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Sample records for relative codon adaptation

  1. Codon Adaptation of Plastid Genes

    PubMed Central

    Suzuki, Haruo; Morton, Brian R.

    2016-01-01

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

  2. A major controversy in codon-anticodon adaptation resolved by a new codon usage index.

    PubMed

    Xia, Xuhua

    2015-02-01

    Two alternative hypotheses attribute different benefits to codon-anticodon adaptation. The first assumes that protein production is rate limited by both initiation and elongation and that codon-anticodon adaptation would result in higher elongation efficiency and more efficient and accurate protein production, especially for highly expressed genes. The second claims that protein production is rate limited only by initiation efficiency but that improved codon adaptation and, consequently, increased elongation efficiency have the benefit of increasing ribosomal availability for global translation. To test these hypotheses, a recent study engineered a synthetic library of 154 genes, all encoding the same protein but differing in degrees of codon adaptation, to quantify the effect of differential codon adaptation on protein production in Escherichia coli. The surprising conclusion that "codon bias did not correlate with gene expression" and that "translation initiation, not elongation, is rate-limiting for gene expression" contradicts the conclusion reached by many other empirical studies. In this paper, I resolve the contradiction by reanalyzing the data from the 154 sequences. I demonstrate that translation elongation accounts for about 17% of total variation in protein production and that the previous conclusion is due to the use of a codon adaptation index (CAI) that does not account for the mutation bias in characterizing codon adaptation. The effect of translation elongation becomes undetectable only when translation initiation is unrealistically slow. A new index of translation elongation ITE is formulated to facilitate studies on the efficiency and evolution of the translation machinery.

  3. Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the Hosts

    PubMed Central

    Wang, Hongju; Liu, Siqing; Zhang, Bo

    2016-01-01

    Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators. The results indicate that the codon usage bias of ZIKV is relatively low. Several lines of evidence support the hypothesis that translational selection plays a role in shaping the codon usage pattern of ZIKV. The results from a correspondence analysis (CA) indicate that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV and its hosts suggest that ZIKV tends to evolve codon usage patterns that are comparable to those of its hosts. Moreover, selection pressure from Homo sapiens on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes aegypti and Aedes albopictus. Taken together, both natural translational selection and mutation pressure are important for shaping the codon usage pattern of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its adaption to its hosts. PMID:27893824

  4. Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development.

    PubMed

    Goñi, Natalia; Iriarte, Andrés; Comas, Victoria; Soñora, Martín; Moreno, Pilar; Moratorio, Gonzalo; Musto, Héctor; Cristina, Juan

    2012-11-08

    Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.

  5. Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development

    PubMed Central

    2012-01-01

    Background Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. Results We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. Conclusions A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines. PMID:23134595

  6. Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon.

    PubMed

    Katz, M J; Gándara, L; De Lella Ezcurra, A L; Wappner, P

    2016-05-01

    Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress.

  7. Genome-wide analysis reveals class and gene specific codon usage adaptation in avian paramyxoviruses 1

    USDA-ARS?s Scientific Manuscript database

    In order to characterize the evolutionary adaptations of avian paramyxovirus 1 (APMV-1) genomes, we have compared codon usage and codon adaptation indexes among groups of Newcastle disease viruses that differ in biological, ecological, and genetic characteristics. We have used available GenBank com...

  8. Measuring and Detecting Molecular Adaptation in Codon Usage Against Nonsense Errors During Protein Translation

    PubMed Central

    Gilchrist, Michael A.; Shah, Premal; Zaretzki, Russell

    2009-01-01

    Codon usage bias (CUB) has been documented across a wide range of taxa and is the subject of numerous studies. While most explanations of CUB invoke some type of natural selection, most measures of CUB adaptation are heuristically defined. In contrast, we present a novel and mechanistic method for defining and contextualizing CUB adaptation to reduce the cost of nonsense errors during protein translation. Using a model of protein translation, we develop a general approach for measuring the protein production cost in the face of nonsense errors of a given allele as well as the mean and variance of these costs across its coding synonyms. We then use these results to define the nonsense error adaptation index (NAI) of the allele or a contiguous subset thereof. Conceptually, the NAI value of an allele is a relative measure of its elevation on a specific and well-defined adaptive landscape. To illustrate its utility, we calculate NAI values for the entire coding sequence and across a set of nonoverlapping windows for each gene in the Saccharomyces cerevisiae S288c genome. Our results provide clear evidence of adaptation to reduce the cost of nonsense errors and increasing adaptation with codon position and expression. The magnitude and nature of this adaptation are also largely consistent with simulation results in which nonsense errors are the only selective force driving CUB evolution. Because NAI is derived from mechanistic models, it is both easier to interpret and more amenable to future refinement than other commonly used measures of codon bias. Further, our approach can also be used as a starting point for developing other mechanistically derived measures of adaptation such as for translational accuracy. PMID:19822731

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

    PubMed

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

    2016-10-01

    Actinobacteria are Gram-positive bacteria commonly found in soil, freshwater and marine ecosystems. In this investigation, bias in codon usages of ninety actinobacterial genomes was analyzed by estimating different indices of codon bias such as Nc (effective number of codons), SCUO (synonymous codon usage order), RSCU (relative synonymous codon usage), as well as sequence patterns of codon contexts. The results revealed several characteristic features of codon usage in Actinobacteria, as follows: 1) C- or G-ending codons are used frequently in comparison with A- and U ending codons; 2) there is a direct relationship of GC content with use of specific amino acids such as alanine, proline and glycine; 3) there is an inverse relationship between GC content and Nc estimates, 4) there is low SCUO value (<0.5) for most genes; and 5) GCC-GCC, GCC-GGC, GCC-GAG and CUC-GAC are the frequent context sequences among codons. This study highlights the fact that: 1) in Actinobacteria, extreme GC content and codon bias are driven by mutation rather than natural selection; (2) traits like aerobicity are associated with effective natural selection and therefore low GC content and low codon bias, demonstrating the role of both mutational bias and translational selection in shaping the habitat and phenotype of actinobacterial species. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Optimizing heterologous expression in Dictyostelium: importance of 5′ codon adaptation

    PubMed Central

    Vervoort, Elisa B.; van Ravestein, Arno; van Peij, Noël N. M. E.; Heikoop, Judith C.; van Haastert, Peter J. M.; Verheijden, Gijs F.; Linskens, Maarten H. K.

    2000-01-01

    Expression of heterologous proteins in Dictyostelium discoideum presents unique research opportunities, such as the functional analysis of complex human glycoproteins after random mutagenesis. In one study, human chorionic gonadotropin (hCG) and human follicle stimulating hormone were expressed in Dictyostelium. During the course of these experiments, we also investigated the role of codon usage and of the DNA sequence upstream of the ATG start codon. The Dictyostelium genome has a higher AT content than the human, resulting in a different codon preference. The hCG-β gene contains three clusters with infrequently used codons that were changed to codons that are preferred by Dictyostelium. The results reported here show that optimizing the first 5–17 codons of the hCG gene contributes to 4- to 5-fold increased expression levels, but that further optimization has no significant effect. These observations suggest that optimal codon usage contributes to ribosome stabilization, but does not play an important role during the elongation phase of translation. Furthermore, adapting the 5′-sequence of the hCG gene to the Dictyostelium ‘Kozak’-like sequence increased expression levels ~1.5-fold. Thus, using both codon optimization and ‘Kozak’ adaptation, a 6- to 8-fold increase in expression levels could be obtained for hCG. PMID:10773074

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

    PubMed Central

    Morton, B R

    2001-01-01

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

  12. Genomic adaptation of the ISA virus to Salmo salar codon usage

    PubMed Central

    2013-01-01

    Background The ISA virus (ISAV) is an Orthomyxovirus whose genome encodes for at least 10 proteins. Low protein identity and lack of genetic tools have hampered the study of the molecular mechanism behind its virulence. It has been shown that viral codon usage controls several processes such as translational efficiency, folding, tuning of protein expression, antigenicity and virulence. Despite this, the possible role that adaptation to host codon usage plays in virulence and viral evolution has not been studied in ISAV. Methods Intergenomic adaptation between viral and host genomes was calculated using the codon adaptation index score with EMBOSS software and the Kazusa database. Classification of host genes according to GeneOnthology was performed using Blast2go. A non parametric test was applied to determine the presence of significant correlations among CAI, mortality and time. Results Using the codon adaptation index (CAI) score, we found that the encoding genes for nucleoprotein, matrix protein M1 and antagonist of Interferon I signaling (NS1) are the ISAV genes that are more adapted to host codon usage, in agreement with their requirement for production of viral particles and inactivation of antiviral responses. Comparison to host genes showed that ISAV shares CAI values with less than 0.45% of Salmo salar genes. GeneOntology classification of host genes showed that ISAV genes share CAI values with genes from less than 3% of the host biological process, far from the 14% shown by Influenza A viruses and closer to the 5% shown by Influenza B and C. As well, we identified a positive correlation (p<0.05) between CAI values of a virus and the duration of the outbreak disease in given salmon farms, as well as a weak relationship between codon adaptation values of PB1 and the mortality rates of a set of ISA viruses. Conclusions Our analysis shows that ISAV is the least adapted viral Salmo salar pathogen and Orthomyxovirus family member less adapted to host codon

  13. Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau

    PubMed Central

    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

    2013-01-01

    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

  14. Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences

    PubMed Central

    Bahir, Iris; Fromer, Menachem; Prat, Yosef; Linial, Michal

    2009-01-01

    Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria-infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host-specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed. PMID:19888206

  15. A theoretical analysis of codon adaptation index of the Boophilus microplus bm86 gene directed to the optimization of a DNA vaccine.

    PubMed

    Ruiz, Lina María; Armengol, Gemma; Habeych, Edwin; Orduz, Sergio

    2006-04-21

    DNA vaccines utilize host cell molecules for gene transcription and translation to proteins, and the interspecific difference of codon usage is one of the major obstacles for effective induction of specific and strong immune response. In an attempt to improve codon usage effects of DNA vaccine on protein expression, a quantitative study was conducted to clarify the relationship of codon usage in the tick gene bm86 and its potential expression in bovine cells. The calculated relative synonymous codon usage (RSCU) and codon adaptation index (CAI) values of bm86 from Boophilus microplus and a set of 14 highly expressed genes from Bos taurus indicated that some codons utilized frequently in bm86 are rarely used in B. taurus genes and vice versa. The different translational efficiencies obtained suggested that after DNA vaccination using the wild bm86 gene, the protein Bm86 would be expressed in bovines, but it would not be the optimum sequence. However, using the codon-optimized bm86 gene to bovines, whose sequence was theoretically designed, would probably improve the level of the immune response generated against ticks.

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

    PubMed Central

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

    2006-01-01

    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

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

    PubMed

    Parto, Sahar; Lartillot, Nicolas

    2017-06-23

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

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

    PubMed

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

    2014-08-10

    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 α and β 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 α and β 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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-11-01

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

  20. High codon adaptation in citrus tristeza virus to its citrus host.

    PubMed

    Cheng, Xiao-fei; Wu, Xiao-yun; Wang, Hui-zhong; Sun, Yu-qiang; Qian, Yong-sheng; Luo, Lu

    2012-06-14

    Citrus tristeza virus (CTV), a member of the genus Closterovirus within the family Closteroviridae, is the causal agent of citrus tristeza disease. Previous studies revealed that the negative selection, RNA recombination and gene flow were the most important forces that drove CTV evolution. However, the CTV codon usage was not studied and thus its role in CTV evolution remains unknown. A detailed comparative analysis of CTV codon usage pattern was done in this study. Results of the study show that although in general CTV does not have a high degree of codon usage bias, the codon usage of CTV has a high level of resemblance to its host codon usage. In addition, our data indicate that the codon usage resemblance is only observed for the woody plant-infecting closteroviruses but not the closteroviruses infecting the herbaceous host plants, suggesting the existence of different virus-host interactions between the herbaceous plant-infecting and woody plant-infecting closteroviruses. Based on the results, we suggest that in addition to RNA recombination, negative selection and gene flow, host plant codon usage selection can also affect CTV evolution.

  1. High codon adaptation in citrus tristeza virus to its citrus host

    PubMed Central

    2012-01-01

    Background Citrus tristeza virus (CTV), a member of the genus Closterovirus within the family Closteroviridae, is the causal agent of citrus tristeza disease. Previous studies revealed that the negative selection, RNA recombination and gene flow were the most important forces that drove CTV evolution. However, the CTV codon usage was not studied and thus its role in CTV evolution remains unknown. Results A detailed comparative analysis of CTV codon usage pattern was done in this study. Results of the study show that although in general CTV does not have a high degree of codon usage bias, the codon usage of CTV has a high level of resemblance to its host codon usage. In addition, our data indicate that the codon usage resemblance is only observed for the woody plant-infecting closteroviruses but not the closteroviruses infecting the herbaceous host plants, suggesting the existence of different virus-host interactions between the herbaceous plant-infecting and woody plant-infecting closteroviruses. Conclusion Based on the results, we suggest that in addition to RNA recombination, negative selection and gene flow, host plant codon usage selection can also affect CTV evolution. PMID:22698086

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

    PubMed Central

    Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

    2009-01-01

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

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

    PubMed

    Singh, Niraj K; Tyagi, Anuj

    2017-03-21

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

  4. Clustering of low usage codons in the translation initiation region of hepatitis C virus.

    PubMed

    Zhou, Jian-hua; Su, Jun-hong; Chen, Hao-tai; Zhang, Jie; Ma, Li-na; Ding, Yao-zhong; Stipkovits, Laszlo; Szathmary, Susan; Pejsak, Zygmunt; Liu, Yong-sheng

    2013-08-01

    The adaptation of the overall codon usage pattern of hepatitis C virus (HCV) to that of human is estimated by the synonymous codon usage value (RSCU). The synonymous codon usage biases for the translation initiation region (TIR) of this virus are also analyzed by calculation of usage fluctuation of each synonymous codon along the TIR (the first 30 codon sites of the whole coding sequence of HCV). As for the overall codon usage pattern of HCV, this virus has a significant tendency to delete the codons with CpG or TpA dinucleotides. Turning to the adaptation of the overall codon usage of HCV to that of human, over half part of codons has a similar usage pattern between this virus and human, suggesting that the host cellular environment of the overall codon usage pattern influences the formation of codon usage for HCV. In addition, there is no obvious phenomenon that the codons with relatively low energy tend to be highly selected in the TIR of HCV, suggesting that the synonymous codon usage patterns for the TIR of HCV might be not affected by the secondary structure of nucleotide sequence, however, the formation of synonymous codons usage in the TIR of HCV is influenced by the overall codon usage patterns of human to some degree.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Analysis of codon usage bias of mitochondrial genome in Bombyx mori and its relation to evolution.

    PubMed

    Wei, Lei; He, Jian; Jia, Xian; Qi, Qi; Liang, Zhisheng; Zheng, Hao; Ping, Yao; Liu, Shuyu; Sun, Jingchen

    2014-12-17

    Synonymous codon usage bias (SCUB) is an inevitable phenomenon in organismic taxa, generally referring to differences in the occurrence frequency of codons across different species or within the genome of the same species. SCUB happens in various degrees under pressure from nature selection, mutation bias and other factors in different ways. It also attaches great significance to gene expression and species evolution, however, a systematic investigation towards the codon usage in Bombyx mori (B. mori) has not been reported yet. Moreover, it is still indistinct about the reasons contributing to the bias or the relationship between the bias and the evolution of B. mori. The comparison of the codon usage pattern between the genomic DNA (gDNA) and the mitochondrial DNA (mtDNA) from B. mori suggests that mtDNA has a higher level of codon bias. Furthermore, the correspondence analysis suggests that natural selection, such as gene length, gene function and translational selection, dominates the codon preference of mtDNA, while the composition constraints for mutation bias only plays a minor role. Additionally, the clustering results of the silkworm superfamily suggest a lack of explicitness in the relationship between the codon usage of mitogenome and species evolution. Among the complicated influence factors leading to codon bias, natural selection is found to play a major role in shaping the high bias in the mtDNA of B. mori from our current data. Although the cluster analysis reveals that codon bias correlates little with the species evolution, furthermore, a detailed analysis of codon usage of mitogenome provides better insight into the evolutionary relationships in Lepidoptera. However, more new methods and data are needed to investigate the relationship between the mtDNA bias and evolution.

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

    PubMed

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

    2015-05-26

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

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

    PubMed Central

    Bhatia, Sandeep; Sood, Richa; Selvaraj, Pavulraj

    2016-01-01

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

  10. Codon optimization underpins generalist parasitism in fungi

    PubMed Central

    Badet, Thomas; Peyraud, Remi; Mbengue, Malick; Navaud, Olivier; Derbyshire, Mark; Oliver, Richard P; Barbacci, Adelin; Raffaele, Sylvain

    2017-01-01

    The range of hosts that parasites can infect is a key determinant of the emergence and spread of disease. Yet, the impact of host range variation on the evolution of parasite genomes remains unknown. Here, we show that codon optimization underlies genome adaptation in broad host range parasites. We found that the longer proteins encoded by broad host range fungi likely increase natural selection on codon optimization in these species. Accordingly, codon optimization correlates with host range across the fungal kingdom. At the species level, biased patterns of synonymous substitutions underpin increased codon optimization in a generalist but not a specialist fungal pathogen. Virulence genes were consistently enriched in highly codon-optimized genes of generalist but not specialist species. We conclude that codon optimization is related to the capacity of parasites to colonize multiple hosts. Our results link genome evolution and translational regulation to the long-term persistence of generalist parasitism. DOI: http://dx.doi.org/10.7554/eLife.22472.001 PMID:28157073

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

    PubMed Central

    Tong, Yigang

    2014-01-01

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

  12. The polymorphism of XRCC3 codon 241 and AFB1-related hepatocellular carcinoma in Guangxi population, China.

    PubMed

    Long, Xi Dai; Ma, Yun; Qu, De Ying; Liu, Yun Guang; Huang, Zhao Quan; Huang, Yong Zhi; Lin, Zhong Hui; Wei, Ni Bo; Zhou, Shu Chun

    2008-07-01

    The relationship between aflatoxin B1 (AFB1) exposure and hepatocellular carcinoma (HCC) has been previously demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) codon 241 (namely: Thr241Met), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as AFB1, been less well elaborated. We conducted a case-control study including 491 cases and 862 controls to evaluate the associations between this polymorphism and HCC risk for Guangxi population by means of polymerase chain reaction-restriction fragment length polymorphism analysis. We found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of HCC than those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted odds ratios 2.22 and 7.19; 95% confidence intervals 1.72-2.88 and 4.52-11.42, respectively). The risk of HCC, moreover, did appear to differ more significantly among individuals featuring high-level AFB1-DNA adducts, whose adjusted odds ratios (95% confidence intervals) were 11.59 (5.73-23.47) and 37.54 (16.32-86.32), respectively. These findings support the hypothesis that the XRCC3 Thr241Met polymorphism may be associated with the risk of AFB1-related HCC among the Guangxi population.

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

    PubMed Central

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

    2013-01-01

    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

  14. p53 codon 72 polymorphism interactions with dietary and tobacco related habits and risk of stomach cancer in Mizoram, India.

    PubMed

    Malakar, Mridul; Devi, K Rekha; Phukan, Rup Kumar; Kaur, Tanvir; Deka, Manab; Puia, Lalhriat; Sailo, Lalrinliana; Lalhmangaihi, T; Barua, Debajit; Rajguru, Sanjib Kumar; Mahanta, Jagadish; Narain, Kanwar

    2014-01-01

    This study was carried out to investigate the interaction of p53 codon 72 polymorphism, dietary and tobacco habits with reference to risk of stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach cancer cases and 210 age, sex and ethnicity matched healthy population controls were included in this study. The p53 codon 72 polymorphism was detected by PCR-RFLP and sequencing. H. pylori infection status was determined by ELISA. Information on various dietary and tobacco related habits was recorded with a standard questionnaire. This study revealed that overall, the Pro/ Pro genotype was significantly associated with a higher risk of stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype. In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50; 95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2) among older people (>60 years). However, no such associations were observed in males and in individuals <60 years of age. Smoke dried fish and preserved meat (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR, 4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared to non-consumers. Significant gene-environment interactions exist in terms of p53 codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI, 1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21). In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.

  15. The use of the rare UUA codon to define "expression space" for genes involved in secondary metabolism, development and environmental adaptation in streptomyces.

    PubMed

    Chater, Keith F; Chandra, Govind

    2008-02-01

    In Streptomyces coelicolor, bldA encodes the only tRNA for a rare leucine codon, UUA. This tRNA is unnecessary for growth, but is required for some aspects of secondary metabolism and morphological development, as revealed by the phenotypes of bldA mutants in diverse streptomycetes. This article is a comprehensive review of out understanding of this unusual situation. Based on information from four sequenced genomes it now appears that, typically, about 2 approximately 3% of genes in any one streptomycete contain a TTA codon, most having been acquired through species-specific horizontal gene transfer. Among the few widely conserved TTA-containing genes, mutations in just one, the pleiotropic regulatory gene adpA, give an obvious phenotype: such mutants are defective in aerial growth and sporulation, but vary in the extent of their impairment in secondary metabolism in different streptomycetes. The TTA codon in adpA is largely responsible for the morphological phenotype of a bldA mutant of S. coelicolor. AdpA-dependent targets include several genes involved in the integrated action of extracellular proteases that, at least in some species, are involved in the conversion of primary biomass into spores. The effects of bldA mutations on secondary metabolism are mostly attributable to the presence of TTA codons in pathway-specific genes, particularly in transcriptional activator genes. This is not confined to S. coelicolor-it is true for about half of all known antibiotic biosynthetic gene sets from streptomycetes. Combined microarray and proteomic analysis of liquid (and therefore non-sporulating) S. coelicolor bldA mutant cultures revealed effects of the mutation during rapid growth, during transition phase, and in stationary phase. Some of these effects may be secondary consequences of changes in the pattern of ppGpp accumulation. It is argued that the preferential accumulation of the bldA tRNA under conditions in which growth is significantly constrained has evolved

  16. What drives codon choices in human genes?

    PubMed

    Karlin, S; Mrázek, J

    1996-10-04

    Synonymous codon usage is based and the bias seems to be different in different organisms. Factors with proposed roles in causing codon bias include degree and timing of gene expression, codon-anticodon interactions, transcription and translation rate and fidelity, codon context, and global and local G + C content. We offer a new perspective and new methods for elucidating codon choices applied especially to the human genome. We present data supporting the thesis that codon choices for human genes are largely a consequence of two factors: (1) amino acid constraints, (2) maintaining DNA structures dependent on base-step conformational tendencies consistent with the organism's genome signature that is determined by genome-wide processes of DNA modification, replication and repair. The related codon signature defined as the dinucleotide relative abundances at the distinct codon positions (1,2), (2,3), and (3,4) (4 = 1 of the next codon) accommodates both the global genome signature and amino acid constraints. In human genes, codon positions (2,3) and (3,4) containing the silent site have similar codon signatures reflecting DNA symmetry. Strong CG and TA dinucleotide underrepresentation is observed at all codon positions as well as in non-coding regions. Estimates of synonymous codon usage based on codon signatures are in excellent agreement with the actual codon usage in human and general vertebrate genes. These properties are largely independent of the isochore compartment (G + C content), gene size, and transcriptional and translational constraints. We hypothesize that major influences on codon usage in human genes result from residue preferences and diresidue associations in proteins coupled to biases on the DNA level, related to replication and repair processes and/or DNA structural requirements.

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

    PubMed Central

    Wu, Xudong; Li, Guohui

    2016-01-01

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

  18. Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon

    PubMed Central

    Tikkanen, R; Tiihonen, J; Rautiainen, M R; Paunio, T; Bevilacqua, L; Panarsky, R; Goldman, D; Virkkunen, M

    2015-01-01

    A relatively common stop codon (Q20*) was identified in the serotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown–Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption. Regression analyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior. PMID:26575222

  19. Genomic characteristics comparisons of 12 food-related filamentous fungi in tRNA gene set, codon usage and amino acid composition.

    PubMed

    Chen, Wanping; Xie, Ting; Shao, Yanchun; Chen, Fusheng

    2012-04-10

    Filamentous fungi are widely exploited in food industry due to their abilities to secrete large amounts of enzymes and metabolites. The recent availability of fungal genome sequences has provided an opportunity to explore the genomic characteristics of these food-related filamentous fungi. In this paper, we selected 12 representative filamentous fungi in the areas of food processing and safety, which were Aspergillus clavatus, A. flavus, A. fumigatus, A. nidulans, A. niger, A. oryzae, A. terreus, Monascus ruber, Neurospora crassa, Penicillium chrysogenum, Rhizopus oryzae and Trichoderma reesei, and did the comparative studies of their genomic characteristics of tRNA gene distribution, codon usage pattern and amino acid composition. The results showed that the copy numbers greatly differed among isoaccepting tRNA genes and the distribution seemed to be related with translation process. The results also revealed that genome compositional variation probably constrained the base choice at the third codon, and affected the overall amino acid composition but seemed to have little effect on the integrated physicochemical characteristics of overall amino acids. The further analysis suggested that the wobble pairing and base modification were the important mechanisms in codon-anticodon interaction. In the scope of authors' knowledge, it is the first report about the genomic characteristics analysis of food-related filamentous fungi, which would be informative for the analysis of filamentous fungal genome evolution and their practical application in food industry. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among Eukaryotes and present in two Bacterial phyla.

    PubMed

    Rafels-Ybern, Àlbert; Torres, Adrian Gabriel; Grau-Bove, Xavier; Ruiz-Trillo, Iñaki; de Pouplana, Lluís Ribas

    2017-09-07

    The modification of adenosine to inosine at position 34 of tRNA anticodons has a profound impact upon codon-anticodon recognition. In bacteria, I34 is thought to exist only in tRNA(Arg), while in eukaryotes the modification is present in eight different tRNAs. In eukaryotes, the widespread use of I34 strongly influenced the evolution of genomes in terms of tRNA gene abundance and codon usage. In humans, codon usage indicates that I34 modified tRNAs are preferred for the translation of highly repetitive coding sequences, suggesting that I34 is an important modification for the synthesis of proteins of highly skewed amino acid composition. Here we extend the analysis of distribution of codons that are recognized by I34 containing tRNAs to all phyla known to use this modification. We find that the preference for codons recognized by such tRNAs in genes with highly biased codon compositions is universal among eukaryotes, and we report that, unexpectedly, some bacterial phyla show a similar preference. We demonstrate that the genomes of these bacterial species contain previously undescribed tRNA genes that are potential substrates for deamination at position 34.

  1. Estimating selection on synonymous codon usage from noisy experimental data.

    PubMed

    Wallace, Edward W J; Airoldi, Edoardo M; Drummond, D Allan

    2013-06-01

    A key goal in molecular evolution is to extract mechanistic insights from signatures of selection. A case study is codon usage, where despite many recent advances and hypotheses, two longstanding problems remain: the relative contribution of selection and mutation in determining codon frequencies and the relative contribution of translational speed and accuracy to selection. The relevant targets of selection--the rate of translation and of mistranslation of a codon per unit time in the cell--can only be related to mechanistic properties of the translational apparatus if the number of transcripts per cell is known, requiring use of gene expression measurements. Perhaps surprisingly, different gene-expression data sets yield markedly different estimates of selection. We show that this is largely due to measurement noise, notably due to differences between studies rather than instrument error or biological variability. We develop an analytical framework that explicitly models noise in expression in the context of the population-genetic model. Estimates of mutation and selection strength in budding yeast produced by this method are robust to the expression data set used and are substantially higher than estimates using a noise-blind approach. We introduce per-gene selection estimates that correlate well with previous scoring systems, such as the codon adaptation index, while now carrying an evolutionary interpretation. On average, selection for codon usage in budding yeast is weak, yet our estimates show that genes range from virtually unselected to average per-codon selection coefficients above the inverse population size. Our analytical framework may be generally useful for distinguishing biological signals from measurement noise in other applications that depend upon measurements of gene expression.

  2. Synthetic Gene Design Using Codon Optimization On-Line (COOL).

    PubMed

    Yu, Kai; Ang, Kok Siong; Lee, Dong-Yup

    2017-01-01

    Codon optimization has been widely used for designing native or synthetic genes to enhance their expression in heterologous host organisms. We recently developed Codon Optimization On-Line (COOL) which is a web-based tool to provide multi-objective codon optimization functionality for synthetic gene design. COOL provides a simple and flexible interface for customizing codon optimization based on several design parameters such as individual codon usage, codon pairing, and codon adaptation index. User-defined sequences can also be compared against the COOL optimized ones to show the extent by which the user's sequences can be evaluated and further improved. The utility of COOL is demonstrated via a case study where the codon optimized sequence of an invertase enzyme is generated for the enhanced expression in E. coli.

  3. Use of estimated evolutionary strength at the codon level improves the prediction of disease-related protein mutations in humans.

    PubMed

    Capriotti, Emidio; Arbiza, Leonardo; Casadio, Rita; Dopazo, Joaquín; Dopazo, Hernán; Marti-Renom, Marc A

    2008-01-01

    Predicting the functional impact of protein variation is one of the most challenging problems in bioinformatics. A rapidly growing number of genome-scale studies provide large amounts of experimental data, allowing the application of rigorous statistical approaches for predicting whether a given single point mutation has an impact on human health. Up until now, existing methods have limited their source data to either protein or gene information. Novel in this work, we take advantage of both and focus on protein evolutionary information by using estimated selective pressures at the codon level. Here we introduce a new method (SeqProfCod) to predict the likelihood that a given protein variant is associated with human disease or not. Our method relies on a support vector machine (SVM) classifier trained using three sources of information: protein sequence, multiple protein sequence alignments, and the estimation of selective pressure at the codon level. SeqProfCod has been benchmarked with a large dataset of 8,987 single point mutations from 1,434 human proteins from SWISS-PROT. It achieves 82% overall accuracy and a correlation coefficient of 0.59, indicating that the estimation of the selective pressure helps in predicting the functional impact of single-point mutations. Moreover, this study demonstrates the synergic effect of combining two sources of information for predicting the functional effects of protein variants: protein sequence/profile-based information and the evolutionary estimation of the selective pressures at the codon level. The results of large-scale application of SeqProfCod over all annotated point mutations in SWISS-PROT (available for download at http://sgu.bioinfo.cipf.es/services/Omidios/; last accessed: 24 August 2007), could be used to support clinical studies.

  4. The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons

    PubMed Central

    Błażej, Paweł; Mackiewicz, Dorota; Wnętrzak, Małgorzata; Mackiewicz, Paweł

    2017-01-01

    There are two main forces that affect usage of synonymous codons: directional mutational pressure and selection. The effectiveness of protein translation is usually considered as the main selectional factor. However, biased codon usage can also be a byproduct of a general selection at the amino acid level interacting with nucleotide replacements. To evaluate the validity and strength of such an effect, we superimposed >3.5 billion unrestricted mutational processes on the selection of nonsynonymous substitutions based on the differences in physicochemical properties of the coded amino acids. Using a modified evolutionary optimization algorithm, we determined the conditions in which the effect on the relative codon usage is maximized. We found that the effect is enhanced by mutational processes generating more adenine and thymine than guanine and cytosine, as well as more purines than pyrimidines. Interestingly, this effect is observed only under an unrestricted model of nucleotide substitution, and disappears when the mutational process is time-reversible. Comparison of the simulation results with data for real protein coding sequences indicates that the impact of selection at the amino acid level on synonymous codon usage cannot be neglected. Furthermore, it can considerably interfere, especially in AT-rich genomes, with other selections on codon usage, e.g., translational efficiency. It may also lead to difficulties in the recognition of other effects influencing codon bias, and an overestimation of protein coding sequences whose codon usage is subjected to adaptational selection. PMID:28122952

  5. Nucleotide composition and codon usage bias of SRY gene.

    PubMed

    Choudhury, M N; Uddin, A; Chakraborty, S

    2017-01-26

    The SRY gene is present within the sex-determining region of the Y chromosome which is responsible for maleness in mammals. The nonuniform usage of synonymous codons in the mRNA transcript for encoding a particular amino acid is the codon usage bias (CUB). Analysis of codon usage pattern is important to understand the genetic and molecular organisation of a gene. It also helps in heterologous gene expression, design of primer and synthetic gene. However, the analysis of codon usage bias of SRY gene was not yet studied. We have used bioinformatic tools to analyse codon usage bias of SRY gene across mammals. Codon bias index (CBI) indicated that the overall extent of codon usage bias was weak. The relative synonymous codon usage (RSCU) analysis suggested that most frequently used codons had an A or C at the third codon position. Compositional constraint played an important role in codon usage pattern as evident from correspondence analysis (CA). Significant correlation among nucleotides constraints indicated that both mutation pressure and natural selection affect the codon usage pattern. Neutrality plot suggested that natural selection might play a major role, while mutation pressure might play a minor role in codon usage pattern in SRY gene in different species of mammals.

  6. A PCR-mutagenesis strategy for rapid detection of mutations in codon 634 of the ret proto-oncogene related to MEN 2A.

    PubMed Central

    Roqué, María; Pusiol, Eduardo; Perinetti, Héctor; Godoy, Clara Pott; Mayorga, Luis S

    2002-01-01

    Background Multiple endocrine neoplasias type 2A (MEN 2A) is a dominantly inherited cancer syndrome. Missence mutations in the codon encoding cysteine 634 of the ret proto-oncogene have been found in 85% of the MEN 2A families. The main tumour type always present in MEN 2A is medullar thyroid carcinoma (MTC). Only 25% of all MTC are hereditary, and generally they are identified by a careful family history. However, some familial MTCs are not easily detected by this means and underdiagnosis of MEN 2A is suspected. Methods DNA samples from MEN 2A patients were amplified by PCR. The products were incubated with the restriction enzyme Bst ApI or Bgl I. The samples were loaded in non-denaturing 10% Polyacrilamyde Gel and run at 120 volts for 40 min. The gels were stained with 10 μg/ml ethidium bromide, and the bands were visualized under a UV lamp. Results We developed a PCR-mutagenic method to check the integrity of the three bases of the cysteine 634 codon. Conclusion The method can be used to detect inherited mutations in MTC patients without a clear family history. The method is relatively simple to use as a routine test in these patients to decrease the underdiagnosis of MEN 2A. In addition, the assay can be used to screen affected families with any mutation in cysteine 634. PMID:12033991

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons

    PubMed Central

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

    2016-01-01

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

  10. Efficient expression of codon-adapted human acetaldehyde dehydrogenase 2 cDNA with 6xHis tag in Pichia pastoris.

    PubMed

    Zhao, YuFeng; Lei, MingKe; Wu, YuanXin; Zhang, ZiSheng; Wang, CunWen

    2009-10-01

    Human mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) catalyzes the oxidation of acetaldehyde to acetic acid. Therefore, ALDH2 has therapeutic potential in detoxification of acetaldehyde. Furthermore, ALDH2 catalyzes nitroglycerin to nitrate and 1, 2-glyceryldinitrate during therapy for angina pectoris, myocardial infarction, and heart failure. Large quantities of ALDH2 will be needed for potential clinical practice. In this study, Pichia pastoris was used as a platform for expression of human ALDH2. Based on the ALDH2*1 cDNA sequence, we designed ALDH2 cDNA by choosing the P. pastoris preferred codons and by decreasing the G + C content level. The sequence was synthesized using the overlap extension PCR method. The cDNA and 6xHis tags were subcloned into the plasmid pPIC9K. The recombinant protein was expressed in P. pastoris GS115 and purified using Ni(2+)-Sepharose affinity chromatography. The amount of secreted protein in the culture was 80 mg/L in shake-flask cultivation and 260 mg/L in high-density bioreactor fermentation. Secreted ALDH2 was easily purified from the culture supernatant by using Ni(2+)-Sepharose affinity chromatography. After purification of the fermentation supernatant, the enzyme had a specific activity of 1.2 U/mg protein. The yield was about 16 mg/L in a shake flask culture of P. pastoris GS115 which contained the original human ALDH2*1 cDNA.

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

    PubMed Central

    Dana, Alexandra; Tuller, Tamir

    2014-01-01

    The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons decoding time is a fundamental biomedical research question; however, due to a large number of variables affecting this process and the non-direct relation between them, a conclusive answer to this question has eluded so far researchers in the field. In this study, we perform a novel analysis of the ribosome profiling data of four organisms which enables ranking the decoding times of different codons while filtering translational phenomena such as experimental biases, extreme ribosomal pauses and ribosome traffic jams. Based on this filtering, we show for the first time that there is a significant correlation between tRNA concentrations and the codons estimated decoding time both in prokaryotes and in eukaryotes in natural conditions (−0.38 to −0.66, all P values <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

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

    PubMed

    Dana, Alexandra; Tuller, Tamir

    2014-08-01

    The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons decoding time is a fundamental biomedical research question; however, due to a large number of variables affecting this process and the non-direct relation between them, a conclusive answer to this question has eluded so far researchers in the field. In this study, we perform a novel analysis of the ribosome profiling data of four organisms which enables ranking the decoding times of different codons while filtering translational phenomena such as experimental biases, extreme ribosomal pauses and ribosome traffic jams. Based on this filtering, we show for the first time that there is a significant correlation between tRNA concentrations and the codons estimated decoding time both in prokaryotes and in eukaryotes in natural conditions (-0.38 to -0.66, all P values <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. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    PubMed

    Subramanian, Abhishek; Sarkar, Ram Rup

    2015-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Codon reassignment and amino acid composition in hemichordate mitochondria

    PubMed Central

    Castresana, Jose; Feldmaier-Fuchs, Gertraud; Pääbo, Svante

    1998-01-01

    In the mitochondrial genome of the hemichordate Balanoglossus carnosus, the codon AAA, which is assigned to lysine in most metazoans but to asparagine in echinoderms, is absent. Furthermore, the lysine tRNA gene carries an anticodon substitution that renders its gene product unable to decode AAA codons, whereas the asparagine tRNA gene has not changed to encode a tRNA with the ability to recognize AAA codons. Thus, the hemichordate mitochondrial genome can be regarded as an intermediate in the process of reassignment of mitochondrial AAA codons, where most metazoans represent the ancestral situation and the echinoderms the derived situation. This lends support to the codon capture hypothesis. We also show that the reassignment of the AAA codon is associated with a reduction in the relative abundance of lysine residues in mitochondrial proteins. PMID:9520430

  16. A generalized mechanistic codon model.

    PubMed

    Zaheri, Maryam; Dib, Linda; Salamin, Nicolas

    2014-09-01

    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. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Variation in global codon usage bias among prokaryotic organisms is associated with their lifestyles

    PubMed Central

    2011-01-01

    Background It is widely acknowledged that synonymous codons are used unevenly among genes in a genome. In organisms under translational selection, genes encoding highly expressed proteins are enriched with specific codons. This phenomenon, termed codon usage bias, is common to many organisms and has been recognized as influencing cellular fitness. This suggests that the global extent of codon usage bias of an organism might be associated with its phenotypic traits. Results To test this hypothesis we used a simple measure for assessing the extent of codon bias of an organism, and applied it to hundreds of sequenced prokaryotes. Our analysis revealed a large variability in this measure: there are organisms showing very high degrees of codon usage bias and organisms exhibiting almost no differential use of synonymous codons among different genes. Remarkably, we found that the extent of codon usage bias corresponds to the lifestyle of the organism. Especially, organisms able to live in a wide range of habitats exhibit high extents of codon usage bias, consistent with their need to adapt efficiently to different environments. Pathogenic prokaryotes also demonstrate higher extents of codon usage bias than non-pathogenic prokaryotes, in accord with the multiple environments that many pathogens occupy. Our results show that the previously observed correlation between growth rate and metabolic variability is attributed to their individual associations with codon usage bias. Conclusions Our results suggest that the extent of codon usage bias of an organism plays a role in the adaptation of prokaryotes to their environments. PMID:22032172

  18. In Arabidopsis thaliana codon volatility scores reflect GC3 composition rather than selective pressure

    PubMed Central

    2012-01-01

    Background Synonymous codon usage bias has typically been correlated with, and attributed to translational efficiency. However, there are other pressures on genomic sequence composition that can affect codon usage patterns such as mutational biases. This study provides an analysis of the codon usage patterns in Arabidopsis thaliana in relation to gene expression levels, codon volatility, mutational biases and selective pressures. Results We have performed synonymous codon usage and codon volatility analyses for all genes in the A. thaliana genome. In contrast to reports for species from other kingdoms, we find that neither codon usage nor volatility are correlated with selection pressure (as measured by dN/dS), nor with gene expression levels on a genome wide level. Our results show that codon volatility and usage are not synonymous, rather that they are correlated with the abundance of G and C at the third codon position (GC3). Conclusions Our results indicate that while the A. thaliana genome shows evidence for synonymous codon usage bias, this is not related to the expression levels of its constituent genes. Neither codon volatility nor codon usage are correlated with expression levels or selective pressures but, because they are directly related to the composition of G and C at the third codon position, they are the result of mutational bias. Therefore, in A. thaliana codon volatility and usage do not result from selection for translation efficiency or protein functional shift as measured by positive selection. PMID:22805311

  19. Synonymous codon usage patterns in different parasitic platyhelminth mitochondrial genomes.

    PubMed

    Chen, L; Yang, D Y; Liu, T F; Nong, X; Huang, X; Xie, Y; Fu, Y; Zheng, W P; Zhang, R H; Wu, X H; Gu, X B; Wang, S X; Peng, X R; Yang, G Y

    2013-02-27

    We analyzed synonymous codon usage patterns of the mitochondrial genomes of 43 parasitic platyhelminth species. The relative synonymous codon usage, the effective number of codons (NC) and the frequency of G+C at the third synonymously variable coding position were calculated. Correspondence analysis was used to determine the major variation trends shaping the codon usage patterns. Among the mitochondrial genomes of 19 trematode species, the GC content of third codon positions varied from 0.151 to 0.592, with a mean of 0.295 ± 0.116. In cestodes, the mean GC content of third codon positions was 0.254 ± 0.044. A comparison of the nucleotide composition at 4-fold synonymous sites revealed that, on average, there was a greater abundance of codons ending on U (51.9%) or A (22.7%) than on C (6.3%) or G (19.14%). Twenty-two codons, including UUU, UUA and UUG, were frequently used. In the NC-plot, most of points were distributed well below or around the expected NC curve. In addition to compositional constraints, the degree of hydrophobicity and the aromatic amino acids also influenced codon usage in the mitochondrial genomes of these 43 parasitic platyhelminth species.

  20. A new and updated resource for codon usage tables.

    PubMed

    Athey, John; Alexaki, Aikaterini; Osipova, Ekaterina; Rostovtsev, Alexandre; Santana-Quintero, Luis V; Katneni, Upendra; Simonyan, Vahan; Kimchi-Sarfaty, Chava

    2017-09-02

    Due to the degeneracy of the genetic code, most amino acids can be encoded by multiple synonymous codons. Synonymous codons naturally occur with different frequencies in different organisms. The choice of codons may affect protein expression, structure, and function. Recombinant gene technologies commonly take advantage of the former effect by implementing a technique termed codon optimization, in which codons are replaced with synonymous ones in order to increase protein expression. This technique relies on the accurate knowledge of codon usage frequencies. Accurately quantifying codon usage bias for different organisms is useful not only for codon optimization, but also for evolutionary and translation studies: phylogenetic relations of organisms, and host-pathogen co-evolution relationships, may be explored through their codon usage similarities. Furthermore, codon usage has been shown to affect protein structure and function through interfering with translation kinetics, and cotranslational protein folding. Despite the obvious need for accurate codon usage tables, currently available resources are either limited in scope, encompassing only organisms from specific domains of life, or greatly outdated. Taking advantage of the exponential growth of GenBank and the creation of NCBI's RefSeq database, we have developed a new database, the High-performance Integrated Virtual Environment-Codon Usage Tables (HIVE-CUTs), to present and analyse codon usage tables for every organism with publicly available sequencing data. Compared to existing databases, this new database is more comprehensive, addresses concerns that limited the accuracy of earlier databases, and provides several new functionalities, such as the ability to view and compare codon usage between individual organisms and across taxonomical clades, through graphical representation or through commonly used indices. In addition, it is being routinely updated to keep up with the continuous flow of new data in

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

    PubMed

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

    2017-06-01

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

  2. GRChombo: Numerical relativity with adaptive mesh refinement

    NASA Astrophysics Data System (ADS)

    Clough, Katy; Figueras, Pau; Finkel, Hal; Kunesch, Markus; Lim, Eugene A.; Tunyasuvunakool, Saran

    2015-12-01

    In this work, we introduce {\\mathtt{GRChombo}}: a new numerical relativity code which incorporates full adaptive mesh refinement (AMR) using block structured Berger-Rigoutsos grid generation. The code supports non-trivial ‘many-boxes-in-many-boxes’ mesh hierarchies and massive parallelism through the message passing interface. {\\mathtt{GRChombo}} evolves the Einstein equation using the standard BSSN formalism, with an option to turn on CCZ4 constraint damping if required. The AMR capability permits the study of a range of new physics which has previously been computationally infeasible in a full 3 + 1 setting, while also significantly simplifying the process of setting up the mesh for these problems. We show that {\\mathtt{GRChombo}} can stably and accurately evolve standard spacetimes such as binary black hole mergers and scalar collapses into black holes, demonstrate the performance characteristics of our code, and discuss various physics problems which stand to benefit from the AMR technique.

  3. GRChombo : Numerical Relativity with Adaptive Mesh Refinement

    SciTech Connect

    Clough, Katy; Figueras, Pau; Finkel, Hal; Kunesch, Markus; Lim, Eugene A.; Tunyasuvunakool, Saran

    2015-12-24

    In this work, we introduce GRChombo: a new numerical relativity code which incorporates full adaptive mesh refinement (AMR) using block structured Berger-Rigoutsos grid generation. The code supports non-trivial 'many-boxes-in-many-boxes' mesh hierarchies and massive parallelism through the message passing interface. GRChombo evolves the Einstein equation using the standard BSSN formalism, with an option to turn on CCZ4 constraint damping if required. The AMR capability permits the study of a range of new physics which has previously been computationally infeasible in a full 3 + 1 setting, while also significantly simplifying the process of setting up the mesh for these problems. We show that GRChombo can stably and accurately evolve standard spacetimes such as binary black hole mergers and scalar collapses into black holes, demonstrate the performance characteristics of our code, and discuss various physics problems which stand to benefit from the AMR technique.

  4. Adaptive management of watersheds and related resources

    USGS Publications Warehouse

    Williams, Byron K.

    2009-01-01

    The concept of learning about natural resources through the practice of management has been around for several decades and by now is associated with the term adaptive management. The objectives of this paper are to offer a framework for adaptive management that includes an operational definition, a description of conditions in which it can be usefully applied, and a systematic approach to its application. Adaptive decisionmaking is described as iterative, learning-based management in two phases, each with its own mechanisms for feedback and adaptation. The linkages between traditional experimental science and adaptive management are discussed.

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

    PubMed Central

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

    2016-01-01

    Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts. PMID:26927064

  6. Looking into the genome of Thermosynechococcus elongatus (thermophilic cyanobacteria) with codon selection and usage perspective.

    PubMed

    Prabha, Ratna; Singh, Dhananjaya P; Rai, Anil

    2015-01-01

    Genome analysis of thermophilic cyanobacterium, Thermosynechococcus elongatus BP-1 revealed factors ruling choices of codons in this organism. Multiple parameters like Nc, GC3s, RSCU, Codon Adaptation Index (CAI), optimal and rare codons, codon-pair context and amino acid usage were analysed and compositional constraint was identified as major factor. Wide range of Nc values for the same GC3 content suggested the role of translational selection. Mutational bias is suggested at synonymous position. Among optimal codons for translation, most were GC-ending. Seven codons (AGA, AGG, AUA, UAA, UAG, UCA and UGA) were found to have least occurrence in the entire genome and except stop codons all were A-ending (exception AGG). Most widely used codon-pair in the genome are G-ending or C-ending and A-ending or U-ending codons make pair with G-ending or C-ending codons. Amino acids which are largely distributed in T. elongatus tend to use G-ending or C-ending codons most frequently. Findings showed cumulative role of translational selection, translational accuracy and gene expression levels with mutational bias as key player in codon selection pattern of this organism.

  7. Codon catalog usage and the genome hypothesis.

    PubMed Central

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

    1980-01-01

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

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

    PubMed

    Martín-Galiano, Antonio J; Wells, Jerry M; de la Campa, Adela G

    2004-07-01

    A codon-profile strategy was used to predict gene expression levels in Streptococcus pneumoniae. Predicted highly expressed (PHE) genes included those encoding glycolytic and fermentative enzymes, sugar-conversion systems and carbohydrate-transporters. Additionally, some genes required for infection that are involved in oxidative metabolism and hydrogen peroxide production were PHE. Low expression values were predicted for genes encoding specific regulatory proteins like two-component systems and competence genes. Correspondence analysis localized 484 ORFs which shared a distinctive codon profile in the right horn. These genes had a mean G+C content (33.4 %) that was lower than the bulk of the genome coding sequences (39.7 %), suggesting that many of them were acquired by horizontal transfer. Half of these genes (242) were pseudogenes, ORFs shorter than 80 codons or without assigned function. The remaining genes included several virulence factors, such as capsular genes, iga, lytB, nanB, pspA, choline-binding proteins, and functions related to DNA acquisition, such as restriction-modification systems and comDE. In order to compare predicted translation rate with the relative amounts of mRNA for each gene, the codon adaptation index (CAI) values were compared with microarray fluorescence intensity values following hybridization of labelled RNA from laboratory-grown cultures. High mRNA amounts were observed in 32.5 % of PHE genes and in 64 % of the 25 genes with the highest CAI values. However, high relative amounts of RNA were also detected in 10.4 % of non-PHE genes, such as those encoding fatty acid metabolism enzymes and proteases, suggesting that their expression might also be regulated at the level of transcription or mRNA stability under the conditions tested. The effects of codon bias and mRNA amount on different gene groups in S. pneumoniae are discussed.

  9. Measurements of translation initiation from all 64 codons in E. coli

    PubMed Central

    Hecht, Ariel; Glasgow, Jeff; Bawazer, Lukmaan A.; Munson, Matthew S.; Cochran, Jennifer R.

    2017-01-01

    Abstract Our understanding of translation underpins our capacity to engineer living systems. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are considered as the ‘start codons’ for translation initiation in Escherichia coli. Translation is typically not thought to initiate from the 61 remaining codons. Here, we quantified translation initiation of green fluorescent protein and nanoluciferase in E. coli from all 64 triplet codons and across a range of DNA copy number. We detected initiation of protein synthesis above measurement background for 47 codons. Translation from non-canonical start codons ranged from 0.007 to 3% relative to translation from AUG. Translation from 17 non-AUG codons exceeded the highest reported rates of non-cognate codon recognition. Translation initiation from non-canonical start codons may contribute to the synthesis of peptides in both natural and synthetic biological systems. PMID:28334756

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

    DTIC Science & Technology

    2016-09-20

    alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons...codes. codon choice | genome editing | recoded genomes The genetic code possesses inherent redundancy (1), with up tosix different codons specifying a...strong preference for certain codons over synonymous alternatives (5, 6). Although different species have evolved to prefer different codons, codon

  11. The identities of stop codon reassignments support ancestral tRNA stop codon decoding activity as a facilitator of gene duplication and evolution of novel function.

    PubMed

    Massey, Steven E

    2017-03-27

    Stop codon reassignments are widely distributed in prokaryotic, eukaryotic and organellar genomes, but are remarkably convergent in terms of the stop codons and amino acids reassigned. Strikingly, the identities of stop codon reassignments are closely matched to the properties of naturally occurring nonsense suppressor (NONS) tRNAs, suggesting that pre-existing nonsense suppression in an ancestral tRNA facilitated the occurrence of stop codon reassignments. Here this idea is expanded, by exploring the mechanism by which the gene duplication of tRNAs has occurred, leading to the reassignment of stop codons. Two types of stop codon reassignment are identified: those that necessitate a tRNA gene duplication, and those that do not because a single tRNA can recognize the reassigned stop codon and the canonical codon(s) for the cognate amino acid. Where tRNA gene duplication has occurred, this implies a multi-functional ancestral NONS tRNA, followed by adaptive mutation in the anticodon of one of the gene duplicates to become complementary to the stop codon, constituting a clear example of escape from adaptive conflict. The best exemplar is the UAA+UAG - >gln reassignment, which has occurred 9 times independently in a diverse range of genomes, and appears to reflect the widespread occurrence of naturally occurring nonsense suppression of the UAA+UAG stop codons by glutamine tRNAs. Consideration of pre-existing tRNA functionality and the mechanism of gene duplication provide new insights into the process of stop codon reassignment.

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

    PubMed Central

    2011-01-01

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

  13. Comparative characterization analysis of synonymous codon usage bias in classical swine fever virus.

    PubMed

    Xu, Xin; Fei, Dongliang; Han, Huansheng; Liu, Honggui; Zhang, Jiayong; Zhou, Yulong; Xu, Chuang; Wang, Hongbin; Cao, Hongwei; Zhang, Hua

    2017-06-01

    Classical swine fever virus (CSFV) is responsible for the highly contagious viral disease of swine, and causes great economic loss in the swine-raising industry. Considering the significance of CSFV, a systemic analysis was performed to study its codon usage patterns. In this study, using the complete genome sequences of 76 CSFV representing three genotypes, we firstly analyzed the relative nucleotide composition, effective number of codon (ENC) and synonymous codon usage in CSFV genomes. The results showed that CSFV is GC-moderate genome and the third-ended codons are not preferentially used. Every ENC values in CSFV genomes are >50, indicating that the codon usage bias is comparatively slight. Subsequently, we performed the correspondence analysis (COA) to investigate synonymous codon usage variation among all of the CSFV genomes. We found that codon usage bias in these CSFV genomes is greatly influenced by G + C mutation, which suggests that mutational pressure may be the main factor determining the codon usage biases. Moreover, most of the codon usage bias among different CSFV ORFs is directly related to the nucleotide composition. Other factors, such as hydrophobicity and aromaticity, also influence the codon usage variation among CSFV genomes. Our study represents the most comprehensive analysis of codon usage patterns in CSFV genome and provides a basic understanding of the mechanisms for its codon usage bias. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Transcriptome Analysis of Core Dinoflagellates Reveals a Universal Bias towards “GC” Rich Codons

    PubMed Central

    Williams, Ernest; Place, Allen; Bachvaroff, Tsvetan

    2017-01-01

    Although dinoflagellates are a potential source of pharmaceuticals and natural products, the mechanisms for regulating and producing these compounds are largely unknown because of extensive post-transcriptional control of gene expression. One well-documented mechanism for controlling gene expression during translation is codon bias, whereby specific codons slow or even terminate protein synthesis. Approximately 10,000 annotatable genes from fifteen “core” dinoflagellate transcriptomes along a range of overall guanine and cytosine (GC) content were used for codonW analysis to determine the relative synonymous codon usage (RSCU) and the GC content at each codon position. GC bias in the analyzed dataset and at the third codon position varied from 51% and 54% to 66% and 88%, respectively. Codons poor in GC were observed to be universally absent, but bias was most pronounced for codons ending in uracil followed by adenine (UA). GC bias at the third codon position was able to explain low abundance codons as well as the low effective number of codons. Thus, we propose that a bias towards codons rich in GC bases is a universal feature of core dinoflagellates, possibly relating to their unique chromosome structure, and not likely a major mechanism for controlling gene expression. PMID:28448468

  15. Trends in the codon usage patterns of Chromohalobacter salexigens genes

    PubMed Central

    Sanjukta, Rajkumari; Farooqi, Mohammad Samir; Sharma, Naveen; Rai, Anil; Mishra, Dwijesh Chandra; Singh, Dhananjaya P

    2012-01-01

    Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage (RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein also influence the codon usage variation of genes to some extent. A comparison of the relative synonymous codon usage between 10% each of highly and lowly expressed genes determines 23 optimal codons, which are statistically over represented in the former group of genes and may provide useful information for salt-stressed gene prediction and gene-transformation. Furthermore, genes for regulatory functions; mobile and extrachromosomal element functions; and cell envelope are observed to be highly expressed. The study could provide insight into the gene expression response of halophilic bacteria and facilitate establishment of effective strategies to develop salt-tolerant crops of agronomic value. PMID:23251043

  16. Homozygosity for premature stop codon of the MHC class I chain-related gene A (MIC-A) is associated with early activation of islet autoimmunity of DR3/4-DQ2/8 high risk DAISY relatives.

    PubMed

    Ide, Akane; Babu, Sunanda R; Robles, David T; Wang, Tianbao; Erlich, Henry A; Bugawan, Teodorica L; Rewers, Marian; Fain, Pamela R; Eisenbarth, George S

    2005-07-01

    We hypothesized that homozygosity for the major histocompatibility complex (MHC) class I chain-related gene A (MIC-A)5.1 allele with premature stop codon would increase diabetes risk of individuals followed from infancy in the DAISY study (Diabetes Autoimmunity Study in the young). Forty five percent (10/22) of relatives (siblings and offspring cohort, SOC) who developed anti-islet autoantibodies were MIC-A5.1/5.1 homozygous. Of SOC individuals without autoantibodies, 12/58 (19%, p = 0.02) were MIC-A5.1 homozygous. By life table analysis of expression of autoantibodies, DR3-DQ2/ DR4-DQ8 more than 50% of MIC-A5.1 homozygous children became autoantibody positive by 7 years of age, compared to delayed development of autoantibodies for non-MIC-A5.1/5.1 DR3-DQ2/ DR4-DQ8 children (p = 0.005). For DR3-DQ2/DR4-DQ8 nonrelatives, the risk of activating anti-islet autoimmunity remained low even with MIC-A5.1 homozygosity suggesting that there are additional factors contributing to the marked risk of relatives compared to the general population with the DR3-DQ2/DR4-DQ8 genotype.

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

    PubMed Central

    Moore, Gregory L.; Maranas, Costas D.

    2002-01-01

    We present a systematic computational framework, eCodonOpt, for designing parental DNA sequences for directed evolution experiments through codon usage optimization. Given a set of homologous parental proteins to be recombined at the DNA level, the optimal DNA sequences encoding these proteins are sought for a given diversity objective. We find that the free energy of annealing between the recombining DNA sequences is a much better descriptor of the extent of crossover formation than sequence identity. Three different diversity targets are investigated for the DNA shuffling protocol to showcase the utility of the eCodonOpt framework: (i) maximizing the average number of crossovers per recombined sequence; (ii) minimizing bias in family DNA shuffling so that each of the parental sequence pair contributes a similar number of crossovers to the library; and (iii) maximizing the relative frequency of crossovers in specific structural regions. Each one of these design challenges is formulated as a constrained optimization problem that utilizes 0–1 binary variables as on/off switches to model the selection of different codon choices for each residue position. Computational results suggest that many-fold improvements in the crossover frequency, location and specificity are possible, providing valuable insights for the engineering of directed evolution protocols. PMID:12034828

  18. Human Alpha and Beta Papillomaviruses Use Different Synonymous Codon Profiles

    PubMed Central

    Cladel, Nancy M.; Bertotto, Alex; Christensen, Neil D.

    2013-01-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field. PMID:20157772

  19. Human alpha and beta papillomaviruses use different synonymous codon profiles.

    PubMed

    Cladel, Nancy M; Bertotto, Alex; Christensen, Neil D

    2010-06-01

    Human papillomaviruses use rare codons relative to their hosts. It has been theorized that this is a mechanism to allow the virus to escape immune surveillance. In the present study, we examined the codings of four major genes of 21 human alpha (mucosatropic) viruses and 16 human beta (cutaneous-tropic) viruses. We compared the codon usage of different genes from a given papillomavirus and also the same genes from different papillomaviruses. Our data showed that codon usage was not always uniform between two genes of a given papillomavirus or between the same genes of papillomaviruses from different genera. We speculate as to why this might be and conclude that codon usage in the papillomaviruses may not only play a role in facilitating escape from immune surveillance but may also underlie some of the unanswered questions in the papillomavirus field.

  20. The evolution of codon usage in structural and non-structural viral genes: the case of Avian coronavirus and its natural host Gallus gallus.

    PubMed

    Brandão, Paulo Eduardo

    2013-12-26

    To assess the codon evolution in virus-host systems, Avian coronavirus and its natural host Gallus gallus were used as a model. Codon usage (CU) was measured for the viral spike (S), nucleocapsid (N), nonstructural protein 2 (NSP2) and papain-like protease (PL(pro)) genes from a diverse set of A. coronavirus lineages and for G. gallus genes (lung surfactant protein A, intestinal cholecystokinin, oviduct ovomucin alpha subunit, kidney vitamin D receptor and the ubiquitary beta-actin) for different A. coronavirus replicating sites. Relative synonymous codon usage (RSCU) trees accommodating all virus and host genes in a single topology showed a higher proximity of A. coronavirus CU to the respiratory tract for all genes. The codon adaptation index (CAI) showed a lower adaptation of S to G. gallus compared to NSP2, PL(pro) and N. The effective number of codons (Nc) and GC3% revealed that natural selection and genetic drift are the evolutionary forces driving the codon usage evolution of both A. coronavirus and G. gallus regardless of the gene being considered. The spike gene showed only one 100% conserved amino acid position coded by an A. coronavirus preferred codon, a significantly low number when compared to the three other genes (p<0.0001). Virus CU evolves independently for each gene in a manner predicted by the protein function, with a balance between natural selection and mutation pressure, giving further molecular basis for the viruses' ability to exploit the host's cellular environment in a concerted virus-host molecular evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Divergence in codon usage of Lactobacillus species.

    PubMed Central

    Pouwels, P H; Leunissen, J A

    1994-01-01

    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

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

    PubMed

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

    2010-08-01

    In this study, we calculated the relative synonymous codon usage (RSCU) values and codon usage bias (CUB) values to implement a comparative analysis of codon usage pattern of open reading frames (ORFs) which belong to the two main genotypes of porcine reproductive and respiratory syndrome virus (PRRSV). By analysis of synonymous codon usage values in each ORF of PRRSV, the optimal codons for most amino acids were all C or G-ended codons except GAU for Asp, CAU for His, UUU for Phe and CCU for Pro. The synonymous codon usage patterns in different ORFs of PRRSV were different and genetically conserved. Among them, ORF1a, ORF4, ORF5 and ORF7 could cluster these strains into the two main serotypes (EU and US). Due to mutational pressure, compositional constraint played an important role in shaping the synonymous codon usage pattern in different ORFs, and the synonymous codon usage diversity in ORFs was correlated with gene function. The degree of CUB for some particular amino acids under strong selection pressure probably served as a potential genetic marker for each ORF in PRRSV. However, gene length and translational selection in nature had no effect on the synonymous codon usage pattern in PRRSV. These conclusions could not only offer an insight into the synonymous codon usage pattern and differentiation of gene function, but also assist in understanding the discrepancy of evolution among ORFs in PRRSV. Copyright 2010 Elsevier B.V. All rights reserved.

  3. Age-related forgetting in locomotor adaptation.

    PubMed

    Malone, Laura A; Bastian, Amy J

    2016-02-01

    The healthy aging process affects the ability to learn and remember new facts and tasks. Prior work has shown that motor learning can be adversely affected by non-motor deficits, such as time. Here we investigated how age, and a dual task influence the learning and forgetting of a new walking pattern. We studied healthy younger (<30 yo) and older adults (>50 yo) as they alternated between 5-min bouts of split-belt treadmill walking and resting. Older subjects learned a new walking pattern at the same rate as younger subjects, but forgot some of the new pattern during the rest breaks. We tested if forgetting was due to reliance on a cognitive strategy that was not fully engaged after rest breaks. When older subjects performed a dual cognitive task to reduce strategic control of split-belt walking, their adaptation rate slowed, but they still forgot much of the new pattern during the rest breaks. Our results demonstrate that the healthy aging process is one component that weakens motor memories during rest breaks and that this phenomenon cannot be explained solely by reliance on a conscious strategy in older adults.

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

    PubMed

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

    2013-04-01

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

  5. Properties and determinants of codon decoding time distributions

    PubMed Central

    2014-01-01

    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. PMID:25572668

  6. Synonymous codon usage influences the local protein structure observed

    PubMed Central

    Saunders, Rhodri; Deane, Charlotte M.

    2010-01-01

    Translation of mRNA into protein is a unidirectional information flow process. Analysing the input (mRNA) and output (protein) of translation, we find that local protein structure information is encoded in the mRNA nucleotide sequence. The Coding Sequence and Structure (CSandS) database developed in this work provides a detailed mapping between over 4000 solved protein structures and their mRNA. CSandS facilitates a comprehensive analysis of codon usage over many organisms. In assigning translation speed, we find that relative codon usage is less informative than tRNA concentration. For all speed measures, no evidence was found that domain boundaries are enriched with slow codons. In fact, genes seemingly avoid slow codons around structurally defined domain boundaries. Translation speed, however, does decrease at the transition into secondary structure. Codons are identified that have structural preferences significantly different from the amino acid they encode. However, each organism has its own set of ‘significant codons’. Our results support the premise that codons encode more information than merely amino acids and give insight into the role of translation in protein folding. PMID:20530529

  7. Principles of start codon recognition in eukaryotic translation initiation

    PubMed Central

    Lind, Christoffer; Åqvist, Johan

    2016-01-01

    Selection of the correct start codon during initiation of translation on the ribosome is a key event in protein synthesis. In eukaryotic initiation, several factors have to function in concert to ensure that the initiator tRNA finds the cognate AUG start codon during mRNA scanning. The two initiation factors eIF1 and eIF1A are known to provide important functions for the initiation process and codon selection. Here, we have used molecular dynamics free energy calculations to evaluate the energetics of initiator tRNA binding to different near-cognate codons on the yeast 40S ribosomal subunit, in the presence and absence of these two initiation factors. The results show that eIF1 and eIF1A together cause a relatively uniform and high discrimination against near-cognate codons. This works such that eIF1 boosts the discrimination against a first position near-cognate G-U mismatch, and also against a second position A-A base pair, while eIF1A mainly acts on third codon position. The computer simulations further reveal the structural basis of the increased discriminatory effect caused by binding of eIF1 and eIF1A to the 40S ribosomal subunit. PMID:27280974

  8. Measure of synonymous codon usage diversity among genes in bacteria.

    PubMed

    Suzuki, Haruo; Saito, Rintaro; Tomita, Masaru

    2009-06-01

    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. 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. 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.

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

    PubMed

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

    2016-09-02

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

  10. Mutation Bias is the Driving Force of Codon Usage in the Gallus gallus genome

    PubMed Central

    Rao, Yousheng; Wu, Guozuo; Wang, Zhangfeng; Chai, Xuewen; Nie, Qinghua; Zhang, Xiquan

    2011-01-01

    Synonymous codons are used with different frequencies both among species and among genes within the same genome and are controlled by neutral processes (such as mutation and drift) as well as by selection. Up to now, a systematic examination of the codon usage for the chicken genome has not been performed. Here, we carried out a whole genome analysis of the chicken genome by the use of the relative synonymous codon usage (RSCU) method and identified 11 putative optimal codons, all of them ending with uracil (U), which is significantly departing from the pattern observed in other eukaryotes. Optimal codons in the chicken genome are most likely the ones corresponding to highly expressed transfer RNA (tRNAs) or tRNA gene copy numbers in the cell. Codon bias, measured as the frequency of optimal codons (Fop), is negatively correlated with the G + C content, recombination rate, but positively correlated with gene expression, protein length, gene length and intron length. The positive correlation between codon bias and protein, gene and intron length is quite different from other multi-cellular organism, as this trend has been only found in unicellular organisms. Our data displayed that regional G + C content explains a large proportion of the variance of codon bias in chicken. Stepwise selection model analyses indicate that G + C content of coding sequence is the most important factor for codon bias. It appears that variation in the G + C content of CDSs accounts for over 60% of the variation of codon bias. This study suggests that both mutation bias and selection contribute to codon bias. However, mutation bias is the driving force of the codon usage in the Gallus gallus genome. Our data also provide evidence that the negative correlation between codon bias and recombination rates in G. gallus is determined mostly by recombination-dependent mutational patterns. PMID:22039174

  11. CodonO: codon usage bias analysis within and across genomes

    PubMed Central

    Angellotti, Michael C.; Bhuiyan, Shafquat B.; Chen, Guorong; Wan, Xiu-Feng

    2007-01-01

    Synonymous codon usage biases are associated with various biological factors, such as gene expression level, gene length, gene translation initiation signal, protein amino acid composition, protein structure, tRNA abundance, mutation frequency and patterns, and GC compositions. Quantification of codon usage bias helps understand evolution of living organisms. A codon usage bias pipeline is demanding for codon usage bias analyses within and across genomes. Here we present a CodonO webserver service as a user-friendly tool for codon usage bias analyses across and within genomes in real time. The webserver is available at http//www.sysbiology.org/CodonO. Contact: wanhenry@yahoo.com. PMID:17537810

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

    PubMed Central

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

    2014-01-01

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

  13. Convergent local adaptation to climate in distantly related conifers.

    PubMed

    Yeaman, Sam; Hodgins, Kathryn A; Lotterhos, Katie E; Suren, Haktan; Nadeau, Simon; Degner, Jon C; Nurkowski, Kristin A; Smets, Pia; Wang, Tongli; Gray, Laura K; Liepe, Katharina J; Hamann, Andreas; Holliday, Jason A; Whitlock, Michael C; Rieseberg, Loren H; Aitken, Sally N

    2016-09-23

    When confronted with an adaptive challenge, such as extreme temperature, closely related species frequently evolve similar phenotypes using the same genes. Although such repeated evolution is thought to be less likely in highly polygenic traits and distantly related species, this has not been tested at the genome scale. We performed a population genomic study of convergent local adaptation among two distantly related species, lodgepole pine and interior spruce. We identified a suite of 47 genes, enriched for duplicated genes, with variants associated with spatial variation in temperature or cold hardiness in both species, providing evidence of convergent local adaptation despite 140 million years of separate evolution. These results show that adaptation to climate can be genetically constrained, with certain key genes playing nonredundant roles.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

    Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID:27278133

  16. Visual-Haptic Adaptation Is Determined by Relative Reliability

    PubMed Central

    Burge, Johannes; Girshick, Ahna R.; Banks, Martin S.

    2011-01-01

    Accurate calibration of sensory estimators is critical for maintaining accurate estimates of the environment. Classically, it was assumed that sensory calibration occurs by one sense changing to become consistent with vision; this is visual dominance. Recently, it has been proposed that changes in estimators occur according to their relative reliabilities; this is the reliability-based model. We show that if cue combination occurs according to relative reliability, then reliability-based calibration assures minimum-variance sensory estimates over time. Recent studies are qualitatively consistent with the reliability-based model, but none have shown that the predictions are quantitatively accurate. We conducted an experiment in which the model could be assessed quantitatively. Subjects indicated whether visual, haptic, and visual–haptic planar surfaces appeared slanted positively or negatively from frontoparallel. In preadaptation, we determined the visual and haptic slants of perceived frontoparallel, and measured visual and haptic reliabilities. We varied visual reliability by adjusting the size of the viewable stimulus. Haptic reliability was fixed. During adaptation, subjects were exposed to visual–haptic surfaces with a discrepancy between the visual and haptic slants. After adaptation, we remeasured the visual and haptic slants of perceived frontoparallel. When vision was more reliable, haptics adapted to match vision. When vision was less reliable, vision adapted to match haptics. Most importantly, the ratio of visual and haptic adaptation was quantitatively predicted by relative reliability. The amount of adaptation of one sensory estimator relative to another depends strongly on the relative reliabilities of the two estimators. PMID:20519546

  17. Codon usage analysis of photolyase encoding genes of cyanobacteria inhabiting diverse habitats.

    PubMed

    Rajneesh; Pathak, Jainendra; Kannaujiya, Vinod K; Singh, Shailendra P; Sinha, Rajeshwar P

    2017-07-01

    Nucleotide and amino acid compositions were studied to determine the genomic and structural relationship of photolyase gene in freshwater, marine and hot spring cyanobacteria. Among three habitats, photolyase encoding genes from hot spring cyanobacteria were found to have highest GC content. The genomic GC content was found to influence the codon usage and amino acid variability in photolyases. The third position of codon was found to have more effect on amino acid variability in photolyases than the first and second positions of codon. The variation of amino acids Ala, Asp, Glu, Gly, His, Leu, Pro, Gln, Arg and Val in photolyases of three different habitats was found to be controlled by first position of codon (G1C1). However, second position (G2C2) of codon regulates variation of Ala, Cys, Gly, Pro, Arg, Ser, Thr and Tyr contents in photolyases. Third position (G3C3) of codon controls incorporation of amino acids such as Ala, Phe, Gly, Leu, Gln, Pro, Arg, Ser, Thr and Tyr in photolyases from three habitats. Photolyase encoding genes of hot spring cyanobacteria have 85% codons with G or C at third position, whereas marine and freshwater cyanobacteria showed 82 and 60% codons, respectively, with G or C at third position. Principal component analysis (PCA) showed that GC content has a profound effect in separating the genes along the first major axis according to their RSCU (relative synonymous codon usage) values, and neutrality analysis indicated that mutational pressure has resulted in codon bias in photolyase genes of cyanobacteria.

  18. Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats

    PubMed Central

    Wolf, Andrew S.; Grayhack, Elizabeth J.

    2015-01-01

    Quality control systems monitor and stop translation at some ribosomal stalls, but it is unknown if halting translation at such stalls actually prevents synthesis of abnormal polypeptides. In yeast, ribosome stalling occurs at Arg CGA codon repeats, with even two consecutive CGA codons able to reduce translation by up to 50%. The conserved eukaryotic Asc1 protein limits translation through internal Arg CGA codon repeats. We show that, in the absence of Asc1 protein, ribosomes continue translating at CGA codons, but undergo substantial frameshifting with dramatically higher levels of frameshifting occurring with additional repeats of CGA codons. Frameshifting depends upon the slow or inefficient decoding of these codons, since frameshifting is suppressed by increased expression of the native tRNAArg(ICG) that decodes CGA codons by wobble decoding. Moreover, the extent of frameshifting is modulated by the position of the CGA codon repeat relative to the translation start site. Thus, translation fidelity depends upon Asc1-mediated quality control. PMID:25792604

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

    PubMed

    Castells, Matías; Victoria, Matías; Colina, Rodney; Musto, Héctor; Cristina, Juan

    2017-06-17

    Bovine coronavirus (BCoV) belong to the genus Betacoronavirus of the family Coronaviridae. BCoV are widespread around the world and cause enteric or respiratory infections among cattle, leading to important economic losses to the beef and dairy industry worldwide. To study the relation of codon usage among viruses and their hosts is essential to understand host-pathogen interaction, evasion from host's immune system and evolution. We performed a comprehensive analysis of codon usage and composition of BCoV. The global codon usage among BCoV strains is similar. Significant differences of codon preferences in BCoV genes in relation to codon usage of Bos taurus host genes were found. Most of the highly frequent codons are U-ending. G + C compositional constraint and dinucleotide composition also plays a role in the overall pattern of BCoV codon usage. The results of these studies revealed that mutational bias is a leading force shaping codon usage in this virus. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern.

  20. Analysis of codon usage patterns in Ginkgo biloba reveals codon usage tendency from A/U-ending to G/C-ending

    PubMed Central

    He, Bing; Dong, Hui; Jiang, Cong; Cao, Fuliang; Tao, Shentong; Xu, Li-an

    2016-01-01

    As one of the most ancient tree species, the codon usage pattern analysis of Ginkgo biloba is a useful way to understand its evolutionary and genetic mechanisms. Several studies have been conducted on angiosperms, but seldom on gymnosperms. Based on RNA-Seq data of the G. biloba transcriptome, amount to 17,579 unigenes longer than 300 bp were selected and analyzed from 68,547 candidates. The codon usage pattern tended towards more frequently use of A/U-ending codons, which showed an obvious gradient progressing from gymnosperms to dicots to monocots. Meanwhile, analysis of high/low-expression unigenes revealed that high-expression unigenes tended to use G/C-ending codons together with more codon usage bias. Variation of unigenes with different functions suggested that unigenes involving in environment adaptation use G/C-ending codons more frequently with more usage bias, and these results were consistent with the conclusion that the formation of G. biloba codon usage bias was dominated by natural selection. PMID:27808241

  1. Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review

    PubMed Central

    2014-01-01

    Background KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. Methods We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse’s Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. Results KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence

  2. Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.

    PubMed

    Imamura, Yu; Lochhead, Paul; Yamauchi, Mai; Kuchiba, Aya; Qian, Zhi Rong; Liao, Xiaoyun; Nishihara, Reiko; Jung, Seungyoun; Wu, Kana; Nosho, Katsuhiko; Wang, Yaoyu E; Peng, Shouyong; Bass, Adam J; Haigis, Kevin M; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Ogino, Shuji

    2014-05-31

    KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse's Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for

  3. Initiation of translation at AUC, AUA and AUU codons in Escherichia coli.

    PubMed

    Romero, A; García, P

    1991-12-01

    A truncated form of the HBL murein hydrolase, encoded by the temperate bacteriophage HB-3, was cloned in a pUC-derivative and translated in Escherichia coli using AUC as start codon, as confirmed by biochemical, immunological, and N-terminal analyses. Using site-directed mutagenesis, we have changed this AUC codon into AUA, AUU and AUG codons. The relative translation efficiencies for these triplets were about 5% for AUC and AUU and 7.5% for AUA compared to that of AUG codon. In the same gene arrangement E. coli beta-galactosidase was also translated at moderate efficiency using AUC as initiator.

  4. Codon Preference Optimization Increases Prokaryotic Cystatin C Expression

    PubMed Central

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

    2012-01-01

    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

  5. Role of premature stop codons in bacterial evolution.

    PubMed

    Wong, Tit-Yee; Fernandes, Sanjit; Sankhon, Naby; Leong, Patrick P; Kuo, Jimmy; Liu, Jong-Kang

    2008-10-01

    When the stop codons TGA, TAA, and TAG are found in the second and third reading frames of a protein-encoding gene, they are considered premature stop codons (PSC). Deinococcus radiodurans disproportionately favored TGA more than the other two triplets as a PSC. The TGA triplet was also found more often in noncoding regions and as a stop codon, though the bias was less pronounced. We investigated this phenomenon in 72 bacterial species with widely differing chromosomal GC contents. Although TGA and TAG were compositionally similar, we found a great variation in use of TGA but a very limited range of use of TAG. The frequency of use of TGA in the gene sequences generally increased with the GC content of the chromosome, while the frequency of use of TAG, like that of TAA, was inversely proportional to the GC content of the chromosome. The patterns of use of TAA, TGA and TAG as real stop codons were less biased and less influenced by the GC content of the chromosome. Bacteria with higher chromosomal GC contents often contained fewer PSC trimers in their genes. Phylogenetically related bacteria often exhibited similar PSC ratios. In addition, metabolically versatile bacteria have significantly fewer PSC trimers in their genes. The bias toward TGA but against TAG as a PSC could not be explained either by the preferential usage of specific codons or by the GC contents of individual chromosomes. We proposed that the quantity and the quality of the PSC in the genome might be important in bacterial evolution.

  6. Balanced Codon Usage Optimizes Eukaryotic Translational Efficiency

    PubMed Central

    Qian, Wenfeng; Yang, Jian-Rong; Pearson, Nathaniel M.; Maclean, Calum; Zhang, Jianzhi

    2012-01-01

    Cellular efficiency in protein translation is an important fitness determinant in rapidly growing organisms. It is widely believed that synonymous codons are translated with unequal speeds and that translational efficiency is maximized by the exclusive use of rapidly translated codons. Here we estimate the in vivo translational speeds of all sense codons from the budding yeast Saccharomyces cerevisiae. Surprisingly, preferentially used codons are not translated faster than unpreferred ones. We hypothesize that this phenomenon is a result of codon usage in proportion to cognate tRNA concentrations, the optimal strategy in enhancing translational efficiency under tRNA shortage. Our predicted codon–tRNA balance is indeed observed from all model eukaryotes examined, and its impact on translational efficiency is further validated experimentally. Our study reveals a previously unsuspected mechanism by which unequal codon usage increases translational efficiency, demonstrates widespread natural selection for translational efficiency, and offers new strategies to improve synthetic biology. PMID:22479199

  7. Analysis of synonymous codon usage in Zika virus.

    PubMed

    Hussain, Snawar; Rasool, Sahibzada Tasleem

    2017-09-01

    Zika virus is a zoonotic pathogen, which have made frequent incursion into the human population in Africa and South East Asia over the course of several decades but never reached to the pandemic proportions until the most recent outbreak. Viruses are solely dependent on host synthetic machinery for their replication cycle; therefore, replication and persistence in a host species of different genetic background requires certain degree of adaptation. These adaptations are necessary to avoid detection from host immune surveillance and maximize the utilization of available resources for efficient viral replication. Study of genomic composition and codon usage pattern not only offer an insight into the adaptation of viruses to their new host, but may also provide some information about pathogenesis and spread of the virus. To elucidate the genetic features and synonymous codon usage bias in ZIKV genome, a comprehensive analysis was performed on 80 full-length ZIKV sequences. Our analyses shows that the overall extent of codon usage bias in ZIKV genome is low and affected by nucleotide composition, protein properties, natural selection, and gene expression level. Copyright © 2017. Published by Elsevier B.V.

  8. Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum.

    PubMed

    Heaphy, Stephen M; Mariotti, Marco; Gladyshev, Vadim N; Atkins, John F; Baranov, Pavel V

    2016-11-01

    mRNA translation in many ciliates utilizes variant genetic codes where stop codons are reassigned to specify amino acids. To characterize the repertoire of ciliate genetic codes, we analyzed ciliate transcriptomes from marine environments. Using codon substitution frequencies in ciliate protein-coding genes and their orthologs, we inferred the genetic codes of 24 ciliate species. Nine did not match genetic code tables currently assigned by NCBI. Surprisingly, we identified a novel genetic code where all three standard stop codons (TAA, TAG, and TGA) specify amino acids in Condylostoma magnum We provide evidence suggesting that the functions of these codons in C. magnum depend on their location within mRNA. They are decoded as amino acids at internal positions, but specify translation termination when in close proximity to an mRNA 3' end. The frequency of stop codons in protein coding sequences of closely related Climacostomum virens suggests that it may represent a transitory state. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Site-specific codon bias in bacteria

    SciTech Connect

    Smith, J.M.; Smith, N.H.

    1996-03-01

    Sequences of the gapA and ompA genes from 10 genera of enterobacteria have been analyzed. There is strong bias in codon usage, but different synonymous codons are preferred at different sites in the same gene. Site-specific preference for unfavored codons is not confined to the first 100 codons and is usually manifest between two codons utilizing the same tRNA. Statistical analyses, based on conclusions reached in an accompanying paper, show that the use of an unfavored codon at a given site in different genera is not due to common descent and must therefore be caused either by sequence-specific mutation or sequence-specific selection. Reasons are given for thinking that sequence-specific mutation cannot be responsible. We are unable to explain the preference between synonymous codons ending in C or T, but synonymous choice between A and G at third sites is largely explained by avoidance of AG-G (where the hyphen indicates the boundary between codons). We also observed that the preferred codon for proline in Enterobacter cloacea has changed from CCG to CCA. 27 refs., 7 tabs.

  10. Synonymous codon usage in TTSuV2: analysis and comparison with TTSuV1.

    PubMed

    Zhang, Zhicheng; Dai, Wei; Dai, Dingzhen

    2013-01-01

    Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years. In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically conserved. Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position. Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes. A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1. However the similarity was low for each virus and its host. These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes.

  11. Exploring codon context bias for synthetic gene design of a thermostable invertase in Escherichia coli.

    PubMed

    Pek, Han Bin; Klement, Maximilian; Ang, Kok Siong; Chung, Bevan Kai-Sheng; Ow, Dave Siak-Wei; Lee, Dong-Yup

    2015-01-01

    Various isoforms of invertases from prokaryotes, fungi, and higher plants has been expressed in Escherichia coli, and codon optimisation is a widely-adopted strategy for improvement of heterologous enzyme expression. Successful synthetic gene design for recombinant protein expression can be done by matching its translational elongation rate against heterologous host organisms via codon optimization. Amongst the various design parameters considered for the gene synthesis, codon context bias has been relatively overlooked compared to individual codon usage which is commonly adopted in most of codon optimization tools. In addition, matching the rates of transcription and translation based on secondary structure may lead to enhanced protein folding. In this study, we evaluated codon context fitness as design criterion for improving the expression of thermostable invertase from Thermotoga maritima in Escherichia coli and explored the relevance of secondary structure regions for folding and expression. We designed three coding sequences by using (1) a commercial vendor optimized gene algorithm, (2) codon context for the whole gene, and (3) codon context based on the secondary structure regions. Then, the codon optimized sequences were transformed and expressed in E. coli. From the resultant enzyme activities and protein yield data, codon context fitness proved to have the highest activity as compared to the wild-type control and other criteria while secondary structure-based strategy is comparable to the control. Codon context bias was shown to be a relevant parameter for enhancing enzyme production in Escherichia coli by codon optimization. Thus, we can effectively design synthetic genes within heterologous host organisms using this criterion.

  12. Preschooler Sleep Patterns Related to Cognitive and Adaptive Functioning

    ERIC Educational Resources Information Center

    Keefe-Cooperman, Kathleen; Brady-Amoon, Peggy

    2014-01-01

    Research Findings: Preschoolers' sleep patterns were examined related to cognitive and adaptive functioning. The sample consisted of 874 typically developing preschool children with a mean age of 40.01 months. Parent/caregiver reports of children's sleep pattern factors, Stanford-Binet 5 intelligence scale scores, and Behavior Assessment System…

  13. Preschooler Sleep Patterns Related to Cognitive and Adaptive Functioning

    ERIC Educational Resources Information Center

    Keefe-Cooperman, Kathleen; Brady-Amoon, Peggy

    2014-01-01

    Research Findings: Preschoolers' sleep patterns were examined related to cognitive and adaptive functioning. The sample consisted of 874 typically developing preschool children with a mean age of 40.01 months. Parent/caregiver reports of children's sleep pattern factors, Stanford-Binet 5 intelligence scale scores, and Behavior Assessment System…

  14. Adaptation of Panic-Related Psychopathology Measures to Russian

    ERIC Educational Resources Information Center

    Kotov, Roman; Schmidt, Norman B.; Zvolensky, Michael J.; Vinogradov, Alexander; Antipova, Anna V.

    2005-01-01

    The study reports results of adaptation of panic-related psychopathology measures to Russian, including the Anxiety Sensitivity Index (ASI), the Agoraphobic Cognitions Questionnaire (ACQ), and the Mobility Inventory for Agoraphobia (MIA). Psychometric properties (e.g., reliability, factor structure, endorsement) and external validity of the…

  15. Research in adaptive management: working relations and the research process.

    Treesearch

    Amanda C. Graham; Linda E. Kruger

    2002-01-01

    This report analyzes how a small group of Forest Service scientists participating in efforts to implement adaptive management approach working relations, and how they understand and apply the research process. Nine scientists completed a questionnaire to assess their preferred mode of thinking (the Herrmann Brain Dominance Instrument), engaged in a facilitated...

  16. Inflammatory bowel disease related innate immunity and adaptive immunity.

    PubMed

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD.

  17. Individual and age-related variation in chromatic contrast adaptation

    PubMed Central

    Elliott, Sarah L.; Werner, John S.; Webster, Michael A.

    2012-01-01

    Precortical color channels are tuned primarily to the LvsM (stimulation of L and M cones varied, but S cone stimulation held constant) or SvsLM (stimulation of S cones varied, but L and M cone stimulation held constant) cone-opponent (cardinal) axes, but appear elaborated in the cortex to form higher-order mechanisms tuned to both cardinal and intermediate directions. One source of evidence for these higher-order mechanisms has been the selectivity of color contrast adaptation for noncardinal directions, yet the degree of this selectivity has varied widely across the small sample of observers tested in previous studies. This study explored the possible bases for this variation, and in particular tested whether it reflected age-related changes in the distribution or tuning of color mechanisms. Observers included 15 younger (18–22 years of age) and 15 older individuals (66–82), who adapted to temporal modulations along one of four chromatic axes (two cardinal and two intermediate axes) and then matched the hue and contrast of test stimuli lying along eight different directions in the equiluminant plane. All observers exhibited aftereffects that were selective for both the cardinal and intermediate directions, although selectivity was weaker for the intermediate axes. The degree of selectivity increased with the magnitude of adaptation for all axes, and thus adaptation strength alone may account for much of the variance in selectivity among observers. Older observers showed a stronger magnitude of adaptation thus, surprisingly, more conspicuous evidence for higher-order mechanisms. For both age groups the aftereffects were well predicted by response changes in chromatic channels with linear spectral sensitivities, and there was no evidence for weakened channel tuning with aging. The results suggest that higher-order mechanisms may become more exposed in observers or conditions in which the strength of adaptation is greater, and that both chromatic contrast

  18. Adaptation.

    PubMed

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  19. Adaptive evolution of the osmoregulation-related genes in cetaceans during secondary aquatic adaptation.

    PubMed

    Xu, Shixia; Yang, Yunxia; Zhou, Xuming; Xu, Junxiao; Zhou, Kaiya; Yang, Guang

    2013-09-09

    Osmoregulation was a primary challenge for cetaceans during the evolutionary transition from a terrestrial to a mainly hyperosmotic environment. Several physiological mechanisms have been suggested to maintain the water and salt balance in cetaceans, but their genetic and evolutionary bases remain poorly explored. The current study investigated the genes involved in osmoregulation in cetaceans and compared them with their counterparts in terrestrial mammals to test whether adaptive evolution occurred during secondary aquatic adaptation. The present study analyzed the molecular evolution of 11 osmoregulation-related genes in 11 cetacean species, which represented all of the major cetacean clades. The results demonstrated positive selection acting on angiotensin converting enzyme (ACE), angiotensinogen (AGT), SLC14A2, and aquaporin 2 (AQP2). This evidence for the positive selection of AQP2 and SLC14A2 suggests that the adaptive evolution of these genes has helped to enhance the capacity for water and urea transport, thereby leading to the concentration of urine, which is an efficient mechanism for maintaining the water balance. By contrast, a series of positively selected amino acid residues identified in the ACE and AGT (two key members of the renin-angiotensin-aldosterone system, RAAS) proteins of cetaceans suggests that RAAS might have been adapted to maintain the water and salt balance in response to a hyperosmotic environment. Radical amino acid changes in positively selected sites were distributed among most internal and terminal branches of the cetacean phylogeny, which suggests the pervasively adaptive evolution of osmoregulation since the origin of cetaceans and their subsequent diversification. This is the first comprehensive analysis of the molecular evolution of osmoregulation-related genes in cetaceans in response to selection pressure from a generally hyperosmotic environment. Four genes, i.e., AQP2, SLC14A2, ACE, and AGT were subject to positive

  20. Evolution of codon usage in Zika virus genomes is host and vector specific

    PubMed Central

    Butt, Azeem Mehmood; Nasrullah, Izza; Qamar, Raheel; Tong, Yigang

    2016-01-01

    The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors. PMID:27729643

  1. Evolution of codon usage in Zika virus genomes is host and vector specific.

    PubMed

    Butt, Azeem Mehmood; Nasrullah, Izza; Qamar, Raheel; Tong, Yigang

    2016-10-12

    The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.

  2. Minigene-like inhibition of protein synthesis mediated by hungry codons near the start codon

    PubMed Central

    Jacinto-Loeza, Eva; Vivanco-Domínguez, Serafín; Guarneros, Gabriel; Hernández-Sánchez, Javier

    2008-01-01

    Rare AGA or AGG codons close to the initiation codon inhibit protein synthesis by a tRNA-sequestering mechanism as toxic minigenes do. To further understand this mechanism, a parallel analysis of protein synthesis and peptidyl-tRNA accumulation was performed using both a set of lacZ constructs where AGAAGA codons were moved codon by codon from +2, +3 up to +7, +8 positions and a series of 3–8 codon minigenes containing AGAAGA codons before the stop codon. β-Galactosidase synthesis from the AGAAGA lacZ constructs (in a Pth defective in vitro system without exogenous tRNA) diminished as the AGAAGA codons were closer to AUG codon. Likewise, β-galactosidase expression from the reporter +7 AGA lacZ gene (plus tRNA, 0.25 μg/μl) waned as the AGAAGAUAA minigene shortened. Pth counteracted both the length-dependent minigene effect on the expression of β-galactosidase from the +7 AGA lacZ reporter gene and the positional effect from the AGAAGA lacZ constructs. The +2, +3 AGAAGA lacZ construct and the shortest +2, +3 AGAAGAUAA minigene accumulated the highest percentage of peptidyl-tRNAArg4. These observations lead us to propose that hungry codons at early positions, albeit with less strength, inhibit protein synthesis by a minigene-like mechanism involving accumulation of peptidyl-tRNA. PMID:18583364

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  4. [Adaptation of a questionnaire measuring representations related to work disability].

    PubMed

    Albert, V; Coutu, M-F; Durand, M-J

    2013-06-01

    Health, illness and treatment representations have been described as key factors for return to work. The Revised Illness Perception Questionnaire (IPQ-R) is a quantitative tool available to assess these factors. However, an adaptation is necessary before its use with workers on prolonged work disability presenting musculoskeletal disorders (MSD). Two distinct phases were carried out, firstly, by adapting the IPQ-R for a population of workers in prolonged work disability related to an MSD and, secondly, by conducting a pre-test on the adapted questionnaire to assess item clarity. PHASE 1: The Technique for Research of Information by the Animation of a Group of Experts (TRIAGE) was selected to proceed with the adaptation. TRIAGE is an inductive and structured method aiming at the attainment of group consensus. Consensus was obtained in two steps: for the individual production, each expert had to judge the pertinence of the questioned elements and suggested new elements if needed; for the group production, all suggestions submitted were sorted according to TRIAGE systematic procedure, in order to retain the most pertinent ones by group consensus. Analysis was done simultaneously to data collection, by the attainment of group consensus. The group of experts consisted of six clinicians and two researchers. For the clinicians, selection criteria consisted of: being an occupational therapist or a psychologist and working for at least 2 years in a vocational rehabilitation setting for workers in prolonged work disability; for the researchers, being affiliated to a university and to have pursued a least one research project regarding prolonged work disability following MSD and development/validation of assessment tools. As a result of the adaptation process eight items were excluded because they were not considered pertinent by the experts. The label "illness" was changed for "current health condition" and 26 new items have been added to the questionnaire to better account

  5. Universal response-adaptation relation in bacterial chemotaxis.

    PubMed

    Krembel, Anna K; Neumann, Silke; Sourjik, Victor

    2015-01-01

    The bacterial strategy of chemotaxis relies on temporal comparisons of chemical concentrations, where the probability of maintaining the current direction of swimming is modulated by changes in stimulation experienced during the recent past. A short-term memory required for such comparisons is provided by the adaptation system, which operates through the activity-dependent methylation of chemotaxis receptors. Previous theoretical studies have suggested that efficient navigation in gradients requires a well-defined adaptation rate, because the memory time scale needs to match the duration of straight runs made by bacteria. Here we demonstrate that the chemotaxis pathway of Escherichia coli does indeed exhibit a universal relation between the response magnitude and adaptation time which does not depend on the type of chemical ligand. Our results suggest that this alignment of adaptation rates for different ligands is achieved through cooperative interactions among chemoreceptors rather than through fine-tuning of methylation rates for individual receptors. This observation illustrates a yet-unrecognized function of receptor clustering in bacterial chemotaxis.

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

    PubMed Central

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

    2016-01-01

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

  7. Evolutionary switches between two serine codon sets are driven by selection

    PubMed Central

    Rogozin, Igor B.; Belinky, Frida; Pavlenko, Vladimir; Shabalina, Svetlana A.; Kristensen, David M.; Koonin, Eugene V.

    2016-01-01

    Serine is the only amino acid that is encoded by two disjoint codon sets so that a tandem substitution of two nucleotides is required to switch between the two sets. Previously published evidence suggests that, for the most evolutionarily conserved serines, the codon set switch occurs by simultaneous substitution of two nucleotides. Here we report a genome-wide reconstruction of the evolution of serine codons in triplets of closely related species from diverse prokaryotes and eukaryotes. The results indicate that the great majority of codon set switches proceed by two consecutive nucleotide substitutions, via a threonine or cysteine intermediate, and are driven by selection. These findings imply a strong pressure of purifying selection in protein evolution, which in the case of serine codon set switches occurs via an initial deleterious substitution quickly followed by a second, compensatory substitution. The result is frequent reversal of amino acid replacements and, at short evolutionary distances, pervasive homoplasy. PMID:27799560

  8. Timing is everything: unifying codon translation rates and nascent proteome behavior.

    PubMed

    Nissley, Daniel A; O'Brien, Edward P

    2014-12-31

    Experiments have demonstrated that changing the rate at which the ribosome translates a codon position in an mRNA molecule's open reading frame can alter the behavior of the newly synthesized protein. That is, codon translation rates can govern nascent proteome behavior. We emphasize that this phenomenon is a manifestation of the nonequilibrium nature of cotranslational processes, and as such, there exist theoretical tools that offer a potential means to quantitatively predict the influence of codon translation rates on the broad spectrum of nascent protein behaviors including cotranslational folding, aggregation, and translocation. We provide a review of the experimental evidence for the impact that codon translation rates can have, followed by a discussion of theoretical methods that can describe this phenomenon. The development and application of these tools are likely to provide fundamental insights into protein maturation and homeostasis, codon usage bias in organisms, the origins of translation related diseases, and new rational design methods for biotechnology and biopharmaceutical applications.

  9. An entropy-based technique for classifying bacterial chromosomes according to synonymous codon usage.

    PubMed

    Hart, Andrew; Martínez, Servet

    2017-06-01

    We present a framework based on information theoretic concepts and the Dirichlet distribution for classifying chromosomes based on the degree to which they use synonymous codons uniformly or preferentially, that is, whether or not codons that code for an amino acid appear with the same relative frequency. At its core is a measure of codon usage bias we call the Kullback-Leibler codon information bias (KL-CIB or CIB for short). Being defined in terms of conditional entropy makes KL-CIB an ideal and natural quantity for expressing a chromosome's degree of departure from uniform synonymous codon usage. Applying the approach to a large collection of annotated bacterial chromosomes reveals three distinct groups of bacteria.

  10. Codon Constraints on Closed 2D Shapes,

    DTIC Science & Technology

    2014-09-26

    19843$ CODON CONSTRAINTS ON CLOSED 2D SHAPES Go Whitman Richards "I Donald D. Hoffman’ D T 18 Abstract: Codons are simple primitives for describing plane...RSONAL AUT"ORtIS) Richards, Whitman & Hoffman, Donald D. 13&. TYPE OF REPORT 13b. TIME COVERED N/A P8 AT F RRrT t~r. Ago..D,) is, PlE COUNT Reprint...outlines, if figure and ground are ignored. Later, we will address the problem of indexing identical codon descriptors that have different figure

  11. Universality and Shannon entropy of codon usage

    NASA Astrophysics Data System (ADS)

    Frappat, L.; Minichini, C.; Sciarrino, A.; Sorba, P.

    2003-12-01

    The distribution functions of codon usage probabilities, computed over all the available GenBank data for 40 eukaryotic biological species and five chloroplasts, are best fitted by the sum of a constant, an exponential, and a linear function in the rank of usage. For mitochondria the analysis is not conclusive. These functions are characterized by parameters that strongly depend on the total guanine and cytosine (GC) content of the coding regions of biological species. It is predicted that the codon usage is the same in all exonic genes with the same GC content. The Shannon entropy for codons, also strongly dependent on the exonic GC content, is computed.

  12. Translation efficiencies of synonymous codons are not always correlated with codon usage in tobacco chloroplasts.

    PubMed

    Nakamura, Masayuki; Sugiura, Masahiro

    2007-01-01

    Codon usage in chloroplasts is different from that in prokaryotic and eukaryotic nuclear genomes. However, no experimental approach has been made to analyse the translation efficiency of individual codons in chloroplasts. We devised an in vitro assay for translation efficiencies using synthetic mRNAs, and measured the translation efficiencies of five synonymous codon groups in tobacco chloroplasts. Among four alanine codons (GCN, where N is U, C, A or G), GCU was the most efficient for translation, whereas the chloroplast genome lacks tRNA genes corresponding to GCU. Phenylalanine and tyrosine are each encoded by two codons (UUU/C and UAU/C, respectively). Phenylalanine UUC and tyrosine UAC were translated more than twice as efficiently than UUU and UAU, respectively, contrary to their codon usage, whereas translation efficiencies of synonymous codons for alanine, aspartic acid and asparagine were parallel to their codon usage. These observations indicate that translation efficiencies of individual codons are not always correlated with codon usage in vitro in chloroplasts. This raises an important issue for foreign gene expression in chloroplasts.

  13. Dietary nitrogen alters codon bias and genome composition in parasitic microorganisms.

    PubMed

    Seward, Emily A; Kelly, Steven

    2016-11-15

    Genomes are composed of long strings of nucleotide monomers (A, C, G and T) that are either scavenged from the organism's environment or built from metabolic precursors. The biosynthesis of each nucleotide differs in atomic requirements with different nucleotides requiring different quantities of nitrogen atoms. However, the impact of the relative availability of dietary nitrogen on genome composition and codon bias is poorly understood. Here we show that differential nitrogen availability, due to differences in environment and dietary inputs, is a major determinant of genome nucleotide composition and synonymous codon use in both bacterial and eukaryotic microorganisms. Specifically, low nitrogen availability species use nucleotides that require fewer nitrogen atoms to encode the same genes compared to high nitrogen availability species. Furthermore, we provide a novel selection-mutation framework for the evaluation of the impact of metabolism on gene sequence evolution and show that it is possible to predict the metabolic inputs of related organisms from an analysis of the raw nucleotide sequence of their genes. Taken together, these results reveal a previously hidden relationship between cellular metabolism and genome evolution and provide new insight into how genome sequence evolution can be influenced by adaptation to different diets and environments.

  14. Standard Codon Substitution Models Overestimate Purifying Selection for Nonstationary Data

    PubMed Central

    Yap, Von Bing; Huttley, Gavin A.

    2017-01-01

    Estimation of natural selection on protein-coding sequences is a key comparative genomics approach for de novo prediction of lineage-specific adaptations. Selective pressure is measured on a per-gene basis by comparing the rate of nonsynonymous substitutions to the rate of synonymous substitutions. All published codon substitution models have been time-reversible and thus assume that sequence composition does not change over time. We previously demonstrated that if time-reversible DNA substitution models are applied in the presence of changing sequence composition, the number of substitutions is systematically biased towards overestimation. We extend these findings to the case of codon substitution models and further demonstrate that the ratio of nonsynonymous to synonymous rates of substitution tends to be underestimated over three data sets of mammals, vertebrates, and insects. Our basis for comparison is a nonstationary codon substitution model that allows sequence composition to change. Goodness-of-fit results demonstrate that our new model tends to fit the data better. Direct measurement of nonstationarity shows that bias in estimates of natural selection and genetic distance increases with the degree of violation of the stationarity assumption. Additionally, inferences drawn under time-reversible models are systematically affected by compositional divergence. As genomic sequences accumulate at an accelerating rate, the importance of accurate de novo estimation of natural selection increases. Our results establish that our new model provides a more robust perspective on this fundamental quantity. PMID:28175284

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

    PubMed Central

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

    2014-01-01

    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

  16. Evolutionary Dynamics of Abundant Stop Codon Readthrough

    PubMed Central

    Jungreis, Irwin; Kellis, Manolis

    2016-01-01

    Translational stop codon readthrough emerged as a major regulatory mechanism affecting hundreds of genes in animal genomes, based on recent comparative genomics and ribosomal profiling evidence, but its evolutionary properties remain unknown. Here, we leverage comparative genomic evidence across 21 Anopheles mosquitoes to systematically annotate readthrough genes in the malaria vector Anopheles gambiae, and to provide the first study of abundant readthrough evolution, by comparison with 20 Drosophila species. Using improved comparative genomics methods for detecting readthrough, we identify evolutionary signatures of conserved, functional readthrough of 353 stop codons in the malaria vector, Anopheles gambiae, and of 51 additional Drosophila melanogaster stop codons, including several cases of double and triple readthrough and of readthrough of two adjacent stop codons. We find that most differences between the readthrough repertoires of the two species arose from readthrough gain or loss in existing genes, rather than birth of new genes or gene death; that readthrough-associated RNA structures are sometimes gained or lost while readthrough persists; that readthrough is more likely to be lost at TAA and TAG stop codons; and that readthrough is under continued purifying evolutionary selection in mosquito, based on population genetic evidence. We also determine readthrough-associated gene properties that predate readthrough, and identify differences in the characteristic properties of readthrough genes between clades. We estimate more than 600 functional readthrough stop codons in mosquito and 900 in fruit fly, provide evidence of readthrough control of peroxisomal targeting, and refine the phylogenetic extent of abundant readthrough as following divergence from centipede. PMID:27604222

  17. Comparative genome sequence analysis of Sulfolobus acidocaldarius and 9 other isolates of its genus for factors influencing codon and amino acid usage.

    PubMed

    Nayak, Kinshuk Chandra

    2013-01-15

    In the present study, major constraints for codon and amino acid usage of Sulfolobus acidocaldarius, Sulfolobus solfataricus, Sulfolobus tokodali, Sulfolobus islandis and 6 other isolates from islandicus species of genus Sulfolobus were investigated. Correspondence analysis revealed high significant correlation between the major trend of synonymous codon usage and gene expression level, as assessed by the "Codon Adaptation Index" (CAI). There is a significant negative correlation between Nc (Effective number of codons) and CAI demonstrating role of codon bias as an important determinant of codon usage. The significant correlation between major trend of synonymous codon usage and GC3s (G+C at third synonymous position) indicated dominant role of mutational bias in codon usage pattern. The result was further supported from SCUO (synonymous codon usage order) analysis. The amino acid usage was found to be significantly influenced by aromaticity and hydrophobicity of proteins. However, translational selection which causes a preference for codons that are most rapidly translated by current tRNA with multiple copy numbers was not found to be highly dominating for all studied isolates. Notably, 26 codons that were found to be optimally used by genes of S. acidocaldarius at higher expression level and its comparative analysis with 9 other isolates may provide some useful clues for further in vivo genetic studies on this genus.

  18. Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases.

    PubMed Central

    Stenico, M; Lloyd, A T; Sharp, P M

    1994-01-01

    Synonymous codon usage varies considerably among Caenorhabditis elegans genes. Multivariate statistical analyses reveal a single major trend among genes. At one end of the trend lie genes with relatively unbiased codon usage. These genes appear to be lowly expressed, and their patterns of codon usage are consistent with mutational biases influenced by the neighbouring nucleotide. At the other extreme lie genes with extremely biased codon usage. These genes appear to be highly expressed, and their codon usage seems to have been shaped by selection favouring a limited number of translationally optimal codons. Thus, the frequency of these optimal codons in a gene appears to be correlated with the level of gene expression, and may be a useful indicator in the case of genes (or open reading frames) whose expression levels (or even function) are unknown. A second, relatively minor trend among genes is correlated with the frequency of G at synonymously variable sites. It is not yet clear whether this trend reflects variation in base composition (or mutational biases) among regions of the C.elegans genome, or some other factor. Sequence divergence between C.elegans and C.briggsae has also been studied. PMID:8041603

  19. Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli

    PubMed Central

    Napolitano, Michael G.; Landon, Matthieu; Gregg, Christopher J.; Lajoie, Marc J.; Govindarajan, Lakshmi; Mosberg, Joshua A.; Kuznetsov, Gleb; Goodman, Daniel B.; Vargas-Rodriguez, Oscar; Isaacs, Farren J.; Söll, Dieter; Church, George M.

    2016-01-01

    The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 “recalcitrant” AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional “safe replacement zone” (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes. PMID:27601680

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    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.

  1. tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

    PubMed Central

    Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

    2016-01-01

    Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria—which models tuberculous granulomas—are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria. PMID:27834374

  2. tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

    NASA Astrophysics Data System (ADS)

    Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

    2016-11-01

    Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria--which models tuberculous granulomas--are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.

  3. Autophagy is an adaptive response in desmin-related cardiomyopathy

    PubMed Central

    Tannous, Paul; Zhu, Hongxin; Johnstone, Janet L.; Shelton, John M.; Rajasekaran, Namakkal S.; Benjamin, Ivor J.; Nguyen, Lan; Gerard, Robert D.; Levine, Beth; Rothermel, Beverly A.; Hill, Joseph A.

    2008-01-01

    A missense mutation in the αB-crystallin (CryAB) gene triggers a severe form of desmin-related cardiomyopathy (DRCM) characterized by accumulation of misfolded proteins. We hypothesized that autophagy increases in response to protein aggregates and that this autophagic activity is adaptive. Mutant CryAB (CryABR120G) triggered a >2-fold increase in cardiomyocyte autophagic activity, and blunting autophagy increased the rate of aggregate accumulation and the abundance of insoluble CryABR120G-associated aggregates. Cardiomyocyte-restricted overexpression of CryABR120G in mice induced intracellular aggregate accumulation and systolic heart failure by 12 months. As early as 2 months (well before the earliest declines in cardiac function), we detected robust autophagic activity. To test the functional significance of autophagic activation, we crossed CryABR120G mice with animals harboring heterozygous inactivation of beclin 1, a gene required for autophagy. Blunting autophagy in vivo dramatically hastened heart failure progression with a 3-fold increase in interstitial fibrosis, greater accumulation of polyubiquitinated proteins, larger and more extensive intracellular aggregates, accelerated ventricular dysfunction, and early mortality. This study reports activation of autophagy in DRCM. Further, our findings point to autophagy as an adaptive response in this proteotoxic form of heart disease. PMID:18621691

  4. Childhood Depression: Relation to Adaptive, Clinical and Predictor Variables

    PubMed Central

    Garaigordobil, Maite; Bernarás, Elena; Jaureguizar, Joana; Machimbarrena, Juan M.

    2017-01-01

    The study had two goals: (1) to explore the relations between self-assessed childhood depression and other adaptive and clinical variables (2) to identify predictor variables of childhood depression. Participants were 420 students aged 7–10 years old (53.3% boys, 46.7% girls). Results revealed: (1) positive correlations between depression and clinical maladjustment, school maladjustment, emotional symptoms, internalizing and externalizing problems, problem behaviors, emotional reactivity, and childhood stress; and (2) negative correlations between depression and personal adaptation, global self-concept, social skills, and resilience (sense of competence and affiliation). Linear regression analysis including the global dimensions revealed 4 predictors of childhood depression that explained 50.6% of the variance: high clinical maladjustment, low global self-concept, high level of stress, and poor social skills. However, upon introducing the sub-dimensions, 9 predictor variables emerged that explained 56.4% of the variance: many internalizing problems, low family self-concept, high anxiety, low responsibility, low personal self-assessment, high social stress, few aggressive behaviors toward peers, many health/psychosomatic problems, and external locus of control. The discussion addresses the importance of implementing prevention programs for childhood depression at early ages. PMID:28572787

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

    PubMed Central

    2009-01-01

    Background Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes. Results We assign an evolutionary age to a gene based on the relative positions of its identified homologues in a standard phylogenetic tree. This yields a classification of all genes in a genome to several evolutionary age classes. The present study starts from the observation that each age class of genes has a unique codon usage and proceeds to provide a quantitative analysis of the codon usage in these classes. This observation is made for the genomes of Homo sapiens, Mus musculus, and Drosophila melanogaster. It is even more remarkable that the differences between codon usages in different age groups exhibit similar and consistent behavior in various organisms. While we find that GC content and gene length are also associated with the evolutionary age of genes, they can provide only a partial explanation for the observed codon usage. Conclusion While factors such as GC content, mutational bias, and selection shape the codon usage in a genome, the evolutionary history of an organism over hundreds of millions of years is an overlooked property that is strongly linked to GC content, protein length, and, even more significantly, to the codon usage of metazoan genomes. PMID:19995431

  6. The usage of codons which are similar to stop codons in the genomes of Xylella fastidiosa and Xanthomonas citri.

    PubMed

    Galves-dos-Santos, Dilermando P; Martins-de-Souza, Daniel

    2011-03-01

    During the evolution of living organisms, a natural selection event occurs toward the optimization of their genomes regarding the usage of codons. During this process which is known as codon bias, a set of preferred codons is naturally defined in the genome of a given organism, since there are 61 possible codons (plus 3 stop codons) to 20 amino acids. Such event leads to optimization of metabolic cellular processes such as translational efficiency, RNA stability and energy saving. Although we know why, we do not know how exactly a set of preferred codons for each amino acid is defined for a given genome considering that the usage frequency of each synonymous codons is peculiar to each organism. In order to help answering this question, we analyzed the usage frequency of codons which are similar to stop codons, since a minor mutation on these codons may lead to a stop codon into the open reading frame compromising the protein expression as a result. We found a reduced use of those codons in Xanthomomas axonopodis pv. citri which presents an optimized genome regarding codon usage. On the other hand, such codons are more often used in Xylella fastidiosa, which does not seem to have established codon preferences as previously shown. Our results support that a set of preferred codons is not randomly selected and propose new ideas to the field warranting further experiments in this regard.

  7. Computerized Adaptive Testing of Music-Related Skills.

    ERIC Educational Resources Information Center

    Vispoel, Walter P.; Coffman, Don D.

    1992-01-01

    Reports the findings of a study of university marching band members' tonal memory skills and their preferences between adaptive and paper-and-pencil testing. Concludes that adaptive testing yielded greater reliability and validity scores. Indicates that students preferred adaptive tests over paper-and-pencil music tests. (SG)

  8. Analysis of synonymous codon usage in Aeropyrum pernix K1 and other Crenarchaeota microorganisms.

    PubMed

    Jiang, Peng; Sun, Xiao; Lu, Zuhong

    2007-03-01

    In this study, a comparative analysis of the codon usage bias was performed in Aeropyrum pernix K1 and two other phylogenetically related Crenarchaeota microorganisms (i.e., Pyrobaculum aerophilum str. IM2 and Sulfolobus acidocaldarius DSM 639). The results indicated that the synonymous codon usage in A. pernix K1 was less biased, which was highly correlated with the GC(3S) value. The codon usage patterns were phylogenetically conserved among these Crenarchaeota microorganisms. Comparatively, it is the species function rather than the gene function that determines their gene codon usage patterns. A. pernix K1, P. aerophilum str. IM2, and S. acidocaldarius DSM 639 live in differently extreme conditions. It is presumed that the living environment played an important role in determining the codon usage pattern of these microorganisms. Besides, there was no strain-specific codon usage among these microorganisms. The extent of codon bias in A. pernix K1 and S. acidocaldarius DSM 639 were highly correlated with the gene expression level, but no such association was detected in P. aerophilum str. IM2 genomes.

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

    PubMed Central

    Liu, Jibin; Zhu, Dekang; Ma, Guangpeng; Liu, Mafeng; Wang, Mingshu; Jia, Renyong; Chen, Shun; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Riemerella anatipestifer (RA) belongs to the Flavobacteriaceae family and can cause a septicemia disease in poultry. The synonymous codon usage patterns of bacteria reflect a series of evolutionary changes that enable bacteria to improve tolerance of the various environments. We detailed the codon usage patterns of RA isolates from the available 12 sequenced genomes by multiple codon and statistical analysis. Nucleotide compositions and relative synonymous codon usage (RSCU) analysis revealed that A or U ending codons are predominant in RA. Neutrality analysis found no significant correlation between GC12 and GC3 (p > 0.05). Correspondence analysis and ENc-plot results showed that natural selection dominated over mutation in the codon usage bias. The tree of cluster analysis based on RSCU was concordant with dendrogram based on genomic BLAST by neighbor-joining method. By comparative analysis, about 50 highly expressed genes that were orthologs across all 12 strains were found in the top 5% of high CAI value. Based on these CAI values, we infer that RA contains a number of predicted highly expressed coding sequences, involved in transcriptional regulation and metabolism, reflecting their requirement for dealing with diverse environmental conditions. These results provide some useful information on the mechanisms that contribute to codon usage bias and evolution of RA. PMID:27517915

  10. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans.

    PubMed Central

    Santos, M A; Tuite, M F

    1995-01-01

    Previous studies have shown that the yeast Candida albicans encodes a unique seryl-tRNA(CAG) that should decode the leucine codon CUG as serine. However, in vitro translation of several different CUG-containing mRNAs in the presence of this unusual seryl-tRNA(CAG) result in an apparent increase in the molecular weight of the encoded polypeptides as judged by SDS-PAGE even though the molecular weight of serine is lower than that of leucine. A possible explanation for this altered electrophoretic mobility is that the CUG codon is decoded as modified serine in vitro. To elucidate the nature of CUG decoding in vivo, a reporter system based on the C. albicans gene (RBP1) encoding rapamycin-binding protein (RBP), coupled to the promoter of the C. albicans TEF3 gene, was utilized. Sequencing and mass-spectrometry analysis of the recombinant RBP expressed in C. albicans demonstrated that the CUG codon was decoded exclusively as serine while the related CUU codon was translated as leucine. A database search revealed that 32 out of the 65 C. albicans gene sequences available have CUG codons in their open reading frames. The CUG-containing genes do not belong to any particular gene family. Thus the amino acid specified by the CUG codon has been reassigned within the mRNAs of C. albicans. We argue here that this unique genetic code change in cellular mRNAs cannot be explained by the 'Codon Reassignment Theory'. Images PMID:7784200

  11. Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery

    PubMed Central

    Takacs, Julie E.; Neary, Timothy B.; Ingolia, Nicholas T.; Saini, Adesh K.; Martin-Marcos, Pilar; Pelletier, Jerry; Hinnebusch, Alan G.; Lorsch, Jon R.

    2011-01-01

    Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui−. No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-AUG start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a UUG. The compounds were also found to exacerbate increased use of UUG as a start codon (Sui− phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor (eIF) 1, or by mutation in eIF1. Furthermore, the effects of the compounds are suppressed by overexpressing eIF1, which is known to restore the fidelity of start codon selection in strains harboring Sui− mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting AUG as the start codon. PMID:21220547

  12. Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery.

    PubMed

    Takacs, Julie E; Neary, Timothy B; Ingolia, Nicholas T; Saini, Adesh K; Martin-Marcos, Pilar; Pelletier, Jerry; Hinnebusch, Alan G; Lorsch, Jon R

    2011-03-01

    Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui(-). No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-AUG start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a UUG. The compounds were also found to exacerbate increased use of UUG as a start codon (Sui(-) phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor (eIF) 1, or by mutation in eIF1. Furthermore, the effects of the compounds are suppressed by overexpressing eIF1, which is known to restore the fidelity of start codon selection in strains harboring Sui(-) mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting AUG as the start codon.

  13. Codon Optimization OnLine (COOL): a web-based multi-objective optimization platform for synthetic gene design.

    PubMed

    Chin, Ju Xin; Chung, Bevan Kai-Sheng; Lee, Dong-Yup

    2014-08-01

    Codon optimization has been widely used for designing synthetic genes to improve their expression in heterologous host organisms. However, most of the existing codon optimization tools consider a single design criterion and/or implement a rather rigid user interface to yield only one optimal sequence, which may not be the best solution. Hence, we have developed Codon Optimization OnLine (COOL), which is the first web tool that provides the multi-objective codon optimization functionality to aid systematic synthetic gene design. COOL supports a simple and flexible interface for customizing various codon optimization parameters such as codon adaptation index, individual codon usage and codon pairing. In addition, users can visualize and compare the optimal synthetic sequences with respect to various fitness measures. User-defined DNA sequences can also be compared against the COOL optimized sequences to show the extent by which the user's sequences can be further improved. COOL is free to academic and non-commercial users and licensed to others for a fee by the National University of Singapore. Accessible at http://bioinfo.bti.a-star.edu.sg/COOL/ CONTACT: cheld@nus.edu.sg Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Large-scale analysis of conserved rare codon clusters suggests an involvement in co-translational molecular recognition events.

    PubMed

    Chartier, Matthieu; Gaudreault, Francis; Najmanovich, Rafael

    2012-06-01

    An increasing amount of evidence from experimental and computational analysis suggests that rare codon clusters are functionally important for protein activity. Most of the studies on rare codon clusters were performed on a limited number of proteins or protein families. In the present study, we present the Sherlocc program and how it can be used for large scale protein family analysis of evolutionarily conserved rare codon clusters and their relation to protein function and structure. This large-scale analysis was performed using the whole Pfam database covering over 70% of the known protein sequence universe. Our program Sherlocc, detects statistically relevant conserved rare codon clusters and produces a user-friendly HTML output. Statistically significant rare codon clusters were detected in a multitude of Pfam protein families. The most statistically significant rare codon clusters were predominantly identified in N-terminal Pfam families. Many of the longest rare codon clusters are found in membrane-related proteins which are required to interact with other proteins as part of their function, for example in targeting or insertion. We identified some cases where rare codon clusters can play a regulating role in the folding of catalytically important domains. Our results support the existence of a widespread functional role for rare codon clusters across species. Finally, we developed an online filter-based search interface that provides access to Sherlocc results for all Pfam families. The Sherlocc program and search interface are open access and are available at http://bcb.med.usherbrooke.ca

  15. HIV-1 gag expression is quantitatively dependent on the ratio of native and optimized codons.

    PubMed

    Kofman, Alexander; Graf, Marcus; Bojak, Alexandra; Deml, Ludwig; Bieler, Kurt; Kharazova, Alexandra; Wolf, Hans; Wagner, Ralf

    2003-01-01

    There is a significant variation of codon usage bias among different species and even among genes within the same organisms. Codon optimization, this is, gene redesigning with the use of codons preferred for the specific expression system, results in improved expression of heterologous genes in bacteria, plants, yeast, mammalian cells, and transgenic animals. The mechanisms preventing expression of genes with rare or low-usage codons at adequate levels are not completely elucidated. Human immunodeficiency virus (HIV) represents an interesting model for studying how differences in codon usage affect gene expression in heterologous systems. Construction of synthetic genes with optimized codons demonstrated that the codon-usage effects might be a major impediment to the efficient expression of HIV gag/pol and env gene products in mammalian cells. According to another hypothesis, the poor expression of HIV structural proteins even without HIV context is attributed to the so-called cis-acting inhibitory elements (INS), which are located within the protein-coding region. They consist of AU-rich sequences and may be inactivated through the introduction of multiple mutations over the large regions of gag gene. In our work, we evaluated expression of hybrid HIV-1 gag mRNAs where wild-type (A-rich) gag sequences were combined with artificial sequences. In such "humanized" gag fragments with adapted codon usage, AT-content was significantly reduced in favor of G and C nucleotides without any changes in protein sequence. We show that wild-type gag sequences negatively influence expression of gag-reporter, and the addition of fragments with optimized codons to gag mRNA partially rescues its expression. The results demonstrate that the expression of HIV-1 gag is determined by the ratio of optimized and rare codons within mRNA. Our data also indicates that some wtgag fragments counteract the influence of the other wtgag sequences, which cause the inhibition of gag expression. The

  16. Nucleotide sequence conservation in paramyxoviruses; the concept of codon constellation.

    PubMed

    Rima, Bert K

    2015-05-01

    The stability and conservation of the sequences of RNA viruses in the field and the high error rates measured in vitro are paradoxical. The field stability indicates that there are very strong selective constraints on sequence diversity. The nature of these constraints is discussed. Apart from constraints on variation in cis-acting RNA and the amino acid sequences of viral proteins, there are other ones relating to the presence of specific dinucleotides such CpG and UpA as well as the importance of RNA secondary structures and RNA degradation rates. Recent other constraints identified in other RNA viruses, such as effects of secondary RNA structure on protein folding or modification of cellular tRNA complements, are also discussed. Using the family Paramyxoviridae, I show that the codon usage pattern (CUP) is (i) specific for each virus species and (ii) that it is markedly different from the host - it does not vary even in vaccine viruses that have been derived by passage in a number of inappropriate host cells. The CUP might thus be an additional constraint on variation, and I propose the concept of codon constellation to indicate the informational content of the sequences of RNA molecules relating not only to stability and structure but also to the efficiency of translation of a viral mRNA resulting from the CUP and the numbers and position of rare codons.

  17. Selection of AUG initiation codons differs in plants and animals.

    PubMed Central

    Lütcke, H A; Chow, K C; Mickel, F S; Moss, K A; Kern, H F; Scheele, G A

    1987-01-01

    The influence of the nucleotide at position -3 relative to the AUG initiation codon on the initiation of protein synthesis was studied in two different in vitro translation systems using synthetic mRNAs. The four mRNAs, transcribed from cDNAs directed by an SP6 promoter, were identical except for mutations at nucleotide -3. In each case, translation of mRNAs produced a single protein of Mr = 12,600. Relative translational efficiencies showed a hierarchy in the reticulocyte lysate system (100, 85, 61 and 38% for A, G, U and C in position -3, respectively) but no differences in the wheat germ system. Differential mRNA degradation or polypeptide chain elongation were excluded as causes of the differences observed in translation in the reticulocyte lysate. mRNA competition increased the differences observed in translational efficiencies in reticulocyte lysate but showed no effect in wheat germ. Analysis of 61 plant and 209 animal mRNA sequences revealed qualitative and quantitative differences between the consensus sequences surrounding AUG initiation codons. Whereas the consensus sequence for animals was CACCAUG that for plants was AACAAUGGC. Both the structural and functional findings suggest that the factors which select AUG initiation codons in plants and animals differ significantly. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3556162

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2016-01-01

    The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including “codon capture,” “genome streamlining,” and “ambiguous intermediate” theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNAAla containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. PMID:27197221

  20. Expected relative fitness and the adaptive topography of fluctuating selection.

    PubMed

    Lande, Russell

    2007-08-01

    Wright's adaptive topography describes gene frequency evolution as a maximization of mean fitness in a constant environment. I extended this to a fluctuating environment by unifying theories of stochastic demography and fluctuating selection, assuming small or moderate fluctuations in demographic rates with a stationary distribution, and weak selection among the types. The demography of a large population, composed of haploid genotypes at a single locus or normally distributed phenotypes, can then be approximated as a diffusion process and transformed to produce the dynamics of population size, N, and gene frequency, p, or mean phenotype, . The expected evolution of p or is a product of genetic variability and the gradient of the long-run growth rate of the population, , with respect to p or . This shows that the expected evolution maximizes , the mean Malthusian fitness in the average environment minus half the environmental variance in population growth rate. Thus, as a function of p or represents an adaptive topography that, despite environmental fluctuations, does not change with time. The haploid model is dominated by environmental stochasticity, so the expected maximization is not realized. Different constraints on quantitative genetic variability, and stabilizing selection in the average environment, allow evolution of the mean phenotype to undergo a stochastic maximization of . Although the expected evolution maximizes the long-run growth rate of the population, for a genotype or phenotype the long-run growth rate is not a valid measure of fitness in a fluctuating environment. The haploid and quantitative character models both reveal that the expected relative fitness of a type is its Malthusian fitness in the average environment minus the environmental covariance between its growth rate and that of the population.

  1. Discrepancy among the synonymous codons with respect to their selection as optimal codon in bacteria

    PubMed Central

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

    2016-01-01

    The different triplets encoding the same amino acid, termed as synonymous codons, are not equally abundant in a genome. Factors such as G + C% and tRNA are known to influence their abundance in a genome. However, the order of the nucleotide in each codon per se might also be another factor impacting on its abundance values. Of the synonymous codons for specific amino acids, some are preferentially used in the high expression genes that are referred to as the ‘optimal codons’ (OCs). In this study, we compared OCs of the 18 amino acids in 221 species of bacteria. It is observed that there is amino acid specific influence for the selection of OCs. There is also influence of phylogeny in the choice of OCs for some amino acids such as Glu, Gln, Lys and Leu. The phenomenon of codon bias is also supported by the comparative studies of the abundance values of the synonymous codons with same G + C. It is likely that the order of the nucleotides in the triplet codon is also perhaps involved in the phenomenon of codon usage bias in organisms. PMID:27426467

  2. Computational codon optimization of synthetic gene for protein expression

    PubMed Central

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  5. Career Adapt-Abilities Scale-USA Form: Psychometric Properties and Relation to Vocational Identity

    ERIC Educational Resources Information Center

    Porfeli, Erik J.; Savickas, Mark L.

    2012-01-01

    This article reports construction and initial validation of the United States form of the Career Adapt-Abilities Scale (CAAS). The CAAS consists of four scales, each with six items, which measure concern, control, curiosity, and confidence as psychosocial resources for managing occupational transitions, developmental tasks, and work traumas.…

  6. Career Adapt-Abilities Scale-USA Form: Psychometric Properties and Relation to Vocational Identity

    ERIC Educational Resources Information Center

    Porfeli, Erik J.; Savickas, Mark L.

    2012-01-01

    This article reports construction and initial validation of the United States form of the Career Adapt-Abilities Scale (CAAS). The CAAS consists of four scales, each with six items, which measure concern, control, curiosity, and confidence as psychosocial resources for managing occupational transitions, developmental tasks, and work traumas.…

  7. Coupling between protein level selection and codon usage optimization in the evolution of bacteria and archaea.

    PubMed

    Ran, Wenqi; Kristensen, David M; Koonin, Eugene V

    2014-03-25

    The relationship between the selection affecting codon usage and selection on protein sequences of orthologous genes in diverse groups of bacteria and archaea was examined by using the Alignable Tight Genome Clusters database of prokaryote genomes. The codon usage bias is generally low, with 57.5% of the gene-specific optimal codon frequencies (Fopt) being below 0.55. This apparent weak selection on codon usage contrasts with the strong purifying selection on amino acid sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most of the genomes compared, a limited but statistically significant negative correlation between Fopt and dN/dS was observed, which is indicative of a link between selection on protein sequence and selection on codon usage. The strength of the coupling between the protein level selection and codon usage bias showed a strong positive correlation with the genomic GC content. Combined with previous observations on the selection for GC-rich codons in bacteria and archaea with GC-rich genomes, these findings suggest that selection for translational fine-tuning could be an important factor in microbial evolution that drives the evolution of genome GC content away from mutational equilibrium. This type of selection is particularly pronounced in slowly evolving, "high-status" genes. A significantly stronger link between the two aspects of selection is observed in free-living bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and transporters than in informational genes. These differences might reflect the special importance of translational fine-tuning for the adaptability of gene expression to environmental changes. The results of this work establish the coupling between protein level selection and selection for translational optimization as a distinct and potentially important factor in microbial evolution. IMPORTANCE Selection affects the evolution of microbial genomes at many levels, including both

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

    PubMed

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

    2015-11-01

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

  9. Efficient expression of gene variants that harbour AGA codons next to the initiation codon

    PubMed Central

    Zamora-Romo, Efraín; Cruz-Vera, Luis Rogelio; Vivanco-Domínguez, Serafín; Magos-Castro, Marco Antonio; Guarneros, Gabriel

    2007-01-01

    In an effort to improve the knowledge about the rules which direct the effect of the early ORF sequences on translation efficiency, we have analyzed the effect of pairs of the six arginine codons at the second and third positions on the expression of lacZ variants. Whereas the pairs of identical AGA or AGG codons were favorable for the gene expression, identical pairs of each of the four CGN codons were very inefficient. This result was unexpected because tandems of AGA or AGG codons located in more internal gene positions provoke deficient expression whilst internally located CGU and CGC are the most abundant and efficiently translated arginine codons. The mixed combinations of AGA and each of the CGN codons usually resulted in efficient rates of lacZ expression independently of the peptidyl-tRNA propensity to dissociate from the ribosome. Thus, the variant harboring the pair of AGA codons was expressed as efficiently as the variant carrying a pair of AAA codons in the same positions, a configuration reported as one of the most common and efficient for gene expression. We explain these results assuming that the presence of adenines in these early positions enhance gene expression. As expected, specific mRNA levels correlated with the intensity of lacZ expression for each variant. However, the induction of lacZ AGA AGA gene in pth cells accumulated peptidyl-tRNAArg4 as well as a short 5′-proximal lacZ mRNA fragment suggesting ribosome stalling due to depletion of aminoacylated-tRNAArg4. PMID:17726048

  10. Codon expansion and systematic transcriptional deletions produce tetra-, pentacoded mitochondrial peptides.

    PubMed

    Seligmann, Hervé

    2015-12-21

    Genes include occasionally isolated codons with a fourth (and fifth) silent nucleotide(s). Assuming tetracodons, translated hypothetical peptides align with regular GenBank proteins; predicted tetracodons coevolve with predicted tRNAs with expanded anticodons in each mammal, Drosophila and Lepidosauria mitogenomes, GC contents and with lepidosaurian body temperatures, suggesting that expanded codons are an adaptation of translation to high temperature. Hypothetically, continuous stretches of tetra- and pentacodons code for peptides. Both systematic nucleotide deletions during transcription, and translation by tRNAs with expanded anticodons could produce these peptides. Reanalyses of human nanoLc mass spectrometry peptidome data detect numerous tetra- and pentapeptides translated from the human mitogenome. These map preferentially on (BLAST-detected) human RNAs matching the human mitogenome, assuming systematic mono- and dinucleotide deletions after each third nucleotide (delRNAs). Translation by expanded anticodons is incompatible with silent nucleotides in the midst rather than at codon 3' extremity. More than 1/3 of detected tetra- and pentapeptides assume silent positions at codon extremity, suggesting that both mechanisms, regular translation of delRNAs and translation of regular RNAs by expanded anticodons, produce this peptide subgroup. Results show that systematically deleting polymerization occurs, and confirm serial translation of expanded codons. Non-canonical transcriptions and translations considerably expand the coding potential of DNA and RNA sequences.

  11. Codon and Amino Acid Usage Are Shaped by Selection Across Divergent Model Organisms of the Pancrustacea

    PubMed Central

    Whittle, Carrie A.; Extavour, Cassandra G.

    2015-01-01

    In protein-coding genes, synonymous codon usage and amino acid composition correlate to expression in some eukaryotes, and may result from translational selection. Here, we studied large-scale RNA-seq data from three divergent arthropod models, including cricket (Gryllus bimaculatus), milkweed bug (Oncopeltus fasciatus), and the amphipod crustacean Parhyale hawaiensis, and tested for optimization of codon and amino acid usage relative to expression level. We report strong signals of AT3 optimal codons (those favored in highly expressed genes) in G. bimaculatus and O. fasciatus, whereas weaker signs of GC3 optimal codons were found in P. hawaiensis, suggesting selection on codon usage in all three organisms. Further, in G. bimaculatus and O. fasciatus, high expression was associated with lowered frequency of amino acids with large size/complexity (S/C) scores in favor of those with intermediate S/C values; thus, selection may favor smaller amino acids while retaining those of moderate size for protein stability or conformation. In P. hawaiensis, highly transcribed genes had elevated frequency of amino acids with large and small S/C scores, suggesting a complex dynamic in this crustacean. In all species, the highly transcribed genes appeared to favor short proteins, high optimal codon usage, specific amino acids, and were preferentially involved in cell-cycling and protein synthesis. Together, based on examination of 1,680,067, 1,667,783, and 1,326,896 codon sites in G. bimaculatus, O. fasciatus, and P. hawaiensis, respectively, we conclude that translational selection shapes codon and amino acid usage in these three Pancrustacean arthropods. PMID:26384771

  12. Influence of codon usage bias on FGLamide-allatostatin mRNA secondary structure.

    PubMed

    Martínez-Pérez, Francisco; Bendena, William G; Chang, Belinda S W; Tobe, Stephen S

    2011-03-01

    The FGLamide allatostatins (ASTs) are invertebrate neuropeptides which inhibit juvenile hormone biosynthesis in Dictyoptera and related orders. They also show myomodulatory activity. FGLamide AST nucleotide frequencies and codon bias were investigated with respect to possible effects on mRNA secondary structure. 367 putative FGLamide ASTs and their potential endoproteolytic cleavage sites were identified from 40 species of crustaceans, chelicerates and insects. Among these, 55% comprised only 11 amino acids. An FGLamide AST consensus was identified to be (X)(1→16)Y(S/A/N/G)FGLGKR, with a strong bias for the codons UUU encoding for Phe and AAA for Lys, which can form strong Watson-Crick pairing in all peptides analyzed. The physical distance between these codons favor a loop structure from Ser/Ala-Phe to Lys-Arg. Other loop and hairpin loops were also inferred from the codon frequencies in the N-terminal motif, and the first amino acids from the C-terminal motif, or the dibasic potential endoproteolytic cleavage site. Our results indicate that nucleotide frequencies and codon usage bias in FGLamide ASTs tend to favor mRNA folds in the codon sequence in the C-terminal active peptide core and at the dibasic potential endoproteolytic cleavage site. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Variation in synonymous codon usage in Paenibacillus sp. 32O-W genome

    PubMed Central

    Deb, Sushanta; Basak, Surajit

    2016-01-01

    Paenibacillus sp. 32O-W, which is attributed for biodesulfurization of petroleum, has 56.34% genomic G+C content. Correspondence analysis on Relative Synonymous Codon Usage (RSCU) of the Paenibacillus sp. 32O-W genome has revealed the two different trends of codon usage variation. Two sets of genes have been identified representing the two distinct pattern of codon usage in this bacterial genome. We have measured several codon usage indices to understand the influencing factors governing the differential pattern of codon usage variation in this bacterial genome. We also observed significant differences in many protein properties between the two gene sets (e.g., hydrophobicity, protein biosynthetic cost, protein aggregation propensity). The compositional difference between the two sets of genes and the difference in their potential gene expressivity are the driving force for the differences in protein biosynthetic cost and aggregation propensity. Based on our results we argue that codon usage variation in Paenibacillus sp. 32O-W genome is actually influenced by both mutational bias and translational selection. PMID:28293070

  14. Stop codon reassignments in the wild.

    PubMed

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

    2014-05-23

    The canonical genetic code is assumed to be deeply conserved across all domains of life with very few exceptions. By scanning 5.6 trillion base pairs of metagenomic data for stop codon reassignment events, we detected recoding in a substantial fraction of the >1700 environmental samples examined. We observed extensive opal and amber stop codon reassignments in bacteriophages and of opal in bacteria. Our data indicate that bacteriophages can infect hosts with a different genetic code and demonstrate phage-host antagonism based on code differences. The abundance and diversity of genetic codes present in environmental organisms should be considered in the design of engineered organisms with altered genetic codes in order to preclude the exchange of genetic information with naturally occurring species.

  15. Stop Codon Reassignment in the Wild

    SciTech Connect

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

    2014-03-21

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

  16. Classrooms as Complex Adaptive Systems: A Relational Model

    ERIC Educational Resources Information Center

    Burns, Anne; Knox, John S.

    2011-01-01

    In this article, we describe and model the language classroom as a complex adaptive system (see Logan & Schumann, 2005). We argue that linear, categorical descriptions of classroom processes and interactions do not sufficiently explain the complex nature of classrooms, and cannot account for how classroom change occurs (or does not occur), over…

  17. Relational benefits of relational aggression: adaptive and maladaptive associations with adolescent friendship quality.

    PubMed

    Banny, Adrienne M; Heilbron, Nicole; Ames, Angharad; Prinstein, Mitchell J

    2011-07-01

    Two longitudinal studies examined associations between relational aggression and friendship quality during adolescence. In Study 1, 62 adolescents in Grades 6 (25.8%), 7 (32.3%), and 8 (41.9%) completed assessments of friendship affiliations, relational and overt aggression, and friendship quality at 2 time points, 1 year apart. Results using actor partner interdependence modeling indicated that high levels of relational aggression predicted increases in self-reported positive friendship quality 1 year later. In Study 2, 56 adolescents in Grades 9 (66.7%) and 10 (33.3%) attended a laboratory session with a friend in which their conversations were videotaped and coded for relationally aggressive talk. Target adolescents completed measures of positive and negative friendship quality during the laboratory session and during a follow-up phone call 6 months later. Analyses revealed that high levels of relationally aggressive talk at Time 1 predicted increases in negative friendship quality 6 months later. In addition, among adolescents involved in a reciprocal best friendship, high levels of observed relationally aggressive talk predicted increases in positive friendship quality over time. Taken together, these studies provide support for the idea that relational aggression may be associated with adaptive as well as maladaptive outcomes within the dyadic context of adolescent friendship. PsycINFO Database Record (c) 2011 APA, all rights reserved

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

    PubMed

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

    2015-08-01

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

  19. A critical analysis of codon optimization in human therapeutics.

    PubMed

    Mauro, Vincent P; Chappell, Stephen A

    2014-11-01

    Codon optimization describes gene engineering approaches that use synonymous codon changes to increase protein production. Applications for codon optimization include recombinant protein drugs and nucleic acid therapies, including gene therapy, mRNA therapy, and DNA/RNA vaccines. However, recent reports indicate that codon optimization can affect protein conformation and function, increase immunogenicity, and reduce efficacy. We critically review this subject, identifying additional potential hazards including some unique to nucleic acid therapies. This analysis highlights the evolved complexity of codon usage and challenges the scientific bases for codon optimization. Consequently, codon optimization may not provide the optimal strategy for increasing protein production and may decrease the safety and efficacy of biotech therapeutics. We suggest that the use of this approach is reconsidered, particularly for in vivo applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Age-Related Differences in Locomotor Strategies During Adaptive Walking.

    PubMed

    Lowry, Kristin A; Sebastian, Katherine; Perera, Subashan; Van Swearingen, Jessie; Smiley-Oyen, Ann L

    2016-11-21

    Simultaneous control of lower limb stepping movements and trunk motion is important for skilled walking; adapting gait to environmental constraints requires frequent alternations in stepping and trunk motion. These alterations provide a window into the locomotor strategies adopted by the walker. The authors examined gait strategies in young and healthy older adults when manipulating step width. Anteroposterior (AP) and mediolateral (ML) smoothness (quantified by harmonic ratios) and stepping consistency (quantified by gait variability) were analyzed during narrow and wide walking while controlling cadence to preferred pace. Results indicated older adults preserved ML smoothness at the expense of AP smoothness, shortened their steps, and exhibited reduced stepping consistency. The authors conclude that older adults prioritized ML control over forward progression during adaptive walking challenges.

  1. Generating Shifting Workloads to Benchmark Adaptability in Relational Database Systems

    NASA Astrophysics Data System (ADS)

    Rabl, Tilmann; Lang, Andreas; Hackl, Thomas; Sick, Bernhard; Kosch, Harald

    A large body of research concerns the adaptability of database systems. Many commercial systems already contain autonomic processes that adapt configurations as well as data structures and data organization. Yet there is virtually no possibility for a just measurement of the quality of such optimizations. While standard benchmarks have been developed that simulate real-world database applications very precisely, none of them considers variations in workloads produced by human factors. Today’s benchmarks test the performance of database systems by measuring peak performance on homogeneous request streams. Nevertheless, in systems with user interaction access patterns are constantly shifting. We present a benchmark that simulates a web information system with interaction of large user groups. It is based on the analysis of a real online eLearning management system with 15,000 users. The benchmark considers the temporal dependency of user interaction. Main focus is to measure the adaptability of a database management system according to shifting workloads. We will give details on our design approach that uses sophisticated pattern analysis and data mining techniques.

  2. Synonymous codon usage, GC(3), and evolutionary patterns across plastomes of three pooid model species: emerging grass genome models for monocots.

    PubMed

    Sablok, Gaurav; Nayak, Kinshuk Chandra; Vazquez, Franck; Tatarinova, Tatiana V

    2011-10-01

    We have analyzed factors affecting the codon usage pattern of the chloroplasts genomes of representative species of pooid grass family. Correspondence analysis of relative synonymous codon usages (RSCU) showed that genes on secondary axis were correlated with their GC(3S) values (all r > 0.3, p < 0.05), indicating mutational bias as an important selective force that shaped the variation in the codon usage among chloroplast genes. The Nc-plot showed that although a majority of the points with low-Nc values were lying below the expected curve, a few genes lied on the expected curve. Nc plot clearly showed that mutational bias plays a major role in codon biology across the monocot plastomes. The hydrophobicity and aromaticity of encoded proteins of each species were found to be other factors of codon usage variation. In the view of above light, besides natural selection, several other factors also likely to be involved in determining the selective constraints on codon bias in plastomes of pooid grass genomes. In addition, five codons (B. distachyon), seven codons (H. vulgare), and four codons (T. aestivum) were identified as optimal codons of the three grass chloroplasts. To identify genes evolving under positive selection, rates of nonsynonymous substitutions (Ka) and synonymous substitutions (Ks) were computed for all groups of orthologous gene pairs.

  3. Maladaptive Behaviors Related to Adaptive Decline in Aging Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Urv, Tiina K.; Zigman, Warren B.; Silverman, Wayne

    2003-01-01

    Changes in patterns of maladaptive behavior related to age-associated adaptive declines were investigated in 529 adults with mental retardation (ages 30 to 84), 202 with Down syndrome. Certain maladaptive behaviors were related to the onset of adaptive declines, (e.g., lack of boundaries). Findings suggest similarities in the course of…

  4. Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

    PubMed Central

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

    2010-01-01

    Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness. PMID:20221432

  5. Codon optimization of genes for efficient protein expression in mammalian cells by selection of only preferred human codons.

    PubMed

    Inouye, Satoshi; Sahara-Miura, Yuiko; Sato, Jun-ichi; Suzuki, Takahiro

    2015-05-01

    A simple design method for codon optimization of genes to express a heterologous protein in mammalian cells is described. Codon optimization was performed by choosing only codons preferentially used in humans and with over 60% GC content, and the method was named the "preferred human codon-optimized method." To test our simple rule for codon optimization, the preferred human codon-optimized genes for six proteins containing photoproteins (aequorin and clytin II) and luciferases (Gaussia luciferase, Renilla luciferase, and firefly luciferases from Photinus pyralis and Luciola cruciata) were chemically synthesized and transiently expressed in Chinese hamster ovary-K1 cells. All preferred human codon-optimized genes showed higher luminescence activity than the corresponding wild-type genes. Our simple design method could be used to improve protein expression in mammalian cells efficiently. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Analysis of synonymous codon usage patterns in sixty-four different bivalve species

    PubMed Central

    De Moro, Gianluca; Venier, Paola; Pallavicini, Alberto

    2015-01-01

    Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates. PMID:26713259

  7. Analysis of synonymous codon usage patterns in sixty-four different bivalve species.

    PubMed

    Gerdol, Marco; De Moro, Gianluca; Venier, Paola; Pallavicini, Alberto

    2015-01-01

    Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates.

  8. Analysis of synonymous codon usage bias and phylogeny of coat protein gene in banana bract mosaic virus isolates.

    PubMed

    Patil, Atul B; Dalvi, Vijayendra S; Mishra, Akhilesh A; Krishna, Bal; Azeez, Abdul

    2017-06-01

    The banana is one of the world's most important livelihood crops. Banana plants are principally infected by four virus species, Banana bunchy top virus (genus Babuvirus), Cucumber mosaic virus (genus Cucumovirus), Banana streak virus (genus Badnavirus) and Banana bract mosaic virus (genus Potyvirus). The objective of this study is to understand the codon usage pattern and phylogeny of coat protein gene in different banana bract mosaic virus (BBrMV) isolates. The BBrMV Coat Protein (CP) gene was amplified from BBrMV infected banana plant samples collected from different districts of Tamil Nadu and Karnataka, India. Six new BBrMV isolates were submitted to National Center for Biotechnology Information. Phylogenetic analysis and codon usage indices were studied along with other isolates of BBrMV. Phylogenetic analysis of CP genes shows that most of BBrMV isolates are closely related to each other except KF385484.1 and KF385478.1. Relative codon usage patterns among different BBrMV isolates were calculated by software CodonW version 1.4.2. In BBrMV, codons with A-ended or U ended are the most preferential except the Leu and Gln whose optimized codons are CAG and UUG ending by G. The codon usage patterns of BBrMV isolates are principally influenced by mutational bias; however, compositional constraints along with mutational bias also play a major role.

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

    PubMed

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

    2015-12-22

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

  10. Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase.

    PubMed

    Goudsmit, J; De Ronde, A; Ho, D D; Perelson, A S

    1996-08-01

    We monitored a subject newly infected with a zidovudine-resistant human immunodeficiency virus type 1 strain and found that in the absence of drug, the viral population with the resistance-conferring tyrosine (TAC) codon 215 of reverse transcriptase was gradually replaced. By using standard formulas to model the effects of selection at a single locus in an asexual haploid population, the relative fitness gain of the viral population with a single mutation at codon 215 creating a serine (TCC) was calculated. We concluded that a viral population with a serine at reverse transcriptase codon 215 conferring zidovudine sensitivity was between 0.4 and 2.3% more fit.

  11. Mathematics of adaptive wavelet transforms: relating continuous with discrete transforms

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Telfer, Brian A.

    1994-07-01

    We prove several theorems and construct explicitly the bridge between the continuous and discrete adaptive wavelet transform (AWT). The computational efficiency of the AWT is a result of its compact support closely matching linearly the signal's time-frequency characteristics, and is also a result of a larger redundancy factor of the superposition-mother s(x) (super-mother), created adaptively by a linear superposition of other admissible mother wavelets. The super-mother always forms a complete basis, but is usually associated with a higher redundancy number than its constituent complete orthonormal bases. The robustness of super-mother suffers less noise contamination (since noise is everywhere, and a redundant sampling by bandpassings can suppress the noise and enhance the signal). Since the continuous super-mother has been created off-line by AWT (using least-mean- squares neural nets), we wish to accomplish fast AWT on line. Thus, we formulate AWT in discrete high-pass (H) and low-pass (L) filter bank coefficients via the quadrature mirror filter, (QMF), a digital subband lossless coding. A linear combination of two special cases of complete biorthogonal normalized (Cbi-ON) QMF [L(z), H(z), L+(z), H+(z)], called (alpha) -bank and (Beta) -bank, becomes a hybrid a(alpha) + b(Beta) -bank (for any real positive constants a and b) that is still admissible, meaning Cbi-ON and lossless. Finally, the power of AWT is the implementation by means of wavelet chips and neurochips, in which each node is a daughter wavelet similar to a radial basis function using dyadic affine scaling.

  12. Large-scale analysis of conserved rare codon clusters suggests an involvement in co-translational molecular recognition events

    PubMed Central

    Chartier, Matthieu; Gaudreault, Francis; Najmanovich, Rafael

    2012-01-01

    Motivation: An increasing amount of evidence from experimental and computational analysis suggests that rare codon clusters are functionally important for protein activity. Most of the studies on rare codon clusters were performed on a limited number of proteins or protein families. In the present study, we present the Sherlocc program and how it can be used for large scale protein family analysis of evolutionarily conserved rare codon clusters and their relation to protein function and structure. This large-scale analysis was performed using the whole Pfam database covering over 70% of the known protein sequence universe. Our program Sherlocc, detects statistically relevant conserved rare codon clusters and produces a user-friendly HTML output. Results: Statistically significant rare codon clusters were detected in a multitude of Pfam protein families. The most statistically significant rare codon clusters were predominantly identified in N-terminal Pfam families. Many of the longest rare codon clusters are found in membrane-related proteins which are required to interact with other proteins as part of their function, for example in targeting or insertion. We identified some cases where rare codon clusters can play a regulating role in the folding of catalytically important domains. Our results support the existence of a widespread functional role for rare codon clusters across species. Finally, we developed an online filter-based search interface that provides access to Sherlocc results for all Pfam families. Availability: The Sherlocc program and search interface are open access and are available at http://bcb.med.usherbrooke.ca Contact: rafael.najmanovich@usherbrooke.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22467916

  13. Energetics of codon-anticodon recognition on the small ribosomal subunit.

    PubMed

    Almlöf, Martin; Andér, Martin; Aqvist, Johan

    2007-01-09

    Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons, are analyzed here using explicit solvent molecular dynamics simulations together with the linear interaction energy (LIE) method. The calculated binding free energies are in excellent agreement with experimental binding constants and reproduce the relative effects of mismatches in the first and second codon position versus a mismatch at the wobble position. The simulations further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with the Phe UUU codon. It is also found that the ribosome significantly enhances the intrinsic stability differences of codon-anticodon complexes in aqueous solution. Structural analysis of the simulations confirms the previously suggested importance of the universally conserved nucleotides A1492, A1493, and G530 in the decoding process.

  14. Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O)

    PubMed Central

    Ahn, Insung; Bae, Se-Eun

    2011-01-01

    We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 from various region of the world. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogenetic relationships in the same serotype (serotype O). Moreover, while the SSC and EMC values of FMDVs decreased according to phylogenetic distance, G + C composition at the third codon position was strictly conserved. Although there was little variation among the SSC values of 18 amino acids, more dynamic differences were observed in EMC values. The EMC values of 4- and 6-fold degenerate amino acids showed significantly lower values while most 2-fold degenerate amino acids showed no significant difference. Our findings suggest that different EMC patterns among the 18 amino acids might be an important factor in determining the direction of evolution in FMDV. PMID:21825834

  15. New insights into the codon usage patterns of the bactericidal/permeability-increasing (BPI) gene across nine species.

    PubMed

    Qin, Wei-Yun; Gan, Li-Na; Xia, Ri-Wei; Sun, Shou-Yong; Zhu, Guo-Qiang; Wu, Sheng-Long; Bao, Wen-Bin

    2017-03-20

    Bactericidal/permeability-increasing (BPI) protein is a member of a new generation of proteins known as super-antibiotics that are implicated as endotoxin neutralising agents. Non-uniform usage of synonymous codons for a specific amino acid during translation of a protein is known as codon usage bias (CUB). Analysis of CUB and compositional dynamics of coding sequences could contribute to a better understanding of the molecular mechanism and the evolution of a particular gene. In this study, we performed CUB analysis of the complete coding sequences of the BPI gene from nine different species. The codon usage patterns of BPI across different species were found to be influenced by GC bias, particularly GC3s, with a moderate bias in the codon usage of BPI. We found significant similarities in the codon usage patterns in BPI gene among closely related species, such as Sus_scrofa and Bos_taurus. Moreover, we observed evolutionary conservation of the most over-represented codon CUG for the amino acid leucine in the BPI gene across all species. In conclusion, our analysis provides a novel insight into the codon usage patterns of BPI. This information facilitates an improved understanding of the structural, functional and evolutionary significance of BPI gene among species, and provides a theoretical reference for developing antiseptic drug proteins with high efficiency across species.

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

    PubMed

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

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

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

    PubMed Central

    2006-01-01

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

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

    PubMed

    Mitreva, Makedonka; Wendl, Michael C; Martin, John; Wylie, Todd; Yin, Yong; Larson, Allan; Parkinson, John; Waterston, Robert H; McCarter, James P

    2006-01-01

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

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

    PubMed

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

    2003-06-27

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

  20. Relative age effect and soccer refereeing: a 'strategic adaptation' of relatively younger children?

    PubMed

    Delorme, Nicolas; Radel, Rémi; Raspaud, Michel

    2013-01-01

    Previous research suggested that the relative age effect (RAE) has a psychological influence on children and their decision to engage in a particular sport. Relatively younger children seem to have lower self-esteem. Indeed, because of the disadvantages of being younger, it is assumed that these players experience more situations of failure and inferiority. Because of these negative performance cues, it is likely that these young players feel less competent, which eventually leads to a higher dropout rate. These children can also decide to participate in sports in which physical attributes are less important. This shift from one sport to another can be interpreted as a 'strategic adaptation'. The purpose of this study was thus to investigate whether refereeing could be another form of 'strategic adaptation'. If a child chooses a specific sport but then does not feel competent enough to be a player, refereeing might be an alternate path followed to stay in the environment of a sport they like. Given the minimal age limits for refereeing, two hypotheses were formulated: (1) 'reversed' RAE would be observed in district referees younger than 18 years old and (2) no RAE would be observed in district referees older than 18 years old, regional referees and national referees. The birthdates of all official male soccer referees (n=13,952) were collected from the federation database. Results show that the distribution of all district referees was significantly unbalanced (χ(2)=18.73, df=3, P<0.001) with an over-representation of individuals who were born in the second half of the competitive year. As expected, this imbalance was exclusively located in district referees of 18 years old and less (χ(2)=8.03, df=3, P<0.05), while the distribution was uniform for adults (χ(2)=5.17, df=3, P<0.16). Concerning regional referees (χ(2)=2.09, df=3, P<0.554) and national referees (χ(2)=3.75, df=3, P<0.290), the results also provide support for our initial hypothesis as uniform

  1. A methodological survey identified eight proposed frameworks for the adaptation of health related guidelines.

    PubMed

    Darzi, Andrea; Abou-Jaoude, Elias A; Agarwal, Arnav; Lakis, Chantal; Wiercioch, Wojtek; Santesso, Nancy; Brax, Hneine; El-Jardali, Fadi; Schünemann, Holger J; Akl, Elie A

    2017-06-01

    five key steps strategy for adaptation of guidelines to the local context. The SGR method consists of nine steps and takes into consideration both methodological gaps and context-specific normative issues in source guidelines. We identified through searching personal files two abandoned methods. We identified and described eight proposed frameworks for the adaptation of health-related guidelines. There is a need to evaluate these different frameworks to assess rigor, efficiency, and transparency of their proposed processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Computer modeling describes gravity-related adaptation in cell cultures.

    PubMed

    Alexandrov, Ludmil B; Alexandrova, Stoyana; Usheva, Anny

    2009-12-16

    Questions about the changes of biological systems in response to hostile environmental factors are important but not easy to answer. Often, the traditional description with differential equations is difficult due to the overwhelming complexity of the living systems. Another way to describe complex systems is by simulating them with phenomenological models such as the well-known evolutionary agent-based model (EABM). Here we developed an EABM to simulate cell colonies as a multi-agent system that adapts to hyper-gravity in starvation conditions. In the model, the cell's heritable characteristics are generated and transferred randomly to offspring cells. After a qualitative validation of the model at normal gravity, we simulate cellular growth in hyper-gravity conditions. The obtained data are consistent with previously confirmed theoretical and experimental findings for bacterial behavior in environmental changes, including the experimental data from the microgravity Atlantis and the Hypergravity 3000 experiments. Our results demonstrate that it is possible to utilize an EABM with realistic qualitative description to examine the effects of hypergravity and starvation on complex cellular entities.

  3. Improved production of (R)-1-phenyl-1,2-ethanediol by a codon-optimized R-specific carbonyl reductase from Candida parapsilosis in Escherichia coli.

    PubMed

    Zhang, Rongzhen; Xu, Yan; Geng, Yawei; Wang, Shanshan; Sun, Ying; Xiao, Rong

    2010-03-01

    An R-specific carbonyl reductase from Candida parapsilosis (CprCR) catalyzes the transformation of (R)-1-phenyl-1,2-ethanediol from 2-hydroxyacetophenone. The gene rcr coding CprCR contains a few codons rarely used by Escherichia coli. In order to improve chiral alcohol production, three codon variants Delta24, aRCR, and mRCR of CprCR were designed through truncation of 4-27 bp disorder sequence at the 5'-terminus or/and adaption of nine rare codons. The effects of codon optimization on enzyme activity, protein production, and biotransformation were studied. Among these three types, the disorder sequence-truncated and rare codon-adapted variant mRCR presents the highest enzyme activity. When compared with CprCR, mRCR showed an increase of 35.6% in the total activity of cell-free extracts. The specific activity of mRCR presented similar increase in the cell-free extract with purified protein, which suggested that the codon optimization caused positive effect on protein productivity of variant enzyme. When microbial cells concentration was 30% (w/v), the molar conversion yield and enantiomeric excess of the mRCR variant reached 86.4% and 93.6%, which were increased 36.5% and 15.8% than those of wild-type at a high substrate concentration of 5 g/L. The work will supply a new method for improving chiral alcohol preparation with codon engineered microorganisms.

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

    PubMed

    Wohlin, Åsa

    2015-03-21

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

  5. Kinetics of Stop Codon Recognition by Release Factor 1

    PubMed Central

    Hetrick, Byron; Lee, Kristin; Joseph, Simpson

    2009-01-01

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

  6. Adapt

    NASA Astrophysics Data System (ADS)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  7. Dynamics of dual prism adaptation: relating novel experimental results to a minimalistic neural model.

    PubMed

    Arévalo, Orlando; Bornschlegl, Mona A; Eberhardt, Sven; Ernst, Udo; Pawelzik, Klaus; Fahle, Manfred

    2013-01-01

    In everyday life, humans interact with a dynamic environment often requiring rapid adaptation of visual perception and motor control. In particular, new visuo-motor mappings must be learned while old skills have to be kept, such that after adaptation, subjects may be able to quickly change between two different modes of generating movements ('dual-adaptation'). A fundamental question is how the adaptation schedule determines the acquisition speed of new skills. Given a fixed number of movements in two different environments, will dual-adaptation be faster if switches ('phase changes') between the environments occur more frequently? We investigated the dynamics of dual-adaptation under different training schedules in a virtual pointing experiment. Surprisingly, we found that acquisition speed of dual visuo-motor mappings in a pointing task is largely independent of the number of phase changes. Next, we studied the neuronal mechanisms underlying this result and other key phenomena of dual-adaptation by relating model simulations to experimental data. We propose a simple and yet biologically plausible neural model consisting of a spatial mapping from an input layer to a pointing angle which is subjected to a global gain modulation. Adaptation is performed by reinforcement learning on the model parameters. Despite its simplicity, the model provides a unifying account for a broad range of experimental data: It quantitatively reproduced the learning rates in dual-adaptation experiments for both direct effect, i.e. adaptation to prisms, and aftereffect, i.e. behavior after removal of prisms, and their independence on the number of phase changes. Several other phenomena, e.g. initial pointing errors that are far smaller than the induced optical shift, were also captured. Moreover, the underlying mechanisms, a local adaptation of a spatial mapping and a global adaptation of a gain factor, explained asymmetric spatial transfer and generalization of prism adaptation, as

  8. Adaptive versus maladaptive coping and beliefs and their relation to chronic pain adjustment.

    PubMed

    Tan, Gabriel; Teo, Irene; Anderson, Karen O; Jensen, Mark P

    2011-01-01

    Coping and beliefs are cornerstones to our understanding of adjustment to chronic pain. This study sought to test the hypothesis that maladaptive pain-related coping and beliefs are more strongly related to measures of patient adjustment than are adaptive coping and beliefs. A sample of 106 veterans with mixed chronic pain diagnoses in a multidisciplinary pain treatment program were administered measures of pain beliefs and pain coping, and composite scores were computed to reflect adaptive and maladaptive responses. Correlations between the composite scores and outcomes (pain intensity, pain interference, depression) were examined. Hierarchical multiple regressions were also conducted to estimate the independent contributions of adaptive and maladaptive responses. The maladaptive response composite score was found to be significantly related to pain interference and depression, whereas both adaptive and maladaptive response composite scores were found to be significantly related to pain intensity. The maladaptive response composite showed stronger independent associations with pain interference and depression after controlling for demographic variables, pain intensity, and adaptive responses. Contrary to expectations, only the adaptive response composite showed an independent association with pain intensity. The findings suggest that the relative importance of adaptive versus maladaptive beliefs and coping may differ as a function of the outcome domain in question. The findings support current cognitive-behavioral interventions that focus on reducing the frequency of maladaptive coping responses and beliefs as a way to improve patient functioning.

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

    PubMed

    Trotta, Edoardo

    2016-05-17

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

  10. HER2 codon 655 polymorphism and breast cancer: results from kin-cohort and case-control analyses.

    PubMed

    Millikan, Robert C; Hummer, Amanda J; Wolff, Mary S; Hishida, Asahi; Begg, Colin B

    2005-02-01

    Several published epidemiologic studies show increased breast cancer risk for carriers of the Val-allele at codon 655 of the HER2 gene. We conducted additional analyses using data from three studies, including case-control analyses stratified on age and kin-cohort analyses using relatives of cases and controls. The results provide additional evidence that HER2 codon 655 genotype may predispose to early-onset breast cancer.

  11. Experiences with an adaptive mesh refinement algorithm in numerical relativity.

    NASA Astrophysics Data System (ADS)

    Choptuik, M. W.

    An implementation of the Berger/Oliger mesh refinement algorithm for a model problem in numerical relativity is described. The principles of operation of the method are reviewed and its use in conjunction with leap-frog schemes is considered. The performance of the algorithm is illustrated with results from a study of the Einstein/massless scalar field equations in spherical symmetry.

  12. Therapeutics Based on Stop Codon Readthrough

    PubMed Central

    Keeling, Kim M.; Xue, Xiaojiao; Gunn, Gwen; Bedwell, David M.

    2017-01-01

    Nonsense suppression therapy encompasses approaches aimed at suppressing translation termination at in-frame premature termination codons (PTCs, also known as nonsense mutations) to restore deficient protein function. In this review, we examine the current status of PTC suppression as a therapy for genetic diseases caused by nonsense mutations. We discuss what is currently known about the mechanism of PTC suppression as well as therapeutic approaches under development to suppress PTCs. The approaches considered include readthrough drugs, suppressor tRNAs, PTC pseudouridylation, and inhibition of nonsense-mediated mRNA decay. We also discuss the barriers that currently limit the clinical application of nonsense suppression therapy and suggest how some of these difficulties may be overcome. Finally, we consider how PTC suppression may play a role in the clinical treatment of genetic diseases caused by nonsense mutations. PMID:24773318

  13. Dynamics of Dual Prism Adaptation: Relating Novel Experimental Results to a Minimalistic Neural Model

    PubMed Central

    Arévalo, Orlando; Bornschlegl, Mona A.; Eberhardt, Sven; Ernst, Udo; Pawelzik, Klaus; Fahle, Manfred

    2013-01-01

    In everyday life, humans interact with a dynamic environment often requiring rapid adaptation of visual perception and motor control. In particular, new visuo–motor mappings must be learned while old skills have to be kept, such that after adaptation, subjects may be able to quickly change between two different modes of generating movements (‘dual–adaptation’). A fundamental question is how the adaptation schedule determines the acquisition speed of new skills. Given a fixed number of movements in two different environments, will dual–adaptation be faster if switches (‘phase changes’) between the environments occur more frequently? We investigated the dynamics of dual–adaptation under different training schedules in a virtual pointing experiment. Surprisingly, we found that acquisition speed of dual visuo–motor mappings in a pointing task is largely independent of the number of phase changes. Next, we studied the neuronal mechanisms underlying this result and other key phenomena of dual–adaptation by relating model simulations to experimental data. We propose a simple and yet biologically plausible neural model consisting of a spatial mapping from an input layer to a pointing angle which is subjected to a global gain modulation. Adaptation is performed by reinforcement learning on the model parameters. Despite its simplicity, the model provides a unifying account for a broad range of experimental data: It quantitatively reproduced the learning rates in dual–adaptation experiments for both direct effect, i.e. adaptation to prisms, and aftereffect, i.e. behavior after removal of prisms, and their independence on the number of phase changes. Several other phenomena, e.g. initial pointing errors that are far smaller than the induced optical shift, were also captured. Moreover, the underlying mechanisms, a local adaptation of a spatial mapping and a global adaptation of a gain factor, explained asymmetric spatial transfer and generalization of

  14. A review on auditory space adaptations to altered head-related cues

    PubMed Central

    Mendonça, Catarina

    2014-01-01

    In this article we present a review of current literature on adaptations to altered head-related auditory localization cues. Localization cues can be altered through ear blocks, ear molds, electronic hearing devices, and altered head-related transfer functions (HRTFs). Three main methods have been used to induce auditory space adaptation: sound exposure, training with feedback, and explicit training. Adaptations induced by training, rather than exposure, are consistently faster. Studies on localization with altered head-related cues have reported poor initial localization, but improved accuracy and discriminability with training. Also, studies that displaced the auditory space by altering cue values reported adaptations in perceived source position to compensate for such displacements. Auditory space adaptations can last for a few months even without further contact with the learned cues. In most studies, localization with the subject's own unaltered cues remained intact despite the adaptation to a second set of cues. Generalization is observed from trained to untrained sound source positions, but there is mixed evidence regarding cross-frequency generalization. Multiple brain areas might be involved in auditory space adaptation processes, but the auditory cortex (AC) may play a critical role. Auditory space plasticity may involve context-dependent cue reweighting. PMID:25120422

  15. Adaptation to Climate Change: A Comparative Analysis of Modeling Methods for Heat-Related Mortality.

    PubMed

    Gosling, Simon N; Hondula, David M; Bunker, Aditi; Ibarreta, Dolores; Liu, Junguo; Zhang, Xinxin; Sauerborn, Rainer

    2017-08-16

    Multiple methods are employed for modeling adaptation when projecting the impact of climate change on heat-related mortality. The sensitivity of impacts to each is unknown because they have never been systematically compared. In addition, little is known about the relative sensitivity of impacts to "adaptation uncertainty" (i.e., the inclusion/exclusion of adaptation modeling) relative to using multiple climate models and emissions scenarios. This study had three aims: a) Compare the range in projected impacts that arises from using different adaptation modeling methods; b) compare the range in impacts that arises from adaptation uncertainty with ranges from using multiple climate models and emissions scenarios; c) recommend modeling method(s) to use in future impact assessments. We estimated impacts for 2070-2099 for 14 European cities, applying six different methods for modeling adaptation; we also estimated impacts with five climate models run under two emissions scenarios to explore the relative effects of climate modeling and emissions uncertainty. The range of the difference (percent) in impacts between including and excluding adaptation, irrespective of climate modeling and emissions uncertainty, can be as low as 28% with one method and up to 103% with another (mean across 14 cities). In 13 of 14 cities, the ranges in projected impacts due to adaptation uncertainty are larger than those associated with climate modeling and emissions uncertainty. Researchers should carefully consider how to model adaptation because it is a source of uncertainty that can be greater than the uncertainty in emissions and climate modeling. We recommend absolute threshold shifts and reductions in slope. https://doi.org/10.1289/EHP634.

  16. Two new beta0-thalassemic mutations: a deletion (-CC) at codon 142 or overlapping codons 142-143, and an insertion (+T) at codon 45 or overlapping codons 44-45/45-46 of the beta-globin gene.

    PubMed

    Lacan, Philippe; Aubry, Martine; Couprie, Nicole; Francina, Alain

    2007-01-01

    We report here two new beta(0)-thalassemic mutations. In the first case, a deletion of two nucleotides (-CC) at codon 142 was found in a French Caucasian woman. In the second case, an insertion of a single nucleotide (+T) at codon 45 was found in a Turkish girl. In both cases, no dominant thalassemia-like phenotype was observed.

  17. The relative contributions of global and local acceleration components on speed perception and discriminability following adaptation.

    PubMed

    Hietanen, Markus A

    2015-10-01

    The perception of speed is dependent on the history of previously presented speeds. Adaptation to a given speed regularly results in a reduction of perceived speed and an increase in speed discriminability and in certain circumstances can result in an increase in perceived speed. In order to determine the relative contributions of the local and global speed components on perceived speed, this experiment used expanding dot flow fields with accelerating (global), decelerating (global) and mixed accelerating/decelerating (local) speed patterns. Profound decreases in perceived speed are found when viewing low test speeds after adaptation to high speeds. Small increases in the perceived speed of high test speeds occur following adaptation to low speeds. There were small but significant differences in perceived stimulus speed after adaptation due to different acceleration profiles. No evidence for global modulation of speed discriminability following adaptation was found. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Partial attenuation of Marek's disease virus by manipulation of Di-codon bias

    USDA-ARS?s Scientific Manuscript database

    All species studied to date demonstrate a preference for certain codons over other synonymous codons (codon bias), a preference which is also observed for pairs of codons (di-codon bias). Previous studies using poliovirus and influenza virus as models have demonstrated the ability to cause attenuat...

  19. Protein Synthesis in E. coli: Dependence of Codon-Specific Elongation on tRNA Concentration and Codon Usage.

    PubMed

    Rudorf, Sophia; Lipowsky, Reinhard

    2015-01-01

    To synthesize a protein, a ribosome moves along a messenger RNA (mRNA), reads it codon by codon, and takes up the corresponding ternary complexes which consist of aminoacylated transfer RNAs (aa-tRNAs), elongation factor Tu (EF-Tu), and GTP. During this process of translation elongation, the ribosome proceeds with a codon-specific rate. Here, we present a general theoretical framework to calculate codon-specific elongation rates and error frequencies based on tRNA concentrations and codon usages. Our theory takes three important aspects of in-vivo translation elongation into account. First, non-cognate, near-cognate and cognate ternary complexes compete for the binding sites on the ribosomes. Second, the corresponding binding rates are determined by the concentrations of free ternary complexes, which must be distinguished from the total tRNA concentrations as measured in vivo. Third, for each tRNA species, the difference between total tRNA and ternary complex concentration depends on the codon usages of the corresponding cognate and near-cognate codons. Furthermore, we apply our theory to two alternative pathways for tRNA release from the ribosomal E site and show how the mechanism of tRNA release influences the concentrations of free ternary complexes and thus the codon-specific elongation rates. Using a recently introduced method to determine kinetic rates of in-vivo translation from in-vitro data, we compute elongation rates for all codons in Escherichia coli. We show that for some tRNA species only a few tRNA molecules are part of ternary complexes and, thus, available for the translating ribosomes. In addition, we find that codon-specific elongation rates strongly depend on the overall codon usage in the cell, which could be altered experimentally by overexpression of individual genes.

  20. Codon usage in bacteria: correlation with gene expressivity.

    PubMed Central

    Gouy, M; Gautier, C

    1982-01-01

    The nucleic acid sequence bank now contains over 600 protein coding genes of which 107 are from prokaryotic organisms. Codon frequencies in each new prokaryotic gene are given. Analysis of genetic code usage in the 83 sequenced genes of the Escherichia coli genome (chromosome, transposons and plasmids) is presented, taking into account new data on gene expressivity and regulation as well as iso-tRNA specificity and cellular concentration. The codon composition of each gene is summarized using two indexes: one is based on the differential usage of iso-tRNA species during gene translation, the other on choice between Cytosine and Uracil for third base. A strong relationship between codon composition and mRNA expressivity is confirmed, even for genes transcribed in the same operon. The influence of codon use of peptide elongation rate and protein yield is discussed. Finally, the evolutionary aspect of codon selection in mRNA sequences is studied. PMID:6760125

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

    PubMed

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

    2013-04-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Using social network analysis to evaluate health-related adaptation decision-making in Cambodia.

    PubMed

    Bowen, Kathryn J; Alexander, Damon; Miller, Fiona; Dany, Va

    2014-01-30

    Climate change adaptation in the health sector requires decisions across sectors, levels of government, and organisations. The networks that link these different institutions, and the relationships among people within these networks, are therefore critical influences on the nature of adaptive responses to climate change in the health sector. This study uses social network research to identify key organisational players engaged in developing health-related adaptation activities in Cambodia. It finds that strong partnerships are reported as developing across sectors and different types of organisations in relation to the health risks from climate change. Government ministries are influential organisations, whereas donors, development banks and non-government organisations do not appear to be as influential in the development of adaptation policy in the health sector. Finally, the study highlights the importance of informal partnerships (or 'shadow networks') in the context of climate change adaptation policy and activities. The health governance 'map' in relation to health and climate change adaptation that is developed in this paper is a novel way of identifying organisations that are perceived as key agents in the decision-making process, and it holds substantial benefits for both understanding and intervening in a broad range of climate change-related policy problems where collaboration is paramount for successful outcomes.

  4. Using Social Network Analysis to Evaluate Health-Related Adaptation Decision-Making in Cambodia

    PubMed Central

    Bowen, Kathryn J.; Alexander, Damon; Miller, Fiona; Dany, Va

    2014-01-01

    Climate change adaptation in the health sector requires decisions across sectors, levels of government, and organisations. The networks that link these different institutions, and the relationships among people within these networks, are therefore critical influences on the nature of adaptive responses to climate change in the health sector. This study uses social network research to identify key organisational players engaged in developing health-related adaptation activities in Cambodia. It finds that strong partnerships are reported as developing across sectors and different types of organisations in relation to the health risks from climate change. Government ministries are influential organisations, whereas donors, development banks and non-government organisations do not appear to be as influential in the development of adaptation policy in the health sector. Finally, the study highlights the importance of informal partnerships (or ‘shadow networks’) in the context of climate change adaptation policy and activities. The health governance ‘map’ in relation to health and climate change adaptation that is developed in this paper is a novel way of identifying organisations that are perceived as key agents in the decision-making process, and it holds substantial benefits for both understanding and intervening in a broad range of climate change-related policy problems where collaboration is paramount for successful outcomes. PMID:24487452

  5. Structural basis for stop codon recognition in eukaryotes.

    PubMed

    Brown, Alan; Shao, Sichen; Murray, Jason; Hegde, Ramanujan S; Ramakrishnan, V

    2015-08-27

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

  6. Structural basis for stop codon recognition in eukaryotes

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Hallengren, Erik; Almgren, Peter; Engström, Gunnar; Persson, Margaretha; Melander, Olle

    2015-01-01

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

  8. Positively Selected Codons in Immune-Exposed Loops of the Vaccine Candidate OMP-P1 of Haemophilus influenzae

    PubMed Central

    van Putten, Jos P. M.

    2007-01-01

    The high levels of variation in surface epitopes can be considered as an evolutionary hallmark of immune selection. New computational tools enable analysis of this variation by identifying codons that exhibit high rates of amino acid changes relative to the synonymous substitution rate. In the outer membrane protein P1 of Haemophilus influenzae, a vaccine candidate for nontypeable strains, we identified four codons with this attribute in domains that did not correspond to known or assumed B- and T-cell epitopes of OMP-P1. These codons flank hypervariable domains and do not appear to be false positives as judged from parsimony and maximum likelihood analyses. Some closely spaced positively selected codons have been previously considered part of a transmembrane domain, which would render this region unsuited for inclusion in a vaccine. Secondary structure analysis, three-dimensional structural database searches, and homology modeling using FadL of E. coli as a structural homologue, however, revealed that all positively selected codons are located in or near extracellular looping domains. The spacing and level of diversity of these positively selected and exposed codons in OMP-P1 suggest that vaccine targets based on these and conserved flanking residues may provide broad coverage in H. influenzae. Electronic Supplementary Material The online version of this article (doi:10.1007/s00239-006-0021-2) contains supplementary material, which is available to authorized users. PMID:17479342

  9. Does Stress-Related Growth Really Matter for Adolescents' Day-to-Day Adaptive Functioning?

    ERIC Educational Resources Information Center

    Mansfield, Cade D.; Diamond, Lisa M.

    2017-01-01

    Adolescent stress-related growth refers to enhancement in an adolescent's cognitive-affective or social resources as a result of experiencing stressors. We tested whether adolescents reporting high levels of stress-related growth showed superior adaptation outcomes on a day-to-day basis. Participants (n = 91; females = 46, age = 14) completed a…

  10. Premotor inhibitory neurons carry signals related to saccade adaptation in the monkey.

    PubMed

    Kojima, Yoshiko; Iwamoto, Yoshiki; Robinson, Farrel R; Noto, Christopher T; Yoshida, Kaoru

    2008-01-01

    Cerebellar output changes during motor learning. How these changes cause alterations of motoneuron activity and movement remains an unresolved question for voluntary movements. To answer this question, we examined premotor neurons for saccadic eye movement. Previous studies indicate that cells in the fastigial oculomotor region (FOR) within the cerebellar nuclei on one side exhibit a gradual increase in their saccade-related discharge as the amplitude of ipsiversive saccades adaptively decreases. This change in FOR activity could cause the adaptive change in saccade amplitude because neurons in the FOR project directly to the brain stem region containing premotor burst neurons (BNs). To test this possibility, we recorded the activity of saccade-related burst neurons in the area that houses premotor inhibitory burst neurons (IBNs) and examined their discharge during amplitude-reducing adaptation elicited by intrasaccadic target steps. We specifically analyzed their activity for off-direction (contraversive) saccades, in which the IBN activity would increase to reduce saccade size. Before adaptation, 29 of 42 BNs examined discharged, at least occasionally, for contraversive saccades. As the amplitude of contraversive saccades decreased adaptively, half of BNs with off-direction spike activity showed an increase in the number of spikes (14/29) or an earlier occurrence of spikes (7/14). BNs that were silent during off-direction saccades before adaptation remained silent after adaptation. These results indicate that the changes in the off-direction activity of BNs are closely related to adaptive changes in saccade size and are appropriate to cause these changes.

  11. The Relation Between Intellectual Functioning and Adaptive Behavior in the Diagnosis of Intellectual Disability.

    PubMed

    Tassé, Marc J; Luckasson, Ruth; Schalock, Robert L

    2016-12-01

    Intellectual disability originates during the developmental period and is characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. In this article, we present a brief history of the diagnostic criteria of intellectual disability for both the DSM-5 and AAIDD. The article also (a) provides an update of the understanding of adaptive behavior, (b) dispels two thinking errors regarding mistaken temporal or causal link between intellectual functioning and adaptive behavior, (c) explains that there is a strong correlational, but no causative, relation between intellectual functioning and adaptive behavior, and (d) asserts that once a question of determining intellectual disability is raised, both intellectual functioning and adaptive behavior are assessed and considered jointly and weighed equally in the diagnosis of intellectual disability. We discuss the problems created by an inaccurate statement that appears in the DSM-5 regarding a causal link between deficits in intellectual functioning and adaptive behavior and propose an immediate revision to remove this erroneous and confounding statement.

  12. Efficient translation initiation dictates codon usage at gene start

    PubMed Central

    Bentele, Kajetan; Saffert, Paul; Rauscher, Robert; Ignatova, Zoya; Blüthgen, Nils

    2013-01-01

    The genetic code is degenerate; thus, protein evolution does not uniquely determine the coding sequence. One of the puzzles in evolutionary genetics is therefore to uncover evolutionary driving forces that result in specific codon choice. In many bacteria, the first 5–10 codons of protein-coding genes are often codons that are less frequently used in the rest of the genome, an effect that has been argued to arise from selection for slowed early elongation to reduce ribosome traffic jams. However, genome analysis across many species has demonstrated that the region shows reduced mRNA folding consistent with pressure for efficient translation initiation. This raises the possibility that unusual codon usage is a side effect of selection for reduced mRNA structure. Here we discriminate between these two competing hypotheses, and show that in bacteria selection favours codons that reduce mRNA folding around the translation start, regardless of whether these codons are frequent or rare. Experiments confirm that primarily mRNA structure, and not codon usage, at the beginning of genes determines the translation rate. PMID:23774758

  13. Determinants of Initiation Codon Selection during Translation in Mammalian Cells

    PubMed Central

    Matsuda, Daiki; Mauro, Vincent P.

    2010-01-01

    Factors affecting translation of mRNA contribute to the complexity of eukaryotic proteomes. In some cases, translation of a particular mRNA can generate multiple proteins. However, the factors that determine whether ribosomes initiate translation from the first AUG codon in the transcript, from a downstream codon, or from multiple sites are not completely understood. Various mRNA properties, including AUG codon-accessibility and 5′ leader length have been proposed as potential determinants that affect where ribosomes initiate translation. To explore this issue, we performed studies using synthetic mRNAs with two in-frame AUG codons−both in excellent context. Open reading frames initiating at AUG1 and AUG2 encode large and small isoforms of a reporter protein, respectively. Translation of such an mRNA in COS-7 cells was shown to be 5′ cap-dependent and to occur efficiently from both AUG codons. AUG codon-accessibility was modified by using two different elements: an antisense locked nucleic acid oligonucleotide and an exon-junction complex. When either element was used to mask AUG1, the ratio of the proteins synthesized changed, favoring the smaller (AUG2-initiated) protein. In addition, we observed that increased leader length by itself changed the ratio of the proteins and favored initiation at AUG1. These observations demonstrate that initiation codon selection is affected by various factors, including AUG codon-accessibility and 5′ leader length, and is not necessarily determined by the order of AUG codons (5′→3′). The modulation of AUG codon accessibility may provide a powerful means of translation regulation in eukaryotic cells. PMID:21124832

  14. Codon engineering for improved antibody expression in mammalian cells.

    PubMed

    Carton, Jill M; Sauerwald, Tina; Hawley-Nelson, Pam; Morse, Barry; Peffer, Nancy; Beck, Heena; Lu, Jin; Cotty, Adam; Amegadzie, Bernard; Sweet, Ray

    2007-10-01

    While well established in bacterial hosts, the effect of coding sequence variation on protein expression in mammalian systems is poorly characterized outside of viral proteins or proteins from distant phylogenetic families. The potential impact is substantial given the extensive use of mammalian expression systems in research and manufacturing of protein biotherapeutics. We are studying the effect of codon engineering on expression of recombinant antibodies with an emphasis on developing manufacturing cell lines. CNTO 888, a human mAb specific for human MCP-1, was obtained by antibody phage display in collaboration with MorphoSys AG. The isolated DNA sequence of the antibody was biased towards bacterial codons, reflecting the engineering of the Fab library for phage display expression in Escherichia coli. We compared the expression of CNTO 888 containing the parental V-region sequences with two engineered coding variants. In the native codon exchanged (NCE) variant, the V-region codons were replaced with those used in naturally derived human antibody genes. In the human codon optimized (HCO) variant the V-region codons were those used at the highest frequency based on a human codon usage table. The antibody expression levels from stable transfections in mammalian host cells were measured. The HCO codon variant of CNTO 888 yielded the highest expressing cell lines and the highest average expression for the screened populations. This had a significant positive effect on the process to generate a CNTO 888 production cell line and indicates the potential to improve antibody expression in mammalian expression systems by codon engineering.

  15. DNA G+C content of the third codon position and codon usage biases of human genes.

    PubMed

    Sueoka, N; Kawanishi, Y

    2000-12-30

    The human genome, as in other eukaryotes, has a wide heterogeneity in the DNA base composition. The evolutionary basis for this heterogeneity has been unknown. A previous study of the human genome (846 genes analyzed) has shown that, in the major range of the G+C content in the third codon position (0.25-0.75), biases from the Parity Rule 2 (PR2) among the synonymous codons of the four-codon amino acids are similar except in the highest G+C range (Sueoka, N., 1999. Translation-coupled violation of Parity Rule 2 in human genes is not the cause of heterogeneity of the DNA G+C content of third codon position. Gene 238, 53-58.). PR2 is an intra-strand rule where A=T and G=C are expected when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates). In this study, 14,026 human genes were analyzed. In addition, the third codon positions of two-codon amino acids were analyzed. New results show the following: (a) The G+C contents of the third codon position of human genes are scattered in the G+C range of 0.22-0.96 in the third codon position. (b) The PR2 biases are similar in the range of 0.25-0.75, whereas, in the high G+C range (0.75-0.96; 13% of the genes), the PR2-bias fingerprints are different from those of the major range. (c) Unlike the PR2 biases, the G+C contents of the third codon position for both four-codon and two-codon amino acids are all correlated almost perfectly with the G+C content of the third codon position over the total G+C ranges. These results support the notion that the directional mutation pressure, rather than the directional selection pressure, is mainly responsible for the heterogeneity of the G+C content of the third codon position.

  16. Effects of codon optimization on the mRNA levels of heterologous genes in filamentous fungi.

    PubMed

    Tanaka, Mizuki; Tokuoka, Masafumi; Gomi, Katsuya

    2014-05-01

    Filamentous fungi, particularly Aspergillus species, have recently attracted attention as host organisms for recombinant protein production. Because the secretory yields of heterologous proteins are generally low compared with those of homologous proteins or proteins from closely related fungal species, several strategies to produce substantial amounts of recombinant proteins have been conducted. Codon optimization is a powerful tool for improving the production levels of heterologous proteins. Although codon optimization is generally believed to improve the translation efficiency of heterologous genes without affecting their mRNA levels, several studies have indicated that codon optimization causes an increase in the steady-state mRNA levels of heterologous genes in filamentous fungi. However, the mechanism that determines the low mRNA levels when native heterologous genes are expressed was poorly understood. We recently showed that the transcripts of heterologous genes are polyadenylated prematurely within the coding region and that the heterologous gene transcripts can be stabilized significantly by codon optimization, which is probably attributable to the prevention of premature polyadenylation in Aspergillus oryzae. In this review, we describe the detailed mechanism of premature polyadenylation and the rapid degradation of mRNA transcripts derived from heterologous genes in filamentous fungi.

  17. Effective population size does not predict codon usage bias in mammals

    PubMed Central

    Kessler, Michael D; Dean, Matthew D

    2014-01-01

    Synonymous codons are not used at equal frequency throughout the genome, a phenomenon termed codon usage bias (CUB). It is often assumed that interspecific variation in the intensity of CUB is related to species differences in effective population sizes (Ne), with selection on CUB operating less efficiently in species with small Ne. Here, we specifically ask whether variation in Ne predicts differences in CUB in mammals and report two main findings. First, across 41 mammalian genomes, CUB was not correlated with two indirect proxies of Ne (body mass and generation time), even though there was statistically significant evidence of selection shaping CUB across all species. Interestingly, autosomal genes showed higher codon usage bias compared to X-linked genes, and high-recombination genes showed higher codon usage bias compared to low recombination genes, suggesting intraspecific variation in Ne predicts variation in CUB. Second, across six mammalian species with genetic estimates of Ne (human, chimpanzee, rabbit, and three mouse species: Mus musculus, M. domesticus, and M. castaneus), Ne and CUB were weakly and inconsistently correlated. At least in mammals, interspecific divergence in Ne does not strongly predict variation in CUB. One hypothesis is that each species responds to a unique distribution of selection coefficients, confounding any straightforward link between Ne and CUB. PMID:25505518

  18. Conservation of CFTR codon frequency through primates suggests synonymous mutations could have a functional effect.

    PubMed

    Pizzo, Lucilla; Iriarte, Andrés; Alvarez-Valin, Fernando; Marín, Mónica

    2015-05-01

    Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease.

  19. Electrophysiological correlates related to the conflict adaptation effect in an emotional conflict task.

    PubMed

    Xue, Song; Ren, Guofang; Kong, Xia; Liu, Jia; Qiu, Jiang

    2015-01-01

    Previous studies have provided some evidence of the neural basis of the emotional conflict adaptation effect. However, the neural time-course is largely unknown. Therefore, a face-word Stroop task was used in the present study to explore the neural dynamics of the emotional conflict control effect, using event-related potentials (ERPs). The behavioral data showed a robust emotional conflict adaptation effect, and there was an interaction between previous trials and current trials for RT. There were two ERP components (N450 and conflict SP) that might be related to trial congruency. The N450 results showed both a main effect of current trial congruency and an interaction between previous trials and current trials, which might be related to successful conflict adaptation. The SP results only showed the main effect of current trial congruency, which might be associated with post-response monitoring. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. A thermodynamic theory of codon bias in viral genes.

    PubMed

    Rowe, G W; Trainor, L E

    1983-03-21

    The relationship between degeneracy in the genetic code and the occurrence of a strong codon bias is examined, with particular reference to a group of viral genomes. The present paper shows how codon bias may have been imposed by thermodynamic considerations at the time the primitive DNA first formed in the primordial soup. Using a four-state Ising-like model with stacking interactions between successive base pairs, we show how primeval periodic DNA polymers could have arisen the remnants of which are still observed in codon biases today.

  1. [Adaptive moving averaging based estimation of single event-related potentials].

    PubMed

    Qi, C; Liang, D; Jiang, X

    2001-03-01

    Event-related potentials (ERP) is pertinent to medical research and clinical diagnosis. Estimation of single event-related potentials (sERP) is the objective of ERP processing. A new technique, adaptive moving averaging based method for estimation of sERP, is presented. After analysis of the properties of background noise by crossing zero, the window length of moving averaging is adaptively set according to the maximum width of the impulse noise for each recorded raw data. The experiments are made with real recorded data and the results demonstrate that the performance of sERP estimation is excellent. So the method proposed is suitable to sERP processing.

  2. How tRNAs dictate nuclear codon reassignments: Only a few can capture non-cognate codons.

    PubMed

    Kollmar, Martin; Mühlhausen, Stefanie

    2017-03-04

    mRNA decoding by tRNAs and tRNA charging by aminoacyl-tRNA synthetases are biochemically separated processes that nevertheless in general involve the same nucleotides. The combination of charging and decoding determines the genetic code. Codon reassignment happens when a differently charged tRNA replaces a former cognate tRNA. The recent discovery of the polyphyly of the yeast CUG sense codon reassignment challenged previous mechanistic considerations and led to the proposal of the so-called tRNA loss driven codon reassignment hypothesis. Accordingly, codon capture is caused by loss of a tRNA or by mutations in the translation termination factor, subsequent reduction of the codon frequency through reduced translation fidelity and final appearance of a new cognate tRNA. Critical for codon capture are sequence and structure of the new tRNA, which must be compatible with recognition regions of aminoacyl-tRNA synthetases. The proposed hypothesis applies to all reported nuclear and organellar codon reassignments.

  3. Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer.

    PubMed

    Almeida, B C; Kleine, J P F O; Camargo-Kosugi, C M; Lisboa, M R; França, C N; França, J P; Silva, I D C G

    2016-02-22

    The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.

  4. UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota

    PubMed Central

    Campbell, James H.; O’Donoghue, Patrick; Campbell, Alisha G.; Schwientek, Patrick; Sczyrba, Alexander; Woyke, Tanja; Söll, Dieter; Podar, Mircea

    2013-01-01

    The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNAGlyUCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNAGlyUCA with glycine in vitro with similar activity compared with normal tRNAGlyUCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNAGlyUCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota. PMID:23509275

  5. UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.

    PubMed

    Campbell, James H; O'Donoghue, Patrick; Campbell, Alisha G; Schwientek, Patrick; Sczyrba, Alexander; Woyke, Tanja; Söll, Dieter; Podar, Mircea

    2013-04-02

    The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.

  6. Adaptive genetic changes related to haemoglobin concentration in native high-altitude Tibetans.

    PubMed

    Simonson, T S; Huff, C D; Witherspoon, D J; Prchal, J T; Jorde, L B

    2015-11-01

    What is the topic of this review? Tibetans have genetic adaptations that are hypothesized to underlie the distinct set of traits they exhibit at altitude. What advances does it highlight? Several adaptive signatures in the same genomic regions have been identified among Tibetan populations resident throughout the Qinghai-Tibetan Plateau. Many highland Tibetans exhibit a haemoglobin concentration within the range expected at sea level, and this trait is associated with putatively adaptive regions harbouring the hypoxia-inducible factor pathway genes EGLN1, EPAS1 and PPARA. Precise functional variants at adaptive loci and relationships to physiological traits, beyond haemoglobin concentration, are currently being examined in this population. Some native Tibetan, Andean and Ethiopian populations have lived at altitudes ranging from 3000 to >4000 m above sea level for hundreds of generations and exhibit distinct combinations of traits at altitude. It was long hypothesized that genetic factors contribute to adaptive differences in these populations, and recent advances in genomics provide evidence that some of the strongest signatures of positive selection in humans are those identified in Tibetans. Many of the top adaptive genomic regions highlighted thus far harbour genes related to hypoxia sensing and response. Putatively adaptive copies of three hypoxia-inducible factor pathway genes, EPAS1, EGLN1 and PPARA, are associated with sea-level range, rather than elevated, haemoglobin concentration observed in many Tibetans at high altitude, and recent studies provide insight into some of the precise adaptive variants, timing of adaptive events and functional roles. While several studies in highland Tibetans have converged on a few hypoxia-inducible factor pathway genes, additional candidates have been reported in independent studies of Tibetans located throughout the Qinghai-Tibetan Plateau. Various aspects of adaptive significance have yet to be identified, integrated

  7. Bicluster pattern of codon context usages between flavivirus and vector mosquito Aedes aegypti: relevance to infection and transcriptional response of mosquito genes.

    PubMed

    Behura, Susanta K; Severson, David W

    2014-10-01

    The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in most of the subtropical and tropical countries. Besides DENV, yellow fever virus (YFV) is also transmitted by A. aegypti. Susceptibility of A. aegypti to West Nile virus (WNV) has also been confirmed. Although studies have indicated correlation of codon bias between flaviviridae and their animal/insect hosts, it is not clear if codon sequences have any relation to susceptibility of A. aegypti to DENV, YFV and WNV. In the current study, usages of codon context sequences (codon pairs for neighboring amino acids) of the vector (A. aegypti) genome as well as the flaviviral genomes are investigated. We used bioinformatics methods to quantify codon context bias in a genome-wide manner of A. aegypti as well as DENV, WNV and YFV sequences. Mutual information statistics was applied to perform bicluster analysis of codon context bias between vector and flaviviral sequences. Functional relevance of the bicluster pattern was inferred from published microarray data. Our study shows that codon context bias of DENV, WNV and YFV sequences varies in a bicluster manner with that of specific sets of genes of A. aegypti. Many of these mosquito genes are known to be differentially expressed in response to flaviviral infection suggesting that codon context sequences of A. aegypti and the flaviviruses may play a role in the susceptible interaction between flaviviruses and this mosquito. The bias in usages of codon context sequences likely has a functional association with susceptibility of A. aegypti to flaviviral infection. The results from this study will allow us to conduct hypothesis-driven tests to examine the role of codon context bias in evolution of vector-virus interactions at the molecular level.

  8. Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9

    PubMed Central

    Newman, Zachary R.; Young, Janet M.; Ingolia, Nicholas T.; Barton, Gregory M.

    2016-01-01

    The innate immune system detects diverse microbial species with a limited repertoire of immune receptors that recognize nucleic acids. The cost of this immune surveillance strategy is the potential for inappropriate recognition of self-derived nucleic acids and subsequent autoimmune disease. The relative expression of two closely related receptors, Toll-like receptor (TLR) 7 and TLR9, is balanced to allow recognition of microbial nucleic acids while limiting recognition of self-derived nucleic acids. Situations that tilt this balance toward TLR7 promote inappropriate responses, including autoimmunity; therefore, tight control of expression is critical for proper homeostasis. Here we report that differences in codon bias limit TLR7 expression relative to TLR9. Codon optimization of Tlr7 increases protein levels as well as responses to ligands, but, unexpectedly, these changes only modestly affect translation. Instead, we find that much of the benefit attributed to codon optimization is actually the result of enhanced transcription. Our findings, together with other recent examples, challenge the dogma that codon optimization primarily increases translation. We propose that suboptimal codon bias, which correlates with low guanine-cytosine (GC) content, limits transcription of certain genes. This mechanism may establish low levels of proteins whose overexpression leads to particularly deleterious effects, such as TLR7. PMID:26903634

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-12-01

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

  11. The Effects of Reflective Activities on Skill Adaptation in a Work-Related Instrumental Learning Setting

    ERIC Educational Resources Information Center

    Roessger, Kevin M.

    2014-01-01

    In work-related instrumental learning contexts, the role of reflective activities is unclear. Kolb's experiential learning theory and Mezirow's transformative learning theory predict skill adaptation as an outcome. This prediction was tested by manipulating reflective activities and assessing participants' response and error rates during novel…

  12. The Emotions of Socialization-Related Learning: Understanding Workplace Adaptation as a Learning Process.

    ERIC Educational Resources Information Center

    Reio, Thomas G., Jr.

    The influence of selected discrete emotions on socialization-related learning and perception of workplace adaptation was examined in an exploratory study. Data were collected from 233 service workers in 4 small and medium-sized companies in metropolitan Washington, D.C. The sample members' average age was 32.5 years, and the sample's racial makeup…

  13. Adaptive Memory: Young Children Show Enhanced Retention of Fitness-Related Information

    ERIC Educational Resources Information Center

    Aslan, Alp; Bauml, Karl-Heinz T.

    2012-01-01

    Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on…

  14. Contributions of the Relational Context to Career Adaptability among Urban Adolescents

    ERIC Educational Resources Information Center

    Kenny, Maureen E.; Bledsoe, Meredith

    2005-01-01

    The combined and unique contributions of four relational factors to four dimensions of career adaptability were examined for a sample of 322 urban high school students. When all variables were considered simultaneously, canonical analysis revealed that support from family, teachers, and close friends, and peer beliefs about school contributed…

  15. Adapting to Changing Memory Retrieval Demands: Evidence from Event-Related Potentials

    ERIC Educational Resources Information Center

    Benoit, Roland G.; Werkle-Bergner, Markus; Mecklinger, Axel; Kray, Jutta

    2009-01-01

    This study investigated preparatory processes involved in adapting to changing episodic memory retrieval demands. Event-related potentials (ERPs) were recorded while participants performed a general old/new recognition task and a specific task that also required retrieval of perceptual details. The relevant task remained either constant or changed…

  16. Relating adaptive genetic traits to climate for Sandberg bluegrass from the intermountain western United States

    Treesearch

    Richard C. Johnson; Matthew E. Horning; Erin Espeland; Ken Vance-Borland

    2015-01-01

    Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source population climate. Common gardens were established at two intermountain west sites with progeny from two maternal parents from each of 130 wild populations. Data were...

  17. Critically Adaptive Pedagogical Relations: The Relevance for Educational Policy and Practice

    ERIC Educational Resources Information Center

    Griffiths, Morwenna

    2013-01-01

    In this article Morwenna Griffiths argues that teacher education policies should be predicated on a proper and full understanding of pedagogical relations as contingent, responsive, and adaptive over the course of a career. Griffiths uses the example of the recent report on teacher education in Scotland, by Graham Donaldson, to argue that for all…

  18. Relating adaptive genetic traits to climate for Sandberg bluegrass from the intermountain western United States

    USDA-ARS?s Scientific Manuscript database

    Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source climate. Common gardens were established at two intermountain west sites with progeny from two m...

  19. Bibliography of Selected Literature in the 1970s Related to Crises, Family Stress, Coping and Adaptation.

    ERIC Educational Resources Information Center

    Chesser, Barbara

    This bibliography of literature from the 1970s related to crises, family stress, coping, and adaptation contains references of particular interest to professionals in the areas of counseling, education, and family social, psychological and health services. The bibliography is divided into 26 categories; references are classified according to major…

  20. Critically Adaptive Pedagogical Relations: The Relevance for Educational Policy and Practice

    ERIC Educational Resources Information Center

    Griffiths, Morwenna

    2013-01-01

    In this article Morwenna Griffiths argues that teacher education policies should be predicated on a proper and full understanding of pedagogical relations as contingent, responsive, and adaptive over the course of a career. Griffiths uses the example of the recent report on teacher education in Scotland, by Graham Donaldson, to argue that for all…

  1. Adaptive Memory: Young Children Show Enhanced Retention of Fitness-Related Information

    ERIC Educational Resources Information Center

    Aslan, Alp; Bauml, Karl-Heinz T.

    2012-01-01

    Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on…

  2. Adaptation of orientation vectors of otolith-related central vestibular neurons to gravity.

    PubMed

    Eron, Julia N; Cohen, Bernard; Raphan, Theodore; Yakushin, Sergei B

    2008-09-01

    Behavioral experiments indicate that central pathways that process otolith-ocular and perceptual information have adaptive capabilities. Because polarization vectors of otolith afferents are directly related to the electro-mechanical properties of the hair cell bundle, it is unlikely that they change their direction of excitation. This indicates that the adaptation must take place in central pathways. Here we demonstrate for the first time that otolith polarization vectors of canal-otolith convergent neurons in the vestibular nuclei have adaptive capability. A total of 10 vestibular-only and vestibular-plus-saccade neurons were recorded extracellularly in two monkeys before and after they were in side-down positions for 2 h. The spatial characteristics of the otolith input were determined from the response vector orientation (RVO), which is the projection of the otolith polarization vector, onto the head horizontal plane. The RVOs had no specific orientation before animals were in side-down positions but moved toward the gravitational axis after the animals were tilted for extended periods. Vector reorientations varied from 0 to 109 degrees and were linearly related to the original deviation of the RVOs from gravity in the position of adaptation. Such reorientation of central polarization vectors could provide the basis for changes in perception and eye movements related to prolonged head tilts relative to gravity or in microgravity.

  3. Adaptation of Orientation Vectors of Otolith-Related Central Vestibular Neurons to Gravity

    PubMed Central

    Eron, Julia N.; Cohen, Bernard; Raphan, Theodore; Yakushin, Sergei B.

    2008-01-01

    Behavioral experiments indicate that central pathways that process otolith-ocular and perceptual information have adaptive capabilities. Because polarization vectors of otolith afferents are directly related to the electro-mechanical properties of the hair cell bundle, it is unlikely that they change their direction of excitation. This indicates that the adaptation must take place in central pathways. Here we demonstrate for the first time that otolith polarization vectors of canal-otolith convergent neurons in the vestibular nuclei have adaptive capability. A total of 10 vestibular-only and vestibular-plus-saccade neurons were recorded extracellularly in two monkeys before and after they were in side-down positions for 2 h. The spatial characteristics of the otolith input were determined from the response vector orientation (RVO), which is the projection of the otolith polarization vector, onto the head horizontal plane. The RVOs had no specific orientation before animals were in side-down positions but moved toward the gravitational axis after the animals were tilted for extended periods. Vector reorientations varied from 0 to 109° and were linearly related to the original deviation of the RVOs from gravity in the position of adaptation. Such reorientation of central polarization vectors could provide the basis for changes in perception and eye movements related to prolonged head tilts relative to gravity or in microgravity. PMID:18497367

  4. Linguistic and cultural adaptation needs of Mexican American nursing students related to multiple-choice tests.

    PubMed

    Lujan, Josefina

    2008-07-01

    Hispanic nurses represent less than 2% of the current U.S. nursing workforce, despite that approximately 14% of the nation's population is Hispanic. There is an urgent need to correct the gross underrepresentation of Mexican Americans, the largest subgroup among Hispanics, in the U.S. nursing workforce to provide culturally concordant care. One solution is to increase the academic success of Mexican American nursing students with English as a second language through improved linguistic and cultural adaptation to multiple-choice tests. This article will discuss these students' linguistic and cultural adaptation needs related to multiple-choice tests and will also present several intervention strategies and a case study.

  5. Introgression of Novel Traits from a Wild Wheat Relative Improves Drought Adaptation in Wheat1[W

    PubMed Central

    Placido, Dante F.; Campbell, Malachy T.; Folsom, Jing J.; Cui, Xinping; Kruger, Greg R.; Baenziger, P. Stephen; Walia, Harkamal

    2013-01-01

    Root architecture traits are an important component for improving water stress adaptation. However, selection for aboveground traits under favorable environments in modern cultivars may have led to an inadvertent loss of genes and novel alleles beneficial for adapting to environments with limited water. In this study, we elucidate the physiological and molecular consequences of introgressing an alien chromosome segment (7DL) from a wild wheat relative species (Agropyron elongatum) into cultivated wheat (Triticum aestivum). The wheat translocation line had improved water stress adaptation and higher root and shoot biomass compared with the control genotypes, which showed significant drops in root and shoot biomass during stress. Enhanced access to water due to higher root biomass enabled the translocation line to maintain more favorable gas-exchange and carbon assimilation levels relative to the wild-type wheat genotypes during water stress. Transcriptome analysis identified candidate genes associated with root development. Two of these candidate genes mapped to the site of translocation on chromosome 7DL based on single-feature polymorphism analysis. A brassinosteroid signaling pathway was predicted to be involved in the novel root responses observed in the A. elongatum translocation line, based on the coexpression-based gene network generated by seeding the network with the candidate genes. We present an effective and highly integrated approach that combines root phenotyping, whole-plant physiology, and functional genomics to discover novel root traits and the underlying genes from a wild related species to improve drought adaptation in cultivated wheat. PMID:23426195

  6. Introgression of novel traits from a wild wheat relative improves drought adaptation in wheat.

    PubMed

    Placido, Dante F; Campbell, Malachy T; Folsom, Jing J; Cui, Xinping; Kruger, Greg R; Baenziger, P Stephen; Walia, Harkamal

    2013-04-01

    Root architecture traits are an important component for improving water stress adaptation. However, selection for aboveground traits under favorable environments in modern cultivars may have led to an inadvertent loss of genes and novel alleles beneficial for adapting to environments with limited water. In this study, we elucidate the physiological and molecular consequences of introgressing an alien chromosome segment (7DL) from a wild wheat relative species (Agropyron elongatum) into cultivated wheat (Triticum aestivum). The wheat translocation line had improved water stress adaptation and higher root and shoot biomass compared with the control genotypes, which showed significant drops in root and shoot biomass during stress. Enhanced access to water due to higher root biomass enabled the translocation line to maintain more favorable gas-exchange and carbon assimilation levels relative to the wild-type wheat genotypes during water stress. Transcriptome analysis identified candidate genes associated with root development. Two of these candidate genes mapped to the site of translocation on chromosome 7DL based on single-feature polymorphism analysis. A brassinosteroid signaling pathway was predicted to be involved in the novel root responses observed in the A. elongatum translocation line, based on the coexpression-based gene network generated by seeding the network with the candidate genes. We present an effective and highly integrated approach that combines root phenotyping, whole-plant physiology, and functional genomics to discover novel root traits and the underlying genes from a wild related species to improve drought adaptation in cultivated wheat.

  7. Data and knowledge gaps in glacier, snow and related runoff research - A climate change adaptation perspective

    NASA Astrophysics Data System (ADS)

    Salzmann, Nadine; Huggel, Christian; Rohrer, Mario; Stoffel, Markus

    2014-10-01

    Glacier and snow cover changes with related impacts on melt runoff can seriously affect human societies which are depending on fresh water from cryospheric sources. Observed trends and projected future evolutions of climatic and cryospheric variables clearly show the need to adapt to these changes. Accordingly, the topics addressed herein have been put on the agendas of many larger funding agencies. This article provides a brief overview on major ongoing activities on glacier, snow and related runoff research in order to then analyze data gaps and research needs from a climate change adaptation perspective. Major data needs are identified with respect to the spatial and temporal coverage of local-scale data and related needs for (data) services that distribute and maintain these data sets. Moreover, clear research needs are also recognized at the local scale where process knowledge needs to be improved (e.g., the influence of albedo on snow and ice or debris cover on glaciers) in order to derive plausible climate change impacts assessments. The paper then discusses directions on how to move forward to better serve the practical needs for climate change adaptation planning. In the future, substantial support by large funding agencies might be key for capacity building in target regions of climate change adaptation programs, for longer-term and more sustainable commitments, and for the development of approaches, which aim at assessing the transferability of data, techniques, and tools.

  8. NECTAR: a database of codon-centric missense variant annotations.

    PubMed

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

    2014-01-01

    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.

  9. G to A transitions and G to T transversions in codon 12 of the Ki-ras oncogene isolated from mouse lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related DNA methylating and pyridyloxobutylating agents.

    PubMed

    Ronai, Z A; Gradia, S; Peterson, L A; Hecht, S S

    1993-11-01

    Lung tumors were induced in A/J mice by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the related compounds acetoxymethylmethylnitrosamine (AMMN) and 4-acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc). NNK both methylates and pyridyloxobutylates DNA while AMMN and NNKOAc only methylate or pyridyloxobutylate DNA, respectively. The lung tumors were analyzed for mutations in the Ki-ras oncogene by PCR amplification followed by either restriction fragment length polymorphism, hybridization, or sequencing procedures. NNK induced GGT to GAT mutations in codon 12 (26 of 28 samples analyzed). AMMN induced GGT to GAT mutations in 18 of 18 samples. In contrast, NNKOAc induced a variety of changes including GGT to GAT (8/21), GGT to TGT (5/21) and GGT to GTT (4/21) mutations. These results demonstrate that DNA methylation causes mainly G to A transitions in the Ki-ras gene of A/J mouse lung tumors, consistent with previous results and a role for O6-methyl-guanine, while DNA pyridyloxobutylation induces G to A transitions as well as G to T transversions, perhaps due to the steric bulk of the adducts which are formed. The results are discussed with respect to mutations observed in rodent and human lung tumors.

  10. Orientation adaptation of eye movement–related vestibular neurons due to prolonged head tilt

    PubMed Central

    Kolesnikova, Olga V.; Raphan, Theodore; Cohen, Bernard; Yakushin, Sergei B.

    2012-01-01

    Sixteen neurons, including vestibular-only (VO), eye–head velocity (EHV), and position-vestibular-pause (PVP) neurons sensitive to head tilt were recorded in the rostromedial and in superior vestibular nuclei. Projection of the otolith polarization vector to the horizontal plane (response vector orientation [RVO]) was determined before and after prolonged head orientation in side-down position. The RVO of VO neurons shifted toward alignment with the axis of gravity when the head was in the position of adaptation. PVP neurons had similar changes in RVO. There were also changes in RVO in some EHV neurons, but generally in directions not related to gravity. Modeling studies have suggested that the tendency to align RVOs with gravity leads to tuning of gravity-dependent angular vestibular ocular reflex (aVOR) gain changes to the position of adaptation. Thus, coding of orientation in PVP neurons would contribute significantly to the gravity-dependent adaptation of the aVOR. PMID:21950996

  11. Vowel generalization and its relation to adaptation during perturbations of auditory feedback.

    PubMed

    Reilly, Kevin J; Pettibone, Chelsea

    2017-08-23

    Repeated perturbations of auditory feedback during vowel production elicit changes not only in the production of the perturbed vowel (adaptation) but also in the production of nearby vowels that were not perturbed (generalization). The finding that adaptation generalizes to other, non-perturbed vowels suggest that sensorimotor representations for vowels are not independent; instead the goals for producing any one vowel may depend in part on the goals for other vowels. The present study investigated the dependence or independence of vowel representations by evaluating adaptation and generalization in two groups of speakers exposed to auditory perturbations of their first formant (F1) during different vowels. The speakers in both groups who adapted to the perturbation exhibited generalization in two non-perturbed vowels that were produced under masking noise. Correlation testing was performed to evaluate the relations between adaptation and generalization as well as between the generalization in the two non-perturbed vowels. These tests identified significant coupling between the F1 changes of adjacent vowels but not non-adjacent vowels. The pattern of correlation findings indicates that generalization was due in part to feedforward representations that are partly shared across adjacent vowels, possibly to maintain their acoustic contrast. Copyright © 2016, Journal of Neurophysiology.

  12. Acting Bicultural versus Feeling Bicultural: Cultural Adaptation and School-Related Attitudes among U.S. Latina/o Youth

    ERIC Educational Resources Information Center

    Acevedo-Polakovich, Ignacio D.; Quirk, Kelley M.; Cousineau, Jennifer R.; Saxena, Suchita R.; Gerhart, James I.

    2014-01-01

    This study examines whether incorporating a multidimensional perspective to the study of the relation between cultural adaptation and academic attitudes among Latinas/os in the United States can clarify this relation. Hypotheses about the relation between cultural adaptation and academic attitudes were examined using data provided by U.S. Latina/o…

  13. Acting Bicultural versus Feeling Bicultural: Cultural Adaptation and School-Related Attitudes among U.S. Latina/o Youth

    ERIC Educational Resources Information Center

    Acevedo-Polakovich, Ignacio D.; Quirk, Kelley M.; Cousineau, Jennifer R.; Saxena, Suchita R.; Gerhart, James I.

    2014-01-01

    This study examines whether incorporating a multidimensional perspective to the study of the relation between cultural adaptation and academic attitudes among Latinas/os in the United States can clarify this relation. Hypotheses about the relation between cultural adaptation and academic attitudes were examined using data provided by U.S. Latina/o…

  14. Adaptive sliding mode control for six-DOF relative motion of spacecraft with input constraint

    NASA Astrophysics Data System (ADS)

    Wu, Jinjie; Liu, Kun; Han, Dapeng

    2013-06-01

    This paper addresses the synchronized control problem of relative position and attitude for spacecraft with input constraint. First, using dual quaternion, the kinematic and dynamic models of the six-degree-of-freedom relative motion of spacecraft are introduced. Second, a new adaptive sliding mode control scheme is proposed to guarantee the globally asymptotic convergence of relative motion despite the presence of control input constraint, parametric uncertainties and external disturbances. A detailed stability analysis of the resulting closed-loop system is included. Finally, simulation results are presented to illustrate the validity and effectiveness of the proposed controller, which has the following properties: (1) explicit accounting for the problem of input constraint, (2) fast convergent rate and accurate results can be obtained, (3) no chattering phenomenon is present in the control torque and control force, (4) self-adaptive regulation law is dynamically adjusted to ensure the tracking errors tend to zero asymptotically, (5) the upper bounds of unknown variables are estimated dynamically.

  15. Selection of aminoacyl-tRNAs at sense codons: the size of the tRNA variable loop determines whether the immediate 3' nucleotide to the codon has a context effect.

    PubMed Central

    Curran, J F; Poole, E S; Tate, W P; Gross, B L

    1995-01-01

    Codon context can affect translational efficiency by several molecular mechanisms. The base stacking interactions between a codon-anticodon complex and the neighboring nucleotide immediately 3' can facilitate translation by amber suppressors and the tRNA structure is also known to modulate the sensitivity to context. In this study the relative rates of aminoacyl-tRNA selection were measured at four sense codons (UGG, CUC, UUC and UCA), in all four 3' nucleotide contexts, through direct competition with a programmed frameshift at a site derived from the release factor 2 gene. Two codons (UGG and UUC) are read by tRNAs with small variable regions and their rates of aminoacyl-tRNA selection correlated with the potential base stacking strength of the 3' neighboring nucleotide. The other two codons (CUC and UCA) are read by tRNAs with large variable regions and the rate of selection of the aminoacyl-tRNAs in these cases varied little among the four contexts. Re-examination of published data on amber suppression also revealed an inverse correlation between context sensitivity and the size of the variable region. Collectively the data suggest that a large variable loop in a tRