucleus. Similar results were obtained with a chimeric immunoglobulin gene containing a premature chain termination codon in the variable gene segment. We suggest that inhibition of splicing induced by in-frame premature stop codons is an important mechanism for down-regulation of undesirable immunoglobulin transcripts. Images PMID:7925302

Lozano, F; Maertzdorf, B; Pannell, R; Milstein, C

1994-01-01

307

Making Sense of E-book Usage Data  

Microsoft Academic Search

This article provides an overview of the types of statistical data available for e-book usage and includes examples from specific vendors, along with coverage of standards such as COUNTER (Counting Online Usage of Networked Electronic Resources). It describes ways in which usage data can be employed for purposes such as monitoring of e-book uptake and collection development. Limitations with regard

John Cox

2008-01-01

308

Training Evaluation Overfitting Optimising Data Usage Summary Training and Testing  

E-print Network

Training Evaluation Overfitting Optimising Data Usage Summary Lecture 2 Training and Testing University of Amsterdam #12;Training Evaluation Overfitting Optimising Data Usage Summary 1 Training k-validation 5 Summary #12;Training Evaluation Overfitting Optimising Data Usage Summary 1 Training k

Englebienne, Gwenn

309

Random codon re-encoding induces stable reduction of replicative fitness of Chikungunya virus in primate and mosquito cells.  

PubMed

Large-scale codon re-encoding represents a powerful method of attenuating viruses to generate safe and cost-effective vaccines. In contrast to specific approaches of codon re-encoding which modify genome-scale properties, we evaluated the effects of random codon re-encoding on the re-emerging human pathogen Chikungunya virus (CHIKV), and assessed the stability of the resultant viruses during serial in cellulo passage. Using different combinations of three 1.4 kb randomly re-encoded regions located throughout the CHIKV genome six codon re-encoded viruses were obtained. Introducing a large number of slightly deleterious synonymous mutations reduced the replicative fitness of CHIKV in both primate and arthropod cells, demonstrating the impact of synonymous mutations on fitness. Decrease of replicative fitness correlated with the extent of re-encoding, an observation that may assist in the modulation of viral attenuation. The wild-type and two re-encoded viruses were passaged 50 times either in primate or insect cells, or in each cell line alternately. These viruses were analyzed using detailed fitness assays, complete genome sequences and the analysis of intra-population genetic diversity. The response to codon re-encoding and adaptation to culture conditions occurred simultaneously, resulting in significant replicative fitness increases for both re-encoded and wild type viruses. Importantly, however, the most re-encoded virus failed to recover its replicative fitness. Evolution of these viruses in response to codon re-encoding was largely characterized by the emergence of both synonymous and non-synonymous mutations, sometimes located in genomic regions other than those involving re-encoding, and multiple convergent and compensatory mutations. However, there was a striking absence of codon reversion (<0.4%). Finally, multiple mutations were rapidly fixed in primate cells, whereas mosquito cells acted as a brake on evolution. In conclusion, random codon re-encoding provides important information on the evolution and genetic stability of CHIKV viruses and could be exploited to develop a safe, live attenuated CHIKV vaccine. PMID:23436995

Nougairede, Antoine; De Fabritus, Lauriane; Aubry, Fabien; Gould, Ernest A; Holmes, Edward C; de Lamballerie, Xavier

2013-02-01

310

ANALYSIS OF K-RAS GENE CODON 12 MUTATION IN PANCREATIC TISSUE OF PATIENTS WITH PANCREATIC CANCER  

E-print Network

Abstract — The aim of this study was to analyze K-ras codon 12 mutation in the pancreatic tissue of Serbian patients with pancreatic cancer and assess whether the given mutation can be used as a molecular marker for this disease. The study was performed on pancreatic tissue samples obtained from 40 patients with clinical diagnosis of pancreatic cancer. The presence of K-ras codon 12 mutation was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our study showed that K-ras mutation is present with a high frequency (66%) in the pancreatic tissue of patients with pancretic cancer.

Aleksandra Nikoli?; S. Kneževi?; Mila Krsmanovi?; M. Micev; M. Ristanovi?; Dragica Radojkovi?

311

Usage-Based versus Measure-Based Unit Pricing: Is there a Better Index of Value?  

Microsoft Academic Search

In many product categories, unit prices facilitate price comparisons across brands and package sizes; this enables consumers\\u000a to identify those products that provide the greatest value. However in other product categories, unit prices may be confusing.\\u000a This is because there are two types of unit pricing, measure-based and usage-based. Measure-based unit prices are what the\\u000a name implies; price is expressed

Robert J. Kwortnik Jr; Elizabeth H. Creyer; William T. Ross Jr

2006-01-01

312

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

SciTech Connect

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

Feng, Yue; Gunter, L.E.; Organ, E.L.; Cavener, D.R. (Vanderbilt University, Nashville, TN (United States))

1991-04-01

313

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

PubMed

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. PMID:25070322

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

2014-01-01

314

Why Time Matters: Codon Evolution and the Temporal Dynamics of dN/dS  

PubMed Central

The ratio of divergence at nonsynonymous and synonymous sites, dN/dS, is a widely used measure in evolutionary genetic studies to investigate the extent to which selection modulates gene sequence evolution. Originally tailored to codon sequences of distantly related lineages, dN/dS represents the ratio of fixed nonsynonymous to synonymous differences. The impact of ancestral and lineage-specific polymorphisms on dN/dS, which we here show to be substantial for closely related lineages, is generally neglected in estimation techniques of dN/dS. To address this issue, we formulate a codon model that is firmly anchored in population genetic theory, derive analytical expressions for the dN/dS measure by Poisson random field approximation in a Markovian framework and validate the derivations by simulations. In good agreement, simulations and analytical derivations demonstrate that dN/dS is biased by polymorphisms at short time scales and that it can take substantial time for the expected value to settle at its time limit where only fixed differences are considered. We further show that in any attempt to estimate the dN/dS ratio from empirical data the effect of the intrinsic fluctuations of a ratio of stochastic variables, can even under neutrality yield extreme values of dN/dS at short time scales or in regions of low mutation rate. Taken together, our results have significant implications for the interpretation of dN/dS estimates, the McDonald–Kreitman test and other related statistics, in particular for closely related lineages. PMID:24129904

Mugal, Carina F.; Wolf, Jochen B.W.; Kaj, Ingemar

2014-01-01

315

An assessment of worldwide supercomputer usage  

SciTech Connect

This report provides a comparative study of advanced supercomputing usage in Japan and the United States as of Spring 1994. It is based on the findings of a group of US scientists whose careers have centered on programming, evaluating, and designing high-performance supercomputers for over ten years. The report is a follow-on to an assessment of supercomputing technology in Europe and Japan that was published in 1993. Whereas the previous study focused on supercomputer manufacturing capabilities, the primary focus of the current work was to compare where and how supercomputers are used. Research for this report was conducted through both literature studies and field research in Japan.

Wasserman, H.J.; Simmons, M.L.; Hayes, A.H.

1995-01-01

316

Clinical significance of HIV-1 coreceptor usage  

PubMed Central

The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage. PMID:21284904

2011-01-01

317

Contrast in Usage of FCAT-Approved Anatomical Terminology Between Members of Two Anatomy Associations in North America  

NSDL National Science Digital Library

This article describes the outcomes of a AAA survey comparing the frequency of FCAT term usage among HAPS instructors. The survey had already been conducted among AAA members and comparisons between societies were made. An initial reporting of the differences and similarities among societies and anatomy teaching backgrounds are discussed.

Bradford Martin (Loma Linda University Physical Therapy)

2009-11-04

318

The AUG start codon of the Saccharomyces cerevisiae NFS1 gene can be substituted for by UUG without increased initiation of translation at  

E-print Network

increased initiation of translation at downstream codons Ju¨ rgen H. Nett, Jacques Kessl, Tina Wenz of the site for initiation of translation for the Saccharomyces cerevisiae NFS1 gene was examined using mRNA was translated in vitro using a reticulocyte system, initiation from the mutated codon

Trumpower, Bernard L.

319

Life without tRNA[superscript Ile]-lysidine synthetase: translation of the isoleucine codon AUA in Bacillus subtilis lacking the canonical tRNA[Ile over 2  

E-print Network

Translation of the isoleucine codon AUA in most prokaryotes requires a modified C (lysidine or agmatidine) at the wobble position of tRNA[Ile over 2] to base pair specifically with the A of the AUA codon but not with the ...

Koehrer, Caroline

320

Guanidine reduces stop codon read-through caused by missense mutations inSUP35 orSUP45  

Microsoft Academic Search

Sup35 and Sup45 are essential protein components of the Saccharomyces cerevisiae translation termination factor. Yeast cells harbouring the (PSI +) prion form of Sup35 have impaired stop codon recognition (nonsense suppression). It has long been known that the (PSI +) prion is not stably transmitted to daughter cells when yeast are grown in the presence of mM concentrations of guanidine

Michael E. Bradley; Sviatoslav Bagriantsev; Namitha Vishveshwara; Susan W. Liebman

2003-01-01

321

Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie.  

PubMed

Scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep. It belongs to the group of prion diseases also affecting man in which an abnormal isoform of the host-encoded prion protein (PrP) accumulating in the brain is responsible for neuronal death. Three main polymorphisms have been described in the sheep PrP gene, at positions 136, 154 and 171. A strong association between susceptibility/resistance to natural scrapie and a dimorphism at codon 136 of the ovine PrP gene has been reported in several breeds, including Romanov. This dimorphism, however, is not found in all scrapie-affected breeds. We have compared the PrP genotypes of Lacaune sheep obtained from enzootically affected flocks with those of apparently healthy sheep. A third variant at codon 171 was also evidenced. The results were compared with those obtained in a single experimental Romanov flock orally challenged with nematode parasites in which scrapie suddenly appeared and killed 80% of the sheep. We present evidence that, even in different epizootological circumstances, the major genetic factor controlling the susceptibility/resistance to natural scrapie in sheep, is represented by codon 171 genotype of the PrP gene. We also suggest that a modification of the allelic effects of codon 136 can occur in heavily infected animals. PMID:7636494

Clouscard, C; Beaudry, P; Elsen, J M; Milan, D; Dussaucy, M; Bounneau, C; Schelcher, F; Chatelain, J; Launay, J M; Laplanche, J L

1995-08-01

322

The other codons: Nirenberg and the genetic code, 2D animationSite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

After the easy codons, exact triplets had to be made in order to finish deciphering the rest. Marshall Nirenberg and a group of scientists including Maxine Singer, Marianne Grunberg-Manago, Phil Leder were involved in this process. Har Gobind Khorana also worked on this problem.

2008-10-06

323

The Roles of Serum Leptin Concentration and Polymorphism in Leptin Receptor Gene at Codon 109 in Breast Cancer  

Microsoft Academic Search

Aims: We investigated the relationship between serum leptin concentrations and polymorphism of the leptin receptor gene and breast cancer. Methods: Serum leptin concentrations were measured by enzyme-linked immunosorbent assay in 47 women with invasive breast cancer compared with 41 age-matched controls without cancer. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the leptin receptor gene at codon 109

Chien-Liang Liu; Yuan-Ching Chang; Shih-Ping Cheng; Schu-Rern Chern; Tsen-Long Yang; Jie-Jen Lee; Ing-Cherng Guo; Chih-Ping Chen

2007-01-01

324

A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease  

Microsoft Academic Search

Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflam- matory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the

Thomas R. Hawn; Annelies Verbon; Kamilla D. Lettinga; Lue Ping Zhao; Shuying Sue Li; Richard J. Laws; Shawn J. Skerrett; Bruce Beutler; Lea Schroeder; Alex Nachman; Adrian Ozinsky; Kelly D. Smith; Alan Aderem

2003-01-01

325

Usage analysis of user files in UNIX  

NASA Technical Reports Server (NTRS)

Presented is a user-oriented analysis of short term file usage in a 4.2 BSD UNIX environment. The key aspect of this analysis is a characterization of users and files, which is a departure from the traditional approach of analyzing file references. Two characterization measures are employed: accesses-per-byte (combining fraction of a file referenced and number of references) and file size. This new approach is shown to distinguish differences in files as well as users, which cam be used in efficient file system design, and in creating realistic test workloads for simulations. A multi-stage gamma distribution is shown to closely model the file usage measures. Even though overall file sharing is small, some files belonging to a bulletin board system are accessed by many users, simultaneously and otherwise. Over 50% of users referenced files owned by other users, and over 80% of all files were involved in such references. Based on the differences in files and users, suggestions to improve the system performance were also made.

Devarakonda, Murthy V.; Iyer, Ravishankar K.

1987-01-01

326

Maternal Control Strategies, Maternal Language Usage and Children's Language Usage at Two Years  

ERIC Educational Resources Information Center

The present study determined whether parenting style, defined by control strategies varying in power-assertion mediated the established relation between maternal language usage (grammar and semantics) and child language (grammar, semantics and pragmatics) during toddlerhood (n = 60). Based upon their use of control strategies mothers were…

Taylor, Nicole; Donovan, Wilberta; Miles, Sally; Leavitt, Lewis

2009-01-01

327

1 Resource Usage and User Preferences in Benefit Functions An Approach to Characterizing Resource Usage  

E-print Network

for the duration of the job. As there are multiple users accessing the same resources, there are naturally various1 Resource Usage and User Preferences in Benefit Functions An Approach to Characterizing Resource of resources consumed by jobs under the control of a Resource Management System, and it is shown how

328

High-level tetracycline resistance mediated by efflux pumps Tet(A) and Tet(A)-1 with two start codons.  

PubMed

Efflux is the most common mechanism of tetracycline resistance. Class A tetracycline efflux pumps, which often have high prevalence in Enterobacteriaceae, are encoded by tet(A) and tet(A)-1 genes. These genes have two potential start codons, GTG and ATG, located upstream of the genes. The purpose of this study was to determine the start codon(s) of the class A tetracycline resistance (tet) determinants tet(A) and tet(A)-1, and the tetracycline resistance level they mediated. Conjugation, transformation and cloning experiments were performed and the genetic environment of tet(A)-1 was analysed. The start codons in class A tet determinants were investigated by site-directed mutagenesis of ATG and GTG, the putative translation initiation codons. High-level tetracycline resistance was transferred from the clinical strain of Klebsiella pneumoniae 10-148 containing tet(A)-1 plasmid pHS27 to Escherichia coli J53 by conjugation. The transformants harbouring recombinant plasmids that carried tet(A) or tet(A)-1 exhibited tetracycline MICs of 256-512 µg ml(-1), with or without tetR(A). Once the ATG was mutated to a non-start codon, the tetracycline MICs were not changed, while the tetracycline MICs decreased from 512 to 64 µg ml(-1) following GTG mutation, and to ?4 µg ml(-1) following mutation of both GTG and ATG. It was presumed that class A tet determinants had two start codons, which are the primary start codon GTG and secondary start codon ATG. Accordingly, two putative promoters were predicted. In conclusion, class A tet determinants can confer high-level tetracycline resistance and have two start codons. PMID:25102906

Wang, Weixia; Guo, Qinglan; Xu, Xiaogang; Sheng, Zi-Ke; Ye, Xinyu; Wang, Minggui

2014-11-01

329

Technology Empowerment as a Determinant of Salesforce Technology Usage  

Microsoft Academic Search

Abstract The purpose,of,this research,was to investigate how salespeople technology empowerment,impacts,their usage of technology. Although empowerment,has been investigated in the area of sales, no research has yet investigated technology empowerment,and its impact on salespeople technology usage. The relationship between technology empowerment, a multidimensional construct composed of four underlying dimensions (competence, autonomy, motivation, and impact) and technology usage was tested using a

Amy Chou

330

Cleaning optimization for reduced chemical usage  

SciTech Connect

The use of dilute SC-1 (NH40H:H202:H20) chemistry cleaning processes for particle removal from silicon surfaces has been investigated. Dilute chemistries can be highly effective, especially when high- frequency acoustic energy (megasonics) is applied. The high particle removal efficacy of the dilute chemistry processes presumably arises due to increased double layer effects caused by reduced ionic strength. Dilute chemistry SC- I solutions exhibit somewhat reduced efficacy for removal of certain light organics; however, when dilute SC-1 is used along with other pre-gate cleaning steps (e.g. HF, SC-2, and piranha), then the overall cleaning sequence is quite effective. In addition to providing robust cleaning processes, dilute chemistries also result in significantly lower chemical and rinse water usage. Waste water treatment requirements are also lessened when dilute chemistry cleaning solutions are employed.

Resnick, P.J.; Simonson, G.C.; Matlock, C.A.; Kelly, M.J.

1996-11-01

331

Water and energy usage in synfuel production  

SciTech Connect

The water and energy requirements for converting coal, oil shale and biomass to synthetic liquid and gaseous fuels have been analyzed. Based on overall material and energy balance, an evaluation of the net energy consumption, conversion efficiency, process and cooling water requirements have been performed for coal gasification, coal liquefaction, oil shale processing (both surface and modified in-situ retorting) and biomass to ethanol conversion. Theoretical bases are developed to determine the limits for the rates of process and cooling water consumption. The water usage is analyzed in terms of conversion efficiency and process alternatives. Among the five synfuel processes studied, the biomass to ethanol conversion is found to be least energy efficient and most water intensive while the coal liquefaction is least water intensive.

Chiang, S.H.; James, I.C.

1980-12-01

332

Cloning and in vitro function analysis of codon-optimized FatI gene.  

PubMed

Currently, n-3 polyunsaturated fatty acids (n-3 PUFAs) have attracted great attention because of their biological significance to organisms. In addition, PUFAs show an obvious impact on prevention and treatment of various diseases. Because n-3 PUFAs cannot be endogenously synthesized by mammals, mammals have to rely on a dietary supplement for sufficient supply. The finding and application of the fatty acid dehydrogenase I (FatI) gene are expected to change the current situation because it can convert n-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. Meanwhile, the gradual maturation of transgenic technology makes it possible to produce transgenic animals that can synthesize n-3 PUFAs by themselves. In this study, the DNA coding sequence of FatI was synthesized by a chemical method after codon optimization according to the mammal's codon bias. The synthesized DNA sequence was introduced into Boer goat fetal fibroblasts by the constructed recombinant eukaryotic expression vector pcDNA3.1(+)-FatI. Boer goat fetal fibroblasts were transfected by electroporation, and the stable transfected cell lines were obtained by G418 selection. Genomic DNA PCR and Southern blot were applied to verify that the foreign gene FatI was integrated into the genome of the Boer goat fibroblasts. RT-PCR results showed the expression of FatI gene at the mRNA level. The fatty acid profile of cells carrying the FatI gene revealed an increase in total n-3 PUFAs (from 0.61 to 0.95), but a decrease in n-6 PUFAs (from 10.34 to 9.85), resulting in a remarkable increase in the n-3:n-6 ratio (from 0.059 to 0.096). The n-3:n-6 ratio had a 63.49 percent increase, which is a precursor of the response of n-3 desaturase activity of the FatI gene. The study may provide a practical tool for producing transgenic animals that can produce n-3 PUFAs by themselves, and we hope that the application will lay the foundation for animals producing n-3 PUFAs, which will benefit human nutrition and wellness. PMID:24117953

Sun, Xiao-Feng; Sun, Xing-Hong; Teng, Mei-Li; Liu, Huan-Qi; Min, Ling-Jiang; Pan, Qing-Jie; Qin, Guo-Qing; Shen, Wei; Li, Lan

2014-01-01

333

File Usage Analysis and Resource Usage Prediction: a Measurement-Based Study. Ph.D. Thesis  

NASA Technical Reports Server (NTRS)

A probabilistic scheme was developed to predict process resource usage in UNIX. Given the identity of the program being run, the scheme predicts CPU time, file I/O, and memory requirements of a process at the beginning of its life. The scheme uses a state-transition model of the program's resource usage in its past executions for prediction. The states of the model are the resource regions obtained from an off-line cluster analysis of processes run on the system. The proposed method is shown to work on data collected from a VAX 11/780 running 4.3 BSD UNIX. The results show that the predicted values correlate well with the actual. The coefficient of correlation between the predicted and actual values of CPU time is 0.84. Errors in prediction are mostly small. Some 82% of errors in CPU time prediction are less than 0.5 standard deviations of process CPU time.

Devarakonda, Murthy V.-S.

1987-01-01

334

Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria.  

PubMed

Vertebrate mitochondria use stop codons UAA and UAG decoded by the release factor (RF) MTRF1L and two reassigned arginine codons, AGA and AGG. A second highly conserved RF-like factor, MTRF1, which evolved from a gene duplication of an ancestral mitochondrial RF1 and not a RF2, is a good candidate for recognizing the nonstandard codons. MTRF1 differs from other RFs by having insertions in the two external loops important for stop codon recognition (tip of helix alpha5 and recognition loop) and by having key substitutions that are involved in stop codon interactions in eubacterial RF/ribosome structures. These changes may allow recognition of the larger purine base in the first position of AGA/G and, uniquely for RFs, only of G at position 2. In contrast, residues that support A and G recognition in the third position in RF1 are conserved as would be required for recognition of AGA and AGG. Since an assay with vertebrate mitochondrial ribosomes has not been established, we modified Escherichia coli RF1 at the helix alpha5 and recognition loop regions to mimic MTRF1. There was loss of peptidyl-tRNA hydrolysis activity with standard stop codons beginning with U (e.g., UAG), but a gain of activity with codons beginning with A (AAG in particular). A lower level of activity with AGA could be enhanced by solvent modification. These observations imply that MTRF1 has the characteristics to recognize A as the first base of a stop codon as would be required to decode the nonstandard codons AGA and AGG. PMID:20421313

Young, David J; Edgar, Christina D; Murphy, Jennifer; Fredebohm, Johannes; Poole, Elizabeth S; Tate, Warren P

2010-06-01

335

Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and Near Stop Codons  

PubMed Central

SUMMARY Methylation of the N6 position of adenosine (m6A) is a post-transcriptional modification of RNA whose prevalence and physiological relevance is poorly understood. The recent discovery that FTO, an obesity risk gene, encodes an m6A demethylase implicates m6A as an important regulator of physiological processes. Here we present a method for transcriptome-wide m6A localization, which combines m6A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676 mammalian genes that contain m6A, indicating that m6A is a common base modification of mRNA. The m6A modification exhibits tissue-specific regulation and is markedly increased throughout brain development. We find that m6A sites are enriched near stop codons and in 3' UTRs, and we uncover an association between m6A residues and microRNA binding sites within 3' UTRs. These findings provide a resource for identifying transcripts that are substrates for adenosine methylation and reveal insights into the epigenetic regulation of the mammalian transcriptome. PMID:22608085

Meyer, Kate D.; Saletore, Yogesh; Zumbo, Paul; Elemento, Olivier; Mason, Christopher E.; Jaffrey, Samie R.

2012-01-01

336

Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons.  

PubMed

Methylation of the N(6) position of adenosine (m(6)A) is a posttranscriptional modification of RNA with poorly understood prevalence and physiological relevance. The recent discovery that FTO, an obesity risk gene, encodes an m(6)A demethylase implicates m(6)A as an important regulator of physiological processes. Here, we present a method for transcriptome-wide m(6)A localization, which combines m(6)A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq). We use this method to identify mRNAs of 7,676 mammalian genes that contain m(6)A, indicating that m(6)A is a common base modification of mRNA. The m(6)A modification exhibits tissue-specific regulation and is markedly increased throughout brain development. We find that m(6)A sites are enriched near stop codons and in 3' UTRs, and we uncover an association between m(6)A residues and microRNA-binding sites within 3' UTRs. These findings provide a resource for identifying transcripts that are substrates for adenosine methylation and reveal insights into the epigenetic regulation of the mammalian transcriptome. PMID:22608085

Meyer, Kate D; Saletore, Yogesh; Zumbo, Paul; Elemento, Olivier; Mason, Christopher E; Jaffrey, Samie R

2012-06-22

337

Structural Evidence for a Germline-Encoded T Cell Receptor - Major Histocompatibility Complex Interaction 'Codon'  

SciTech Connect

All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable {beta}-chain 8.2 (V{sub {beta}}8.2), each bound to the MHC class II molecule I-A{sup u}, and did energetic mapping of V{sub {alpha}} and V{sub {beta}} contacts with I-A{sup u}. Together with two previously solved structures of V{sub {beta}}8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V{sub {beta}} loops and the I-A {alpha}-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.

Feng, D.; Bond, C.J.; Ely, L.K.; Maynard, J.; Garcia, K.C.

2009-06-02

338

Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase.  

PubMed

We identified a deletion at codon 70 (Delta70) of HIV-1 reverse transcriptase (RT) occurring together with L74V and Q151M mutations in a sample from a tenofovir (TFV)- and abacavir (ABC)-treated patient with extensive prior antiretroviral treatment. To investigate the characteristics of this mutant, we studied the drug susceptibility, relative infectivity, and fitness of viruses carrying Delta70 and associated RT mutations. The Delta70, L74V, and Q151M mutations were introduced into Hxb2 RT by site-directed mutagenesis and expressed in HIV-1 recombinants. The Delta70 mutation increased resistance to lamivudine and emtricitabine alone and in combination with various resistance mutations and augmented resistance to ABC and didanosine when present together with L74V. A recombinant virus expressing RT from the original clinical viral sample (Delta70-PRT) exhibited greater fitness than one in which the deletion had been repaired (K70-PRT). The Delta70 mutation also increased fitness of Hxb2 wild-type and 74V and Q151M mutants. Recombinants carrying Delta70-PRT showed greater relative infectivity in the presence of ABC (but not TFV) compared with K70-PRT recombinants. These results show that Delta70 enhances resistance to certain purine and pyrimidine analogues and contributes to multinucleoside resistance in the appropriate viral genetic background. PMID:17496561

Hu, Zixin; Hatano, Hiroyu; Hammond, Sarah P; Smith, Danielle; Wild, Mary; Gupta, Soumi; Whitcomb, Jeannette; Kalayjian, Robert C; Gripshover, Barbara; Kuritzkes, Daniel R

2007-08-15

339

Stimulation of stop codon readthrough: frequent presence of an extended 3? RNA structural element  

PubMed Central

In Sindbis, Venezuelan equine encephalitis and related alphaviruses, the polymerase is translated as a fusion with other non-structural proteins via readthrough of a UGA stop codon. Surprisingly, earlier work reported that the signal for efficient readthrough comprises a single cytidine residue 3?-adjacent to the UGA. However, analysis of variability at synonymous sites revealed strikingly enhanced conservation within the ?150?nt 3?-adjacent to the UGA, and RNA folding algorithms revealed the potential for a phylogenetically conserved stem–loop structure in the same region. Mutational analysis of the predicted structure demonstrated that the stem–loop increases readthrough by up to 10-fold. The same computational analysis indicated that similar RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furovirus, Pomovirus, Tobravirus, Pecluvirus and Benyvirus, as well as the Drosophilia gene kelch. These results suggest that 3? RNA stimulatory structures feature in a much larger proportion of readthrough cases than previously anticipated, and provide a new criterion for assessing the large number of cellular readthrough candidates that are currently being revealed by comparative sequence analysis. PMID:21525127

Firth, Andrew E.; Wills, Norma M.; Gesteland, Raymond F.; Atkins, John F.

2011-01-01

340

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

PubMed Central

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

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

2011-01-01

341

Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote.  

PubMed

Aminoacyl-tRNA synthetase (aaRS) catalyzes the first step of protein synthesis, producing aminoacyl-tRNAs as building blocks. Eukaryotic aaRS differs from its prokaryotic counterpart in terminal extension or insertion. Moreover, the editing function of aaRSs is an indispensable checkpoint excluding non-cognate amino acids at a given codon and ensuring overall translational fidelity. We found higher eukaryotes encode two cytoplasmic threonyl-tRNA synthetases (ThrRSs) with difference in N-terminus. The longer isoform is more closely related to the ThrRSs of higher eukaryotes than to those of lower eukaryotes. A yeast strain was generated to include deletion of the thrS gene encoding ThrRS. Combining in vitro biochemical and in vivo genetic data, ThrRSs from eukaryotic cytoplasm were systematically analyzed, and role of the eukaryotic cytoplasmic ThrRS-specific N-terminal extension was elucidated. Furthermore, the mechanisms of aminoacylation and editing activity mediated by Saccharomyces cerevisiae ThrRS (ScThrRS) were clarified. Interestingly, yeast cells were tolerant of variation at the editing active sites of ScThrRS without significant Thr-to-Ser conversion in the proteome even under significant environmental stress, implying checkpoints downstream of aminoacylation to provide a further quality control mechanism for the yeast translation system. This study has provided the first comprehensive elucidation of the translational fidelity control mechanism of eukaryotic ThrRS. PMID:23093606

Zhou, Xiao-Long; Ruan, Zhi-Rong; Huang, Qian; Tan, Min; Wang, En-Duo

2013-01-01

342

Dynamics of a genetic toggle switch at the nucleotide and codon levels  

NASA Astrophysics Data System (ADS)

We study the dynamics of a model stochastic two-gene switch at the nucleotide and codon levels. First, we show that its stability, the mean lifetime of the noisy attractors, differs from that of a model where transcription and translation elongation are modeled as single-step delayed events, indicating the need of detailed models to study the dynamics of switches. Next, we vary the coupling between the two genes by varying the affinity of repressor proteins to the promoters and measure the mutual information between the two proteins times series. We find that there is a degree of coupling that maximizes information propagation between the two genes. This is explained by the effects of the coupling on mean and entropy of RNA and protein numbers of each gene, as well as correlation, 2-tuple entropy between the two proteins numbers, and, finally, the stability of the noisy attractors. We also find that increasing the rate of translation initiation increases the correlation between RNA and protein numbers and between the two proteins, due to increased stability of the noisy attractors. Increasing the rate of transcription or decreasing RNA degradation causes opposite effects to the correlation between RNA and proteins of each gene and the stability of the noisy attractors. Finally, we add a sequence-dependent transcription pause site and show that both its probability of occurrence, as well as its mean time length, affects the dynamics of the switch, further demonstrating the dependence of the dynamics of this circuit on sequence level events.

Potapov, Ilya; Lloyd-Price, Jason; Yli-Harja, Olli; Ribeiro, Andre S.

2011-09-01

343

Enhanced purification and characterization of the PfeIF4A (PfH45) helicase from Plasmodium falciparum using a codon-optimised clone.  

PubMed

With the intention of investigating the DNA strand displacement properties of Plasmodium falciparum helicase PfeIF4A (formerly known as PfH45) a codon-optimized gene for expression in Escherichia coli has been produced. Several histidine-containing proteins with intrinsic helicase activity were captured from the bacterial sonicate by initial Ni(2+)-chromatography. Heparin and size-exclusion steps were subsequently required for unambiguous PfeIF4A purification. This strategy generated an active recombinant protein of significantly improved yield in comparison to previously published studies (~4.2 mg/g wet weight of cells). Helicase unwinding assays confirmed a bipolar activity, but revealed a preference for unwinding a free 3'-end, with a rate of displacement in the 3'-5' direction 2-fold higher than that in the 5'-3' direction. DNA constructs with two, three or four blunt ends were not unwound. Studies confirmed the enzyme to be Mg(2+)-dependent, optimally active at 37°C and had a background ATP turnover rate of 23.16±1.74 pmol/min, which in the presence of single- or double-stranded DNA doubled to 42.92±3.21 pmol/min. PMID:22750398

Evans, Luke; Gowers, Darren; Firman, Keith; Youell, James

2012-09-01

344

Hemoglobin E and codon 17 nonsense: two beta-globin gene mutations common in Southeast Asia detected by the use of ARMS.  

PubMed

Hemoglobin E (codon 26 GAG-->AAG) and codon 17 nonsense (AAG-->TAG), two clinically important mutations of the beta-globin gene, are common in Southeast Asia. The detection of these mutations using allele-specific PCR is described. Together with the previously reported method for the detection of the common Southeast asian codon 41-42 frameshift mutation (del CTTT), it is possible to identify the vast majority of clinically important beta-globin gene mutations in Southeast Asian populations by means of nonradioactive methods. PMID:8373896

Steger, H; Eigel, A; Flatz, G; Horst, J

1993-09-01

345

Web-based pathology practice examination usage  

PubMed Central

Context: General and subject specific practice examinations for students in health sciences studying pathology were placed onto a free public internet web site entitled web path and were accessed four clicks from the home web site menu. Subjects and Methods: Multiple choice questions were coded into. html files with JavaScript functions for web browser viewing in a timed format. A Perl programming language script with common gateway interface for web page forms scored examinations and placed results into a log file on an internet computer server. The four general review examinations of 30 questions each could be completed in up to 30 min. The 17 subject specific examinations of 10 questions each with accompanying images could be completed in up to 15 min each. The results of scores and user educational field of study from log files were compiled from June 2006 to January 2014. Results: The four general review examinations had 31,639 accesses with completion of all questions, for a completion rate of 54% and average score of 75%. A score of 100% was achieved by 7% of users, ?90% by 21%, and ?50% score by 95% of users. In top to bottom web page menu order, review examination usage was 44%, 24%, 17%, and 15% of all accessions. The 17 subject specific examinations had 103,028 completions, with completion rate 73% and average score 74%. Scoring at 100% was 20% overall, ?90% by 37%, and ?50% score by 90% of users. The first three menu items on the web page accounted for 12.6%, 10.0%, and 8.2% of all completions, and the bottom three accounted for no more than 2.2% each. Conclusions: Completion rates were higher for shorter 10 questions subject examinations. Users identifying themselves as MD/DO scored higher than other users, averaging 75%. Usage was higher for examinations at the top of the web page menu. Scores achieved suggest that a cohort of serious users fully completing the examinations had sufficient preparation to use them to support their pathology education. PMID:25337431

Klatt, Edward C.

2014-01-01

346

P53 codon 72 Arg/Pro polymorphism and lung cancer risk in Asians: an updated meta-analysis.  

PubMed

The polymorphism of p53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Asians have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on the development of lung cancer. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 %CIs) were calculated to assess this effect. A total of 14 individual studies involving 7,929 cases and 5,924 controls were included into this meta-analysis according to the inclusion criteria. The overall OR for the dominant genetic model indicated that the p53 codon 72 Arg/Pro variant was positively correlated with lung cancer risk (ORArg/Pro + Pro/Pro vs. Arg/Arg = 1.14, 95 %CI 1.07-1.23, P OR < 0.001). Similar results were found in the stratified analysis of population-based studies. The histological types of lung cancer and smoking status seemed to exert no effect on the lung cancer risk. Sensitivity analysis confirmed the stability of the above findings. The updated meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism is a risk factor for lung cancer in the Asian population. However, the potential role of gene-environment interaction in lung cancer susceptibility needs further investigation in future studies with high quality. PMID:23812725

Wang, Siyang; Lan, Xingang; Tan, Sheng; Wang, Siwen; Li, Yu

2013-10-01

347

Novel codon insert in HIV type 1 clade B reverse transcriptase associated with low-level viremia during antiretroviral therapy.  

PubMed

We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach. PMID:24020934

Chaillon, Antoine; Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C; Richman, Douglas D; Smith, Davey M

2014-02-01

348

The 129 codon polymorphism of the Prion Protein gene influences earlier cognitive performance in Down syndrome subjects  

Microsoft Academic Search

.   Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at\\u000a codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental\\u000a retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigated the role of the PRNP\\u000a polymorphism in 122 relatively young

Roberto Del Bo; Giacomo Pietro Comi; Roberto Giorda; Marco Crimi; Federica Locatelli; Filippo Martinelli-Boneschi; Uberto Pozzoli; Enrico Castelli; Nereo Bresolin; Guglielmo Scarlato

2003-01-01

349

Autosomal-dominant Alzheimer's disease mutations at the same codon of amyloid precursor protein differentially alter A? production.  

PubMed

Autosomal-dominant Alzheimer's disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes. Studying the mechanisms underlying these mutations can provide insight into the pathways that lead to AD pathology. The majority of biochemical studies on APP mutations to-date have focused on comparing mechanisms between mutations at different codons. It has been assumed that amino acid position is a major determinant of protein dysfunction and clinical phenotype. However, the differential effect of mutations at the same codon has not been sufficiently addressed. In the present study we compared the effects of the aggressive ADAD-associated APP I716F mutation with I716V and I716T on APP processing in human neuroglioma and CHO-K1 cells. All APP I716 mutations increased the ratio of A?42/40 and changed the product line preference of ?-secretase towards A?38 production. In addition, the APP I716F mutation impaired the ?-cleavage and the fourth cleavage of ?-secretase and led to abnormal APP ?-CTF accumulation at the plasma membrane. Taken together, these data indicate that APP mutations at the same codon can induce diverse abnormalities in APP processing, some resembling PSEN1 mutations. These differential effects could explain the clinical differences observed among ADAD patients bearing different APP mutations at the same position. The amyloid precursor protein (APP) I716F mutation is associated with autosomal dominant Alzheimer's disease with the youngest age-at-onset for the APP locus. Here, we describe that this mutation, when compared to two other familial Alzheimer's disease mutations at the same codon (I716V and I716T), interfered distinctly with ?-secretase cleavage. While all three mutations direct ?-secretase cleavage towards the 48?38 production line, the APP I716F mutation also impaired the ?-cleavage and the fourth cleavage of ?-secretase, resembling a PSEN1 mutation. These features may contribute to the aggressiveness of this mutation. PMID:24117942

Suárez-Calvet, Marc; Belbin, Olivia; Pera, Marta; Badiola, Nahuai; Magrané, Jordi; Guardia-Laguarta, Cristina; Muñoz, Laia; Colom-Cadena, Martí; Clarimón, Jordi; Lleó, Alberto

2014-01-01

350

Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population  

Microsoft Academic Search

BACKGROUND: Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D receptor gene in a Japanese population. We also investigated

Yoshiyuki Ban; Matsuo Taniyama; Tatsuo Yanagawa; Satoru Yamada; Taro Maruyama; Akira Kasuga; Yoshio Ban

2001-01-01

351

Improving API Usage through Automatic Detection of Redundant Code  

E-print Network

Improving API Usage through Automatic Detection of Redundant Code David Kawrykow and Martin P Programming Interfaces (APIs). We have observed many cases where APIs are used in ways that are not the most effective. We developed a technique and tool support to automatically detect such patterns of API usage

Robillard, Martin

352

Detecting Inefficient API Usage David Kawrykow and Martin P. Robillard  

E-print Network

Detecting Inefficient API Usage David Kawrykow and Martin P. Robillard School of Computer Science (APIs). We have observed many cases where APIs are used in ways that are not efficient. We developed a technique to automatically detect inefficient API usage in software projects. The main hypothesis underlying

Robillard, Martin

353

A High School Survey Questionnaire of Drug Attitudes and Usage.  

ERIC Educational Resources Information Center

The High School Survey on Drugs was developed to assess the drug attitudes of and usage by high school students. The survey was designed to determine drug usage in a specific geopolitical area and to determine drug education program needs. The questionnaire is easily administered to groups of students. There are three types of questions associated…

Pascale, Pietro J.

354

Modification of drug language usage of primary and neurotic psychopaths  

Microsoft Academic Search

Utilized verbal operant procedures to modify the dialectic drug language usage of 35 primary and 35 neurotic psychopaths toward more conventional word usage. It was predicted that neurotic psychopaths would evidence greater performance gains than primary psychopaths who, according to prevailing theories, should be less responsive to generalized social reinforcers. It was found, however, that primary psychopaths conditioned better than

Ronald M; William H. Craine

1971-01-01

355

Using Other Behaviors in the Study of Adolescent Drug Usage.  

ERIC Educational Resources Information Center

The association between usage of alcohol, cigarettes, marijuana and other behaviors was investigated among ninth graders in 40 schools in Ontario. A sample of 1008 boys and 1040 girls gave information on a range of behaviors and activities. Results indicated that drug usage was strongly associated with delinquent, sexual and social behavior. Both…

Hundleby, John D.

356

Drug Usage At the Secondary and Primary School Levels  

ERIC Educational Resources Information Center

This paper reviews the current literature concerning surveys of drug usage at the secondary and primary levels. It discusses how many elementary level students are fast becoming aware of the issue of drug usage due to personal experience or from interactions with friends or siblings. (Author)

Buechler, Kevin P.

1972-01-01

357

The Relationship between Teacher's Technology Integration Ability and Usage  

ERIC Educational Resources Information Center

Despite a steady supply of equipment and continuous training, teachers' use of computers for instruction seems to be limited. Whether the problem is due to teachers' ability or usage of computers for instruction is not well understood. In order to better understand the role of ability and usage in technology integration, teachers' proficiency of…

Hsu, Shihkuan

2010-01-01

358

KOINOTITES: A Web Usage Mining Tool for Personalization  

E-print Network

KOINOTITES: A Web Usage Mining Tool for Personalization Dimitrios Pierrakos Inst. of Informatics@iit.demokritos.gr SUMMARY This paper presents the Web Usage Mining system KOINOTITES, which uses data mining techniques for the construction of user communities on the Web. User communities model groups of visitors in a Web site, who have

Paliouras, George

359

(Not) Hearing Optional Subjects: The Effects of Pragmatic Usage Preferences  

ERIC Educational Resources Information Center

Previous research has shown that usage preferences (non-categorical constraints on the distribution of syntactic structures) shape many grammatical alternations. In the present study, we show that usage preferences also influence which alternate listeners report hearing when presented with acoustically degraded input. We investigated the English…

Mack, Jennifer E.; Clifton, Charles, Jr.; Frazier, Lyn; Taylor, Patrick V.

2012-01-01

360

Accountable Anonymous Service Usage in Mobile Communication Systems \\Lambda  

E-print Network

Accountable Anonymous Service Usage in Mobile Communication Systems \\Lambda Levente Butty Abstract We introduce a model that allows of anonymous yet accountable service usage in mo­ bile communication systems. This model is based on the introduction of a new business role, called the customer care

Bencsáth, Boldizsár

361

Software Dependability Evaluation Based on Markov Usage Models  

E-print Network

Software Dependability Evaluation Based on Markov Usage Models Walter J. Gutjahr Department for computing optimal state transition probabilities for software tests, based on a Markov usage model; this distribution may also be used in the more general context of structural statistical testing of software

Gutjahr, Walter

362

Furman University Justification of Business Usage of Cell Phone  

E-print Network

Furman University Justification of Business Usage of Cell Phone 1 Name Justification of Business Usage of Cell Phone 2 The type of cell phone coverage must be reasonably workday? Yes_____ No_____ Other business reason that may necessitate use of cell phone, describe

363

A PERSPECTIVE ON USAGE--STANDARD VS. SUBSTANDARD.  

ERIC Educational Resources Information Center

DESPITE EFFORTS TO SUBSTITUTE "DIALECT" FOR "USAGE" IN THE GRAMMARIAN'S VOCABULARY, THERE IS STILL A PLACE FOR THE LATTER TERM, FOR WITHIN ANY DIALECT THERE ARE MANY CHOICES OF FORM, WORD, AND CONSTRUCTION. THE TEACHING OF USAGE CAN BE FOUNDED ON TWO SIMPLE PRINCIPLES--(1) THE EXTENT OF SOCIAL PENALTY FOR USING THE ITEM AND (2) THE FREQUENCY OF…

POOLEY, ROBERT C.

364

Characterizing data usage patterns in a large cellular network  

Microsoft Academic Search

Using heterogeneous data sources collected from one of the largest 3G cellular networks in the US over three months, in this paper we investigate the usage patterns of mobile data users. We observe that data usage across mobile users are highly uneven. Most of the users access data services occasionally, while a small number of heavy users contribute to a

Yu Jin; Nick Duffield; Alexandre Gerber; Patrick Haffner; Wen-Ling Hsu; Guy Jacobson; Subhabrata Sen; Shobha Venkataraman; Zhi-Li Zhang

2012-01-01

365

Emotions as determinants of electric car usage intention  

Microsoft Academic Search

In a sample of 1202 Belgians, the determining factors of the usage intention of an electric car and the differences between early and late usage intention segments are investigated. The Theory of Planned Behaviour (TPB) framework is extended with emotional reactions towards the electric car and car driving in general. Emotions and the attitude towards the electric car are the

Ingrid Moons; Patrick De Pelsmacker

2012-01-01

366

Premarital Contraceptives Usage among Male and Female Adolescents.  

ERIC Educational Resources Information Center

Variables important in predicting female contraception usage were found to be those which involved dyadic commitment, conditions of love, self-esteem, and father's occupation (social class). The best predictors of male contraception usage involved experience in dating and internalization of role models via mother's and father's permissiveness.…

Hornick, Joesph P.; And Others

1979-01-01

367

Reduced usage phase impact using demand side management  

Microsoft Academic Search

Determining whether an appliance should be reused or recycled is an important environmental issue. Reducing the life cycle impact of appliance is paramount. The argument for recycling focuses on the usage phase of appliances accounting for more than 80% of the life cycle impact. In order to deduce what the actual environmental effects of the usage phase, cumulative energy demand

P. Finn; M. O'Connell; C. Fitzpatrick

2011-01-01

368

Similarity measure to identify users' profiles in web usage mining  

E-print Network

Similarity measure to identify users' profiles in web usage mining Firas Abou Latif -- Nicolas information. It makes the website browsing process even harder. This paper addresses the web usage mining-Distributed Stochastic Neighbor Embedding) which allows us to project our data in a two dimensional space. Then we apply

Paris-Sud XI, Université de

369

Addictive, dependent, compulsive? A study of mobile phone usage  

Microsoft Academic Search

In order to address the claims that mobile phone usage is addictive, a study was undertaken to categorize mobile phone usage behaviour based on the underlying motivation. Six categories were identified: addictive, compulsive, dependent, habitual, voluntary and mandatory. A survey of 184 students found that the behaviour cannot be conclusively categorized as any specific type, although there was stronger support

Val Hooper; You Zhou

2007-01-01

370

Understanding Mobile App Usage Patterns Using In-App Advertisements  

E-print Network

Understanding Mobile App Usage Patterns Using In-App Advertisements Alok Tongaonkar1 , Shuaifu Dai2. This has resulted in a growing need of the operators to understand the usage patterns of the mobile apps devices or using fields in the HTTP traffic such as User-Agent to identify the apps in network traces

Song, Dawn

371

Reduction of Utility Usage in a Glyphosate Intermediate (GI) Unit  

E-print Network

Reduction of Utility Usage in a Glyphosate Intermediate (GI) Unit Michael L. Sander Manufacturing Technologist Monsanto Company Luling, Louisiana Plant ABSTRACT The Monsanto Company Luling Plant produces glyphosate intermediate (GI...Reduction of Utility Usage in a Glyphosate Intermediate (GI) Unit Michael L. Sander Manufacturing Technologist Monsanto Company Luling, Louisiana Plant ABSTRACT The Monsanto Company Luling Plant produces glyphosate intermediate (GI...

Sander, M. L.

2006-01-01

372

The Effect of Social Influence on The Bloggers' Usage Intention  

Microsoft Academic Search

Purpose – The objective of this paper is to further explore relationships among social influence, blog platform qualities and usage intention for improving the understanding of the effect that social influence exerts on bloggers' usage intention. Design\\/methodology\\/approach – Based on the IS success model, the authors propose a conceptual framework incorporating information quality, system quality, blog function quality and social

Shu-ming Wang; Judy Chuan-Chuan Lin

2011-01-01

373

Personalized Power Saving Profiles Generation Analyzing Smart Device Usage Patterns  

E-print Network

life by almost 90 percent. Some related privacy issues are also addressed and privacy preserving usage; Privacy; Usage pattern. I. INTRODUCTION The Android smartphones and tablets are being adopted feature powerful CPU, HD camera, various sensors and GPS. The application developers exploit the features

Gesbert, David

374

An Overview of Anonymity Technology Usage Bingdong Lia  

E-print Network

information such as the IP address. Due to privacy concerns and other factors, usage of anonymity technologiesAn Overview of Anonymity Technology Usage Bingdong Lia , Esra Erdina , Mehmet Hadi Gunesa, , George Abstract Anonymity technologies enable Internet users to maintain a level of pri- vacy that prevents

Gunes, Mehmet Hadi

375

An Analysis of Anonymity Technology Usage Bingdong Li1  

E-print Network

An Analysis of Anonymity Technology Usage Bingdong Li1 , Esra Erdin1 , Mehmet Hadi G¨une¸s1 criminals to hide themselves. In this paper, we provide usage and geo-location analysis of major to maintain a level of privacy that prevents the collection of identifying information such as the IP address

Gunes, Mehmet Hadi

376

Towards usage control models: beyond traditional access control  

Microsoft Academic Search

In this paper we develop the concept of Usage Control (UCON) that encompasses traditional access control, trust management, and digital rights management and goes beyond them in its definition and scope. While usage control concepts have been mentioned off and on in the security literature for some time, there has been no systematic treatment so far. By unifying these three

Jaehong Park; Ravi S. Sandhu

2002-01-01

377

A Cognitive Radio Approach for Usage of Virtual Unlicensed Spectrum  

Microsoft Academic Search

While essentially all of the frequency spectrum is allocated to different applications, observations provide evidence that usage of the spectrum is actually quite limited, particularly in bands above 3 GHz. In this paper we present a Cognitive Radio approach for usage of Virtual Unlicensed Spectrum (CORVUS), a vision of a Cognitive Radio (CR) based approach that uses allocated spectrum in

Shridhar Mubaraq Mishra; Daniel Willkomm; Robert Brodersen; Adam Wolisz

2005-01-01

378

A Genetic Algorithm Approach to Focused Software Usage Testing  

E-print Network

A Genetic Algorithm Approach to Focused Software Usage Testing Robert M. Patton, Annie S. Wu Orlando, FL, U.S.A. ABSTRACT Because software system testing typically consists of only a very small the test results from a limited amount of testing based on high-level usage models. It can also be very

Wu, Annie S.

379

Query suggestions for mobile search: understanding usage patterns  

Microsoft Academic Search

Entering search terms on mobile phones is a time consuming and cumbersome task. In this paper, we explore the usage patterns of query entry interfaces that display suggestions. Our primary goal is to build a usage model of query suggestions in order to provide user interface guidelines for mobile text prediction interfaces. We find that users who were asked to

Maryam Kamvar; Shumeet Baluja

2008-01-01

380

Codon modification for the DNA sequence of a single-chain Fv antibody against clenbuterol and expression in Pichia pastoris.  

PubMed

The expression efficiency was improved for the recombinant single-chain variable fragment (scFv) against clenbuterol (CBL) obtained from mouse and expressed in the methylotrophic yeast Pichia pastoris GS115, by redesigning and synthesizing the DNA sequence encoding for CBL-scFv based on the codon bias of P. pastoris. The codons encoding 124 amino acids were optimized, in which a total of 156 nucleotides were changed, and the G+C ratio was simultaneously decreased from 53 to 47.2 %. Under the optimized expression conditions, the yield of the recombinant CBL-scFv (41 kDa) antibodies was 0.223 g L?¹ in shake culture. Compared to the non-optimized control, the expression level of the optimized recombinant CBL-scFv based on preferred codons in P. pastoris demonstrated a 2.35-fold higher yield. Furthermore, the recombinant CBL-scFv was purified by Ni-NTA column chromatography, and the purity was 95 %. The purified CBL-scFv showed good CBL recognition by a competitive indirect enzyme-linked immunoassay. The average concentration required for 50 % inhibition of binding and the limit of detection for the assay were 5.82 and 0.77 ng mL?¹, respectively. PMID:24190495

Dong, Jie-Xian; Xie, Xi; Hu, Da-Wei; Chen, Shu-Chi; He, Yong-Sheng; Beier, Ross C; Shen, Yu-Dong; Sun, Yuan-Ming; Xu, Zhen-Lin; Wang, Hong; Yang, Jin-Yi

2014-04-01

381

Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie.  

PubMed

The association between PRNP variation and scrapie incidence was investigated in a highly affected Greek goat herd. Four mutations were identified at codons 171Q/R, 211R/Q, 222Q/K and 240P/S. Lysine at codon 222 was found to be associated with the protection from natural scrapie (P=0.0111). Glutamine at codon 211 was observed in eight animals, all of them being scrapie-negative, indicating a possible protective role of this polymorphism although statistical analysis failed to support it (P=0.1074). A positive association (P=0.0457) between scrapie-affected goats and the wild-type Q(171)R(211)Q(222)S(240) allele is presented for the first time. In addition, a novel R(171)RQS allele, which is identical to the A(136)R(154)R(171) allele that has been associated with resistance to classical scrapie in sheep, was observed in low frequency. Resistant alleles that include K(222) and Q(211) are absent or rare in sheep and can provide the basis for the development of a feasible breeding programme for scrapie eradication in goats. PMID:20107013

Bouzalas, Ilias G; Dovas, Chrysostomos I; Banos, Georgios; Papanastasopoulou, Maria; Kritas, Spyridon; Oevermann, Anna; Papakostaki, Dimitra; Evangelia, Chatzinasiou; Papadopoulos, Orestis; Seuberlich, Torsten; Koptopoulos, Georgios

2010-06-01

382

Phylotranscriptomics: Saturated Third Codon Positions Radically Influence the Estimation of Trees Based on Next-Gen Data  

PubMed Central

Recent advancements in molecular sequencing techniques have led to a surge in the number of phylogenetic studies that incorporate large amounts of genetic data. We test the assumption that analyzing large number of genes will lead to improvements in tree resolution and branch support using moths in the superfamily Bombycoidea, a group with some interfamilial relationships that have been difficult to resolve. Specifically, we use a next-gen data set that included 19 taxa and 938 genes (?1.2M bp) to examine how codon position and saturation might influence resolution and node support among three key families. Maximum likelihood, parsimony, and species tree analysis using gene tree parsimony, on different nucleotide and amino acid data sets, resulted in largely congruent topologies with high bootstrap support compared with prior studies that included fewer loci. However, for a few shallow nodes, nucleotide and amino acid data provided high support for conflicting relationships. The third codon position was saturated and phylogenetic analysis of this position alone supported a completely different, potentially misleading sister group relationship. We used the program RADICAL to assess the number of genes needed to fix some of these difficult nodes. One such node originally needed a total of 850 genes but only required 250 when synonymous signal was removed. Our study shows that, in order to effectively use next-gen data to correctly resolve difficult phylogenetic relationships, it is necessary to assess the effects of synonymous substitutions and third codon positions. PMID:24148944

Breinholt, Jesse W.; Kawahara, Akito Y.

2013-01-01

383

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau.  

PubMed

Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau. PMID:24297887

Zhao, Yang; Ren, Ji-Long; Wang, Ming-Yang; Zhang, Sheng-Ting; Liu, Yu; Li, Min; Cao, Yi-Bin; Zu, Hu-Yue; Chen, Xiao-Cheng; Wu, Chung-I; Nevo, Eviatar; Chen, Xue-Qun; Du, Ji-Zeng

2013-12-17

384

Simplifying tool usage in teleoperative tasks  

NASA Astrophysics Data System (ADS)

Modern robotic research has presented the opportunity for enhanced teleoperative systems. Teleprogramming has been developed for teleoperation in time-delayed environments, but can also lead to increased productivity in non-delayed teleoperation. Powered tools are used to increase the abilities of the remote manipulator. However, tools add to the complexity of the system, both in terms of control and sensing. Teleprogramming can be used to simplify the operators interaction with the manipulator/tool system. Further, the adaptive sensing algorithm of the remote site system (using an instrumented compliant wrist for feedback) simplifies the sensory requirements of the system. Current remote-site implementation of a teleprogramming tool-usage strategy that simplifies tool use is described in this document. The use of powered tools in teleoperation tasks is illustrated by two examples, one using an air-powered impact wrench, and the other using an electric winch. Both of these tools are implemented at our remote site workcell, consisting of a Puma 560 robot working on the task of removing the top of a large box.

Lindsay, Thomas; Paul, Richard P.

1993-03-01

385

Effect Of A Marijuana Drug-Education Program: Comparison of Faculty-Elicited and Student-Elicited Data  

ERIC Educational Resources Information Center

This study examines the effects of a drug education course upon the relationship between drug attitudes and usage, and the validity of attitude-usage relationships, through a comparison of data elicited by peers and teachers. Questionnaires given to students before and after a course indicated significant shifts in attitude-usage patterns. (Author)

Ebel, H. C.; And Others

1975-01-01

386

Orthogonality and Codon Preference of the Pyrrolysyl-tRNA Synthetase-tRNAPyl pair in Escherichia coli for the Genetic Code Expansion  

E-print Network

Systematic studies of basal nonsense suppression, orthogonality of tRNAPyl variants, and cross recognition between codons and tRNA anticodons are reported. E. coli displays detectable basal amber and opal suppression but shows a negligible ochre...

Odoi, Keturah

2012-07-16

387

Generalization method of relationships among nucleotide sequences reveals an order in assimilation of amino acid codons during the isoacceptor tRNAs evolution  

SciTech Connect

A new method, generalization of relationships among the nucleotide sequences, has been used to analyze divergency both within and across the families of isoaccepting tRNAs. Dendrogram, depicting relations between tRNA sets with different amino acid specificities, presents the results of analysis. The method made it possible to interpret the dendrogram, as a reflection of final stage of the evolution of ambiguous molecules-adaptors to highly specific tRNAs. We have proposed a model of amino acid codons assimilation at this stage. According to the model, the final formation of specific adaptors was followed by assimilation of codon clusters (four codons, differing in the third position), the first dinucleotides of which were connected by transitions. Alternate steps along double-stranded coding DNA accompanied the establishment of tRNA sets with strict specificities. Complementary codons, to which specific adaptors were assigned at step the last, were involved into the process afterwards. 34 refs., 2 figs., 1 tab.

Chaley, M.B.; Korotkov, E.V. [Center Bioengineering, Moscow (Russian Federation)

1996-12-31

388

Codon optimization of cry1Ab gene for hyper expression in plant organelles.  

PubMed

With the advent of genetic manipulation techniques, it has become possible to clone and insert gene into the genome of crop plants to confer resistance to insects and pests. Resistance to insects has been demonstrating in transgenic plants either by triggering defense system of plants or by expressing heterologous cry genes for delta-endotoxins from Bacillus thuringiensis. In the present study, synthetic cry1Ab gene was developed with optimized chloroplast preferred codons and is expressed in tobacco plastid genome called plastome, following chloroplast transformation strategy, which is environment friendly technique to minimize out-crossing of transgenes to related weeds and crops. In addition, due to high polyploidy of plastid genome transformation of chloroplast permits the introduction of thousands of copies of foreign genes per plant cell, leading to extraordinarily high levels of foreign protein expression. The chloroplast transformation technology aims to insert stably into the plastome through homologous recombination into pre-decided position. To characterize the synthetic cry1Ab gene, chloroplast transformation vectors were developed and bombarded to the leaf cells of tobacco plants maintained under aseptic conditions. After bombardment, the drug resistant shoots were selected and regenerated on drug containing regeneration medium. Homoplasmic shoots were recovered after successive rounds of selection and regeneration. Proliferated plants were subjected to genomic DNA analysis by using polymerase chain reaction (PCR) technique where cry1Ab gene-specific primers were used. PCR positive plants were subjected to protein analysis, and functionally expressed proteins were detected using Immuno-Strips specific for cry1Ab/Ac gene products. Transgenic plants carrying cry1Ab gene were found expressing Bt toxins confirming that engineered gene could be expressed in other plants as well. PMID:19757171

Jabeen, Rasheda; Khan, Muhammad Sarwar; Zafar, Yusuf; Anjum, Tehmina

2010-02-01

389

Successful expression and purification of DPPD using a codon optimized synthetic gene*  

PubMed Central

DPPD (Rv0061) is a difficult to express protein of Mycobacterium tuberculosis that elicits strong and specific delayed type hypersensitivity reactions in humans infected with M. tuberculosis. Therefore e DPPD is a molecule that can improve the specificity of the tuberculin skin test, which is widely used as an aid for the diagnosis of tuberculosis. However, a pitfall of our initial studies was that the DPPD molecule used to perform the skin tests was engineered as fusion molecule with another Mycobacterium protein. This approach was used because no expression of DPPD could be achieved either as a single molecule or as a fusion protein using a variety of commercially available expression systems. Here, we report the production and purification of rDPPD using a synthetic gene engineered to contain E. coli codon bias. The gene was cloned into pET14b expression vector, which was subsequently used to transform Rosetta 2(DE3) pLysS or BL-21(DE3)pLysS host cells. The recombinant protein was over-expressed after induction with IPTG and its purification was easily achieved at levels of 5 – 10 mg/l of bacterial broth cultures. The purified protein was confirmed to be DPPD by Mass Spectroscopy sequencing analysis. Moreover, purified rDPPD stimulated peripheral blood mononuclear cells of PPD positive blood donors to produce high levels of IFN-?, thus confirming that this molecule is biologically active. Because of the DPPD gene is restricted to the tuberculosis-complex organisms of Mycobacterium genus, this highly purified molecule should be useful for the identification of individuals sensitized with tubercle bacilli. PMID:23264930

Kashino, Suely S.; Campos-Neto, Antonio

2012-01-01

390

Association of vitamin D receptor gene start codon (Fok1) polymorphism with high myopia  

PubMed Central

Background: High myopia caused primarily due to abnormal emmetropization and excessive axial ocular elongation is associated with sight-threatening ocular pathology. Muscular dysfunction of ocular ciliary muscles due to altered intracellular calcium levels can result in defective mechanotransduction of the eye and retinal defocus. The vitamin D3 receptor (VDR; a intracellular hormone receptor) is known to mediate calcium homeostasis, influencing the development of myopia. Materials and Methods: In the present study, a total of 206 high myopia, 98 low myopia and 250 control samples were analyzed for VDR gene Fok1 (exon 2 start codon) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: High myopia patients revealed decrease in the frequency of ff homozygotes (8.3%) as compared to control group (14.0%), with a corresponding increase in frequency of FF homozygotes (68.9% in high myopia vs. 62.8% in controls). The frequency of f allele carriers (Ff and ff) was increased in females of high myopia (35.6%) and low myopia cases (45.4%). Elevated frequency of f allele was found only in early age at onset cases of high myopia (0.227) and later age at onset (10–20 years) cases of low myopia (0.273) as well as in low myopia cases with parental consanguinity (0.458) (P 0.035; ?2 = 6.692*). Conclusion: The results suggest that VDR gene might not be playing a direct role in the development of myopia, but might contribute indirectly to the risk conferred by mechanical stress factors or growth/development related factors through its role in calcium homeostasis and regulation of ciliary muscle function. PMID:21897619

Annamaneni, Sandhya; Bindu, Chintala Hema; Reddy, Kasu Prasad; Vishnupriya, Satti

2011-01-01

391

The presence of codon-anticodon pairs in the acceptor stem of tRNAs.  

PubMed Central

A total of 1268 available (excluding mitochondrial) tRNA sequences was used to reconstruct the common consensus image of their acceptor domains. Its structure appeared as a 11-bp-long double-stranded palindrome with complementary triplets in the center, each flanked by the 3'-ACCD and NGGU-5' motifs on each strand (D, base determinator). The palindrome readily extends up to the modern tRNA-like cloverleaf passing through an intermediate hairpin having in the center the single-stranded triplet, in supplement to its double-stranded precursor. The latter might represent an original anticodon-codon pair mapped at 1-2-3 positions of the present-day tRNA acceptors. This conclusion is supported by the striking correlation: in pairs of consensus tRNAs with complementary anticodons, their bases at the 2nd position of the acceptor stem were also complementary. Accordingly, inverse complementarity was also evident at the 71st position of the acceptor stem. With a single exception (tRNA(Phe)-tRNA(Glu) pair), the parallelism is especially impressive for the pairs of tRNAs recognized by aminoacyl-tRNA synthetases (aaRS) from the opposite classes. The above complementarity still doubly presented at the key central position of real single-stranded anticodons and their hypothetical double-stranded precursors is consistent with our previous data pointing to the double-strand use of ancient RNAs in the origin of the main actors in translation- tRNAs with complementary anticodons and the two classes of aaRS. Images Fig. 3 Table 2 Fig. 4 PMID:8643439

Rodin, S; Rodin, A; Ohno, S

1996-01-01

392

Analytical expression of the purine/pyrimidine codon probability after and before random mutations.  

PubMed

Recently, we proposed a new model of DNA sequence evolution (Arquès and Michel. 1990b. Bull. math. Biol. 52, 741-772) according to which actual genes on the purine/pyrimidine (R/Y) alphabet (R = purine = adenine or guanine, Y = pyrimidine = cytosine or thymine) are the result of two successive evolutionary genetic processes: (i) a mixing (independent) process of non-random oligonucleotides (words of base length less than 10: YRY(N)6, YRYRYR and YRYYRY are so far identified; N = R or Y) leading to primitive genes (words of several hundreds of base length) and followed by (ii) a random mutation process, i.e., transformations of a base R (respectively Y) into the base Y (respectively R) at random sites in these primitive genes. Following this model the problem investigated here is the study of the variation of the 8 R/Y codon probabilities RRR, ..., YYY under random mutations. Two analytical expressions solved here allow analysis of this variation in the classical evolutionary sense (from the past to the present, i.e., after random mutations), but also in the inverted evolutionary sense (from the present to the past, i.e., before random mutations). Different properties are also derived from these formulae. Finally, a few applications of these formulae are presented. They prove the proposition in Arquès and Michel (1990b. Bull. math. Biol. 52, 741-772), Section 3.3.2, with the existence of a maximal mean number of random mutations per base of the order 0.3 in the protein coding genes. They also confirm the mixing process of oligonucleotides by excluding the purine/pyrimidine contiguous and alternating tracts from the formation process of primitive genes. PMID:8281128

Arquès, D G; Michel, C J

1993-11-01

393

Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo  

Microsoft Academic Search

Selection of the AUG start codon is a key step in translation initiation requiring hydrolysis of GTP in the eIF2•GTPMet-tRNAi Met ternary complex (TC) and subsequent Pi release from eIF2•GDPPi. It is thought that eIF1 prevents recognition of non-AUGs by promoting scanning and blocking Pi release at non-AUG codons. We show that Suimutations in Saccharomyces cerevisiae eIF1, which increase initiation

Yuen-Nei Cheung; David Maag; Sarah F. Mitchell; Christie A. Fekete; Mikkel A. Algire; Julie E. Takacs; Nikolay Shirokikh; Tatyana Pestova; Jon R. Lorsch; Alan G. Hinnebusch

2007-01-01

394

Life without tRNAArg-adenosine deaminase TadA: evolutionary consequences of decoding the four CGN codons as arginine in Mycoplasmas and other Mollicutes  

PubMed Central

In most bacteria, two tRNAs decode the four arginine CGN codons. One tRNA harboring a wobble inosine (tRNAArgICG) reads the CGU, CGC and CGA codons, whereas a second tRNA harboring a wobble cytidine (tRNAArgCCG) reads the remaining CGG codon. The reduced genomes of Mycoplasmas and other Mollicutes lack the gene encoding tRNAArgCCG. This raises the question of how these organisms decode CGG codons. Examination of 36 Mollicute genomes for genes encoding tRNAArg and the TadA enzyme, responsible for wobble inosine formation, suggested an evolutionary scenario where tadA gene mutations first occurred. This allowed the temporary accumulation of non-deaminated tRNAArgACG, capable of reading all CGN codons. This hypothesis was verified in Mycoplasma capricolum, which contains a small fraction of tRNAArgACG with a non-deaminated wobble adenosine. Subsets of Mollicutes continued to evolve by losing both the mutated tRNAArgCCG and tadA, and then acquired a new tRNAArgUCG. This permitted further tRNAArgACG mutations with tRNAArgGCG or its disappearance, leaving a single tRNAArgUCG to decode the four CGN codons. The key point of our model is that the A-to-I deamination activity had to be controlled before the loss of the tadA gene, allowing the stepwise evolution of Mollicutes toward an alternative decoding strategy. PMID:23658230

Yokobori, Shin-ichi; Kitamura, Aya; Grosjean, Henri; Bessho, Yoshitaka

2013-01-01

395

Toward a rationale for the PTC124 (Ataluren) promoted readthrough of premature stop codons: a computational approach and GFP-reporter cell-based assay.  

PubMed

The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination codons by using a new reporter. The reporter vector was based on a plasmid harboring the H2B histone coding sequence fused in frame with the green fluorescent protein (GFP) cDNA, and a TGA stop codon was introduced in the H2B-GFP gene by site-directed mutagenesis. Additionally, an unprecedented computational study on the putative supramolecular interaction between PTC124 and an 11-codon (33-nucleotides) sequence corresponding to a CFTR mRNA fragment containing a central UGA nonsense mutation showed a specific interaction between PTC124 and the UGA codon. Altogether, the H2B-GFP-opal based assay and the molecular dynamics (MD) simulation support the hypothesis that PTC124 is able to promote the specific readthrough of internal TGA premature stop codons. PMID:24483936

Lentini, Laura; Melfi, Raffaella; Di Leonardo, Aldo; Spinello, Angelo; Barone, Giampaolo; Pace, Andrea; Palumbo Piccionello, Antonio; Pibiri, Ivana

2014-03-01

396

Specific VpU codon changes were significantly associated with gp120 V3 tropic signatures in HIV-1 B-subtype.  

PubMed

After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env (gp120 and gp41) and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-1 infection process begins when the gp120 subunit of the envelope glycoprotein complex interacts with its receptor(s) on the target cell. The V3 domain of gp120 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIV-1 isolates, sequences from the VpU to V3 regions (119 in R5- and 120 X4-tropic viruses; one per patient) were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gp120(V3) signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures (R5-viruses: S11, E25D; X4-viruses: S11KR, E25KRQ), other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters: one associated with R5-tropic sequences (bootstrap=0.94), involving: (a) H13NP(V3), E25D(V3), S11(V3), T22A(V3) and Q61H(VpU), (b) E25A(V3) and L12F(VpU), (c) D44E(VpU), R18Q(V3) and D80N(VpU); and another associated with X4-tropic sequences (bootstrap=0.97), involving: (i) E25I(V3) and V10A(VpU), (ii) 0-1insV(VpU), H13R(V3), I46L(VpU), I30M(V3) and 60-62del(VpU), (iii) S11KR(V3) and E25KRQ(V3). Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-1 tropism. PMID:23271577

Dimonte, Salvatore; Babakir-Mina, Muhammed; Aquaro, Stefano; Perno, Carlo-Federico

2012-12-01

397

Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies  

PubMed Central

Background: Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. Methods: We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1–infected humanized mice treated with the antibody PGT128 and from untreated control mice. Results: For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1–infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). Conclusions: These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach. PMID:25072615

Walter, Hauke; Lengauer, Thomas

2014-01-01

398

Modelling of word usage frequency dynamics using artificial neural network  

NASA Astrophysics Data System (ADS)

In this paper the method for modelling of word usage frequency time series is proposed. An artificial feedforward neural network was used to predict word usage frequencies. The neural network was trained using the maximum likelihood criterion. The Google Books Ngram corpus was used for the analysis. This database provides a large amount of data on frequency of specific word forms for 7 languages. Statistical modelling of word usage frequency time series allows finding optimal fitting and filtering algorithm for subsequent lexicographic analysis and verification of frequency trend models.

Maslennikova, Yu S.; Bochkarev, V. V.; Voloskov, D. S.

2014-03-01

399

Sex differences in perceptions of pain coping strategy usage.  

PubMed

Sex differences are generally found in the perception and experience of pain, with women reporting more intense and frequent pain than men. One reason why such differences may occur has been linked to socially-acquired gender-role expectations associated with pain. Although there is evidence that men and women report using different pain coping strategies, we do not know the extent to which gender-specific expectations are associated with pain-related coping. The current study sought to examine this in more detail by administering a standard pain coping measures on three separate occasions, but with different instructions. Hundred and twenty two participants (57 male, 65 female) were asked to complete the coping measure as themselves, then again as they would expect the typical man and the typical woman to complete it. Results indicated that there were no significant differences between men and women in their own self-reported usage of pain coping strategies. However, there was general evidence to suggest that there are differences in stereotypical views of how men and women are thought to cope with pain. Furthermore, sex differences were also found in how participants viewed their own coping behaviours in comparison to that of the typical man and typical woman. These results confirm that alongside pain, men and women hold different gender-specific expectations with respect to certain pain coping strategies. Future research is required to examine whether these different coping expectations influence an individuals own choice of strategy, and whether this in turn affects actual pain experiences. PMID:18762439

Keogh, Edmund; Denford, Sarah

2009-07-01

400

A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus  

PubMed Central

Background The major hurdle in the treatment of Human Immunodeficiency virus type 1 (HIV-1) includes the development of drug resistance-associated mutations in the target regions of the virus. Since reverse transcriptase (RT) is essential for HIV-1 replication, several nucleoside analogues have been developed to target RT of the virus. Clinical studies have shown that mutations at RT codon 65 and 74 which are located in ?3-?4 linkage group of finger sub-domain of RT are selected during treatment with several RT inhibitors, including didanosine, deoxycytidine, abacavir and tenofovir. Interestingly, the co-selection of K65R and L74V is rare in clinical settings. We have previously shown that K65R and L74V are incompatible and a R?K reversion occurs at codon 65 during replication of the virus. Analysis of the HIV resistance database has revealed that similar to K65R+L74V, the double mutant K65R+L74I is also rare. We sought to compare the impact of L?V versus L?I change at codon 74 in the background of K65R mutation, on the replication of doubly mutant viruses. Methods Proviral clones containing K65R, L74V, L74I, K65R+L74V and K65R+L74I RT mutations were created in pNL4-3 backbone and viruses were produced in 293T cells. Replication efficiencies of all the viruses were compared in peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication capacity (RC) of mutant viruses in relation to wild type was calculated on the basis of antigen p24 production and RT activity, and paired analysis by student t-test was performed among RCs of doubly mutant viruses. Reversion at RT codons 65 and 74 was monitored during replication in PBM cells. In vitro processivity of mutant RTs was measured to analyze the impact of amino acid changes at RT codon 74. Results Replication kinetics plot showed that all of the mutant viruses were attenuated as compared to wild type (WT) virus. Although attenuated in comparison to WT virus and single point mutants K65R, L74V and L74I; the double mutant K65R+L74I replicated efficiently in comparison to K65R+L74V mutant. The increased replication capacity of K65R+L74I viruses in comparison to K65R+L74V viruses was significant at multiplicity of infection 0.01 (p = 0.0004). Direct sequencing and sequencing after population cloning showed a more pronounced reversion at codon 65 in viruses containing K65R+L74V mutations in comparison to viruses with K65R+L74I mutations. In vitro processivity assays showed increased processivity of RT containing K65R+L74I in comparison to K65R+L74V RT. Conclusions The improved replication kinetics of K65R+L74I virus in comparison to K65R+L74V viruses was due to an increase in the processivity of RT containing K65R+L74I mutations. These observations support the rationale behind structural functional analysis to understand the interactions among unique RT mutations that may emerge during the treatment with specific drug regimens. PMID:21255423

2011-01-01

401

Comparison of the haemolysin secretion protein HlyB from Proteus vulgaris and Escherichia coli ; site-directed mutagenesis causing impairment of export function  

Microsoft Academic Search

The hlyB secretion genes of Proteus vulgaris and Escherichia coli showed 81% nucleotide homology and similar E. coli-atypical codon usage. The deduced protein sequences differed in 54 of 707 residues and shared a previously unreported sequence which corresponds to the ATP-binding motif characteristic of protein kinases. The motif was also conserved in the HlyB of Morganella morganii. Of 4 oligonucleotide-directed

Vassilis Koronakis; Eva Koronakis; Colin Hughes

1988-01-01

402

A semantically enriched web usage based recommendation model  

E-print Network

With the rapid growth of internet technologies, Web has become a huge repository of information and keeps growing exponentially under no editorial control. However the human capability to read, access and understand Web content remains constant. This motivated researchers to provide Web personalized online services such as Web recommendations to alleviate the information overload problem and provide tailored Web experiences to the Web users. Recent studies show that Web usage mining has emerged as a popular approach in providing Web personalization. However conventional Web usage based recommender systems are limited in their ability to use the domain knowledge of the Web application. The focus is only on Web usage data. As a consequence the quality of the discovered patterns is low. In this paper, we propose a novel framework integrating semantic information in the Web usage mining process. Sequential Pattern Mining technique is applied over the semantic space to discover the frequent sequential patterns. Th...

Ramesh, C; Govardhan, A

2011-01-01

403

SNSs usage among Chinese internet users: an empirical study.  

PubMed

Renren and Kaixin, which are Chinese versions of "Facebook", are the main Social Network Sites (SNSs) in China. Although many researchers have been exploring SNSs usage and have gained rich results, there are limited studies for the understanding of SNSs usage in China. In this present study, with 777 Chinese participants, we test variables influencing Chinese SNSs usage based on the technology acceptance model (TAM). Using structural equation modeling techniques, the empirical results confirm that the perceived ease of use significantly determines the perceived usefulness, which in turn influences SNSs use intensity. Meanwhile, the Internet self-efficacy could affect perceived ease of use and further determine SNSs use intensity indirectly. Overall, our results could be used to describe and predict SNSs usage among Chinese Internet users. PMID:20543288

Shi, Junqi; Niu, Qikun

2010-01-01

404

Memory Usage Inference for Object-Oriented Programs  

E-print Network

We present a type-based approach to statically derive symbolic closed-form formulae that characterize the bounds of heap memory usages of programs written in object-oriented languages. Given a program with size and alias ...

Nguyen, Huu Hai

405

The silent codon change I507-ATC->ATT contributes to the severity of the ?F508 CFTR channel dysfunction  

PubMed Central

The most common disease-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is the out-of-frame deletion of 3 nucleotides (CTT). This mutation leads to the loss of phenylalanine-508 (?F508) and a silent codon change (SCC) for isoleucine-507 (I507-ATC?ATT). ?F508 CFTR is misfolded and degraded by endoplasmic reticulum-associated degradation (ERAD). We have demonstrated that the I507-ATC?ATT SCC alters ?F508 CFTR mRNA structure and translation dynamics. By comparing the biochemical and functional properties of the I507-ATT and I507-ATC ?F508 CFTR, we establish that the I507-ATC?ATT SCC contributes to the cotranslational misfolding, ERAD, and to the functional defects associated with ?F508 CFTR. We demonstrate that the I507-ATC ?F508 CFTR is less susceptible to the ER quality-control machinery during translation than the I507-ATT, although 27°C correction is necessary for sufficient cell-surface expression. Whole-cell patch-clamp recordings indicate sustained, thermally stable cAMP-activated Cl? transport through I507-ATC and unstable function of the I507-ATT ?F508 CFTR. Single-channel recordings reveal improved gating properties of the I507-ATC compared to I507-ATT ?F508 CFTR (NPo=0.45±0.037 vs. NPo=0.09±0.002; P<0.001). Our results signify the role of the I507-ATC?ATT SCC in the ?F508 CFTR defects and support the importance of synonymous codon choices in determining the function of gene products.—Lazrak, A., Fu, L., Bali, V., Bartoszewski, R., Rab, A., Havasi, V., Keiles, S., Kappes, J., Kumar, R., Lefkowitz, E., Sorscher, E. J., Matalon, S., Collawn, J. F., Bebok, Z. The silent codon change I507-ATC?ATT contributes to the severity of the ?F508 CFTR. PMID:23907436

Lazrak, Ahmed; Fu, Lianwu; Bali, Vedrana; Bartoszewski, Rafal; Rab, Andras; Havasi, Viktoria; Keiles, Steve; Kappes, John; Kumar, Ranjit; Lefkowitz, Elliot; Sorscher, Eric J.; Matalon, Sadis; Collawn, James F.; Bebok, Zsuzsanna

2013-01-01

406

tRNASer(CGA) differentially regulates expression of wild-type and codon-modified papillomavirus L1 genes  

PubMed Central

Exogenous transfer RNAs (tRNAs) favor translation of bovine papillomavirus 1 wild-type (wt) L1 mRNA in in vitro translation systems (Zhou et al. 1999, J. Virol., 73, 4972–4982). We, therefore, investigated whether papillomavirus (PV) wt L1 protein expression could be enhanced in eukaryotic cells following exogenous tRNA supplementation. Both Chinese hamster ovary (CHO) and Cos1 cells, transfected with PV1 wt L1 genes, effectively transcribed the genes but did not translate them. However, L1 protein translation was demonstrated following co-transfection with the L1 gene and a gene expressing tRNASer(CGA). Cell lines, stably transfected with a bovine papillomavirus 1 (BPV1) wt L1 expression construct, produced L1 protein after the transfection of the tRNASer(CGA) gene, but not following the transfection with basal vectors, suggesting that tRNASer(CGA) gene enhanced wt L1 translation as a result of endogenous tRNA alterations and phosphorylation of translation initiation factors elF4E and elF2? in the tRNASer(CGA) transfected L1 cell lines. The tRNASer(CGA) gene expression significantly reduced translation of L1 proteins expressed from codon-modified (HB) PV L1 genes utilizing mammalian preferred codons, but had variable effects on translation of green fluorescent proteins (GFPs) expressed from six serine GFP variants. The changes of tRNA pools appear to match the codon composition of PV wt and HB L1 genes and serine GFP variants to regulate translation of their mRNAs. These findings demonstrate for the first time in eukaryotic cells that translation of the target genes can be differentially influenced by the provision of a single tRNA expression construct. PMID:15319446

Gu, Wenyi; Li, Mengrong; Zhao, Wei Ming; Fang, Ning Xia; Bu, Shurui; Frazer, Ian H.; Zhao, Kong-Nan

2004-01-01

407

Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria.  

PubMed

Release factors (RFs) govern the termination phase of protein synthesis. Human mitochondria harbor four different members of the class 1 RF family: RF1Lmt/mtRF1a, RF1mt, C12orf65 and ICT1. The homolog of the essential ICT1 factor is widely distributed in bacteria and organelles and has the peculiar feature in human mitochondria to be part of the ribosome as a ribosomal protein of the large subunit. The factor has been suggested to rescue stalled ribosomes in a codon-independent manner. The mechanism of action of this factor was obscure and is addressed here. Using a homologous mitochondria system of purified components, we demonstrate that the integrated ICT1 has no rescue activity. Rather, purified ICT1 binds stoichiometrically to mitochondrial ribosomes in addition to the integrated copy and functions as a general rescue factor, i.e. it releases the polypeptide from the peptidyl tRNA from ribosomes stalled at the end or in the middle of an mRNA or even from non-programmed ribosomes. The data suggest that the unusual termination at a sense codon (AGA/G) of the oxidative-phosphorylation enzymes CO1 and ND6 is also performed by ICT1 challenging a previous model, according to which RF1Lmt/mtRF1a is responsible for the translation termination at non-standard stop codons. We also demonstrate by mutational analyses that the unique insertion sequence present in the N-terminal domain of ICT1 is essential for peptide release rather than for ribosome binding. The function of RF1mt, another member of the class1 RFs in mammalian mitochondria, was also examined and is discussed. PMID:25233460

Akabane, Shiori; Ueda, Takuya; Nierhaus, Knud H; Takeuchi, Nono

2014-09-01

408

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

SciTech Connect

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.

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

1996-04-01

409

Social Media Usage in Indian Information Technology Professionals  

E-print Network

Social media usage has grown by leaps and bound over the last decade and has become an important platform being used by the workforce for both work and non-work related purposes. The usage of these tools varies across employees and organizations depending on multiple factors. The present study examines the social media usage at workplace in Information Technology professionals by measuring it on the basis of their usage, pride in using, routine of use, and belongingness to the social media community. Social media usage intensity is analyzed for various employee groups. These groups are categorized on the basis of – social media accessibility at workplace, smart phone availability, gender of employees, employee age group, managerial level, highest educational qualification, and city of residence of employees. A questionnaire was completed for around 400 users and the data was analyzed utilizing descriptive statistics, t tests, and one-way ANOVA. The results indicated that usage of social media varied for some of these employee groups.

unknown authors

410

Modulation of Stop Codon Read-Through Efficiency and Its Effect on the Replication of Murine Leukemia Virus  

PubMed Central

ABSTRACT Translational readthrough—suppression of termination at a stop codon—is exploited in the replication cycles of several viruses and represents a potential target for antiviral intervention. In the gammaretroviruses, typified by Moloney murine leukemia virus (MuLV), gag and pol are in the same reading frame, separated by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-Pol fusion protein. Here, we investigated the effect on MuLV replication of modulating readthrough efficiency. We began by manipulating the readthrough signal in the context of an infectious viral clone to generate a series of MuLV variants in which readthrough was stimulated or reduced. In carefully controlled infectivity assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defect and that a 10-fold reduction essentially abolished replication. However, up to an ?8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus. These high levels of readthrough were achieved using a two-plasmid system, with Gag and Gag-Pol expressed from separate infectious clones. We also modulated readthrough by silencing expression of eukaryotic release factors 1 and 3 (eRF1 and eRF3) or by introducing aminoglycosides into the cells. The data obtained indicate that gammaretroviruses tolerate a substantial excess of viral Gag-Pol synthesis but are very sensitive to a reduction in levels of this polyprotein. Thus, as is also the case for ribosomal frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the most beneficial. IMPORTANCE Many pathogenic RNA viruses and retroviruses use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase enzymes. These translational “recoding” processes are potential targets for antiviral intervention, but we have only a limited understanding of the consequences to virus replication of modulating the efficiency of recoding, particularly for those viruses employing readthrough. In this paper, we describe the first systematic analysis of the effect of increasing or decreasing readthrough efficiency on virus replication using the gammaretrovirus MuLV as a model system. We find unexpectedly that MuLV replication is only slightly inhibited by substantial increases in readthrough frequency, but as with other viruses that use recoding strategies, replication is quite sensitive to even modest reductions. These studies provide insights into both the readthrough process and MuLV replication and have implications for the selection of antivirals against gammaretroviruses. PMID:24991001

Csibra, Eszter; Brierley, Ian

2014-01-01

411

Transcription attenuation-mediated control of leu operon expression: influence of the number of Leu control codons.  

PubMed Central

Four adjacent Leu codons within the leu leader RNA are critically important in transcription attenuation-mediated control of leu operon expression in Salmonella typhimurium and Escherichia coli (P. W. Carter, D. L. Weiss, H. L. Weith, and J. M. Calvo, J. Bacteriol. 162:943-949, 1985). The leader region from S. typhimurium was altered by site-directed mutagenesis to produce constructs having between one and seven adjacent Leu codons, all CUA. leu operon expression was measured in strains containing six of these constructs, each integrated into the chromosome in a single copy. Operon expression was sufficiently high that all strains grew in minimal medium unsupplemented by leucine. Expression of the operon was measured in strains cultured in such a way that their growth was limited by the intracellular concentration of either leucine or of leucyl-tRNA. In general, the leu operon for each construct responded similarly to the parent construct in terms of the degree of expression as a function of the degree of limitation. However, a strain containing (CUA)1 and, to a certain extent, a strain having (CUA)2 responded somewhat more sluggishly and strains containing (CUA)6 and (CUA)7 responded more sensitively to limitations than did the parent construct. In addition, DNA fragments containing the leu promoter and leader region were used as templates in in vitro transcription reactions employing purified RNA polymerase. With nucleoside triphosphate concentrations of 200 microM, RNA polymerase paused during transcription of the leu leader region at a site about 95 bp downstream from the site of transcription initiation. The halftimes of the pause were 1 min at 37 degrees C and 3 min at 22 degrees C. The pause was lengthened substantially when the GTP concentration was lowered to 20 micromoles. Our results are interpreted most easily in terms of an all-or-none model. Given two Leu control codons, the operon responds with nearly maximum output over a wide range of leucine limitation, and that outcome does not change much with increasing numbers of control codons. Images PMID:1999384

Bartkus, J M; Tyler, B; Calvo, J M

1991-01-01

412

Comparisons of infant Escherichia coli isolates link genomic profiles with adaptation to the ecological niche  

PubMed Central

Background Despite being one of the most intensely studied model organisms, many questions still remain about the evolutionary biology and ecology of Escherichia coli. An important step toward achieving a more complete understanding of E.coli biology entails elucidating relationships between gene content and adaptation to the ecological niche. Results Here, we present genome comparisons of 16 E.coli strains that represent commensals and pathogens isolated from infants during a specific time period in Trondheim, Norway. Using differential gene content, we characterized enrichment profiles of the collection of strains relating to phylogeny, early vs. late colonization, pathogenicity and growth rate. We found clear gene content distinctions relating to the various grouping criteria. We also found that different categories of strains use different genetic elements for similar biological processes. The sequenced genomes included two pairs of strains where each pair was isolated from the same infant at different time points. One pair, in which the strains were isolated four months apart, showed maintenance of an early colonizer genome profile but also gene content and codon usage changes toward the late colonizer profile. Lastly, we placed our sequenced isolates into a broader genomic context by comparing them with 25 published E.coli genomes that represent a variety of pathotypes and commensal strains. This analysis demonstrated the importance of geography in shaping strain level gene content profiles. Conclusions Our results indicate a general pattern where alternative genetic pathways lead toward a consistent ecological role for E.coli as a species. Within this framework however, we saw selection shaping the coding repertoire of E.coli strains toward distinct ecotypes with different phenotypic properties. PMID:23384204

2013-01-01

413

A real-time polymerase chain reaction assay to detect single nucleotide polymorphisms at codon 171 in the prion gene for the genotyping of scrapie susceptibility in sheep.  

PubMed

The objective of this study was to report a reliable real-time polymerase chain reaction assay compatible with the Roche LightCycler 2.0 capable of genotyping sheep for scrapie susceptibility at codon 171. The single nucleotide polymorphisms (SNPs) in the prion protein gene in sheep that may govern resistance to scrapie at codon 171 encode for lysine (K), histidine (H), glutamine (Q), and arginine (R). A modified proteinase K method for leukocytes or whole blood was used to isolate genomic DNA from sheep blood. Fluoresentric developed and optimized primers and probes for the codon 171 SNP assay. The assay was initially validated using 218 determinations from whole blood of known genotypes with 100% correct identity. The assay was further validated through a whole-blood check test provided annually by the National Veterinary Services Laboratory with a correct identification rate of 100%. From January 2005 to December 2006, 3,672 samples from blood were genotyped at codon 171. The genotypes were QR(171) (n = 1,838, 50.05%), RR(171) (n = 1,423, 38.75%), QQ(171) (n = 407, 11.08%), HR(171) (n = 2, 0.05%), and HQ(171) (n = 2, 0.05%). The combination of this simple extraction method and the novel Fluoresentric assay is very accurate, is capable of identifying all 4 SNPs at codon 171 in one reaction, and has proven to be a useful tool for producers in their selective breeding programs. PMID:18319434

McKay, Jerome T; Brigner, Tiffany A; Caplin, Brian E; McCurdy, Kimberly S; Forde, Richard L

2008-03-01

414

Cryptic MHC class I-binding peptides are revealed by aminoglycoside-induced stop codon read-through into the 3? UTR  

PubMed Central

Aminoglycosides have been proposed as therapies for genetic disorders caused by nonsense mutations, because of their capacity to enhance translational read-through of premature termination codons (PTCs), thereby permitting expression of functional full-length protein. However, a potential consequence of this strategy is the development of an autoimmune response to HLA-presented epitopes encoded downstream of the PTC or other stop codons. Using a recombinant virus-expression system in tissue culture and in mice, we demonstrate that gentamicin can induce expression and MHC class I presentation of a model epitope encoded downstream of a PTC at levels sufficient to activate CD8+ T cells. The degree of read-through–derived peptide presentation varies with the sequence of the stop codon and +1 nucleotide. Additionally, we applied a mass spectrometry exploration of the HLA class I peptide repertoire of gentamicin-treated cells and identified multiple peptides derived from read-through of conventional stop codons. These results substantiate the possibility of self-reactivity to cryptic epitopes revealed by stop codon read-through therapies and potentially other therapeutic approaches involving compounds that alter translational fidelity. PMID:24706797

Goodenough, Elliot; Robinson, Tara M.; Zook, Matthew B.; Flanigan, Kevin M.; Atkins, John F.; Howard, Michael T.; Eisenlohr, Laurence C.

2014-01-01

415

Sequence-specific DNA alkylation targeting for Kras codon 13 mutation by pyrrole-imidazole polyamide seco-CBI conjugates.  

PubMed

Hairpin N-methylpyrrole-N-methylimidazole polyamide seco-CBI conjugates 2-6 were designed for synthesis by Fmoc solid-phase synthesis, and their DNA-alkylating activities against the Kras codon?13 mutation were compared by high-resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards the Kras codon?13 mutation site, with alkylation occurring at the A of the sequence 5'-ACGTCACCA-3' (site?2), including minor 1?bp-mismatch alkylation against wild type 5'-ACGCCACCA-3' (site?3). Conjugate 6, which differs from conjugate 5 by exchanging one Py unit with a ? unit, showed high selectivity but only weakly alkylated the A of 5'-ACGTCACCA-3' (site?2). The hairpin polyamide seco-CBI conjugate 5 thus alkylates according to Dervan's pairing rule with the pairing recognition which ?/? pair targets T-A and A-T pairs. SPR and a computer-minimized model suggest that 5 binds to the target sequence with high affinity in a hairpin conformation, allowing for efficient DNA alkylation. PMID:24382626

Taylor, Rhys Dylan; Asamitsu, Sefan; Takenaka, Tomohiro; Yamamoto, Makoto; Hashiya, Kaori; Kawamoto, Yusuke; Bando, Toshikazu; Nagase, Hiroki; Sugiyama, Hiroshi

2014-01-27

416

Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay.  

PubMed

Dominant mutations in the gene encoding the mRNA splicing factor PRPF31 cause retinitis pigmentosa, a hereditary form of retinal degeneration. Most of these mutations are characterized by DNA changes that lead to premature termination codons. We investigated 6 different PRPF31 mutations, represented by single-base substitutions or microdeletions, in cell lines derived from 9 patients with dominant retinitis pigmentosa. Five of these mutations lead to premature termination codons, and 1 leads to the skipping of exon 2. Allele-specific measurement of PRPF31 transcripts revealed a strong reduction in the expression of mutant alleles. As a consequence, total PRPF31 protein abundance was decreased, and no truncated proteins were detected. Subnuclear localization of the full-length PRPF31 that was present remained unaffected. Blocking nonsense-mediated mRNA decay significantly restored the amount of mutant PRPF31 mRNA but did not restore the synthesis of mutant proteins, even in conjunction with inhibitors of protein degradation pathways. Our results indicate that most PRPF31 mutations ultimately result in null alleles through the activation of surveillance mechanisms that inactivate mutant mRNA and, possibly, proteins. Furthermore, these data provide compelling evidence that the pathogenic effect of PRPF31 mutations is likely due to haploinsufficiency rather than to gain of function. PMID:18317597

Rio Frio, Thomas; Wade, Nicholas M; Ransijn, Adriana; Berson, Eliot L; Beckmann, Jacques S; Rivolta, Carlo

2008-04-01

417

A system of RNA modifications and biased codon use controls cellular stress response at the level of translation.  

PubMed

Cells respond to environmental stressors and xenobiotic exposures using regulatory networks to control gene expression, and there is an emerging appreciation for the role of numerous postsynthetic chemical modifications of DNA, RNA, and proteins in controlling transcription and translation of the stress response. In this Perspective, we present a model for a new network that regulates the cellular response to xenobiotic exposures and other stresses in which stress-induced reprogramming of a system of dozens of post-transcriptional modifications on tRNA (tRNA) promotes selective translation of codon-biased mRNAs for critical response proteins. As a product of novel genomic and bioanalytical technologies, this model has strong parallels with the regulatory networks of DNA methylation in epigenetics and the variety of protein secondary modifications comprising signaling pathways and the histone code. When present at the tRNA wobble position, the modified ribonucleosides enhance the translation of mRNAs in which the cognate codons of the tRNAs are highly over-represented and that represent critical stress response proteins. A parallel system may also downregulate the translation of families of proteins. Notably, dysregulation of the tRNA methyltransferase enzymes in humans has also been implicated in cancer etiology, with demonstrated oncogenic and tumor-suppressive effects. PMID:24422464

Dedon, Peter C; Begley, Thomas J

2014-03-17

418

Isoelectrofocusing phenotype and relative concentration of transcobalamin II isoproteins related to the codon 259 Arg/Pro polymorphism.  

PubMed

We investigated transcobalamin II (TC) isoelectrofocusing (IEF) phenotype and codon 259 polymorphism, in Caco-2 and HT-29 cells and in blood drawn from 39 healthy Caucasians. Caco-2 cells expressed a single TC variant (259-Arg), while HT-29 cells expressed TC with either Arg or Pro at codon 259 and exhibited two isoproteins in IEF with urea, but only one in IEF without urea. Among the Caucasians, 7 subjects expressed the TC 259-Arg variant, 10 the 259-Pro variant, and 22 were heterozygous. The TC 259-Pro isoprotein issued from HT-29 cells and heterozygous caucasian sera, was, respectively, 2. 4-fold and 1.6-fold higher than the TC 259-Arg isoprotein. Apo-TC and vitamin B12 serum concentrations in 259-Pro homozygotes were, respectively, 1.7 and 1.4-fold higher than those in 259-Arg homozygotes (p<0.005 and p=0.05). In conclusion, the 259-Arg/Pro polymorphism yields two TC variants only titratable in denaturing conditions and affects the blood level of both Apo-TC and vitamin B12. PMID:9790985

Namour, F; Guy, M; Aimone-Gastin, I; de Nonancourt, M; Mrabet, N; Guéant, J L

1998-10-29

419

Detection of codon 12 K- ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas  

PubMed Central

K- ras activation by point mutation in codon 12 has been reported in lung adenocarcinomas in various models of experimental lung tumours induced by chemical carcinogens. The hypothesis of the presence of cells containing K- ras mutation in non neoplastic bronchial carina, the main site of impaction of airborne contaminants, was investigated by evaluating concurrent lung tumour and non-neoplastic proximal bronchial carinae from 19 patients with lung adenocarcinomas. The restriction fragment length polymorphism enriched PCR method used can detect one mutant allele among 103normal alleles. A mutation was detected in 42% of lung adenocarcinoma samples. No mutation was detected in either tumour or bronchial carinae in nine patients (47%). K- ras mutation was detected in the lung tumour but not in bronchial carinae in four patients (21%), in both the lung tumour and bronchial carinae in four other patients (21%). In two patients (11%), K- ras mutation was detected in at least one bronchial carina, but not in the lung tumour. Mutations of codon 12, confirmed by sequencing analysis of ten samples, were G to T transversion, mostly TGT and GTT in bronchial carinae and lung tumours. Our data show that activated K- ras by point mutation can be present in non-neoplastic bronchial carina mucosa even when no mutation is detected in tumour samples. © 2000 Cancer Research Campaign PMID:10646897

Urban, T; Ricci, S; Danel, C; Antoine, M; Kambouchner, M; Godard, V; Lacave, R; Bernaudin, J-F

2000-01-01

420

Mannose-Binding Lectin Codon 54 Gene Polymorphism and Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis  

PubMed Central

Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10–11.15; P for heterogeneity = 0.013; I2 = 68.6%) and 12.68 (95% CI 3.74–42.92; P for heterogeneity = 0.932, I2 = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29–5.12; P for heterogeneity = 0.897; I2 = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women's innate immunity in response to Candida. PMID:25143944

Nedovic, Bojan; Posteraro, Brunella; Leoncini, Emanuele; Amore, Rosarita; Sanguinetti, Maurizio; Boccia, Stefania

2014-01-01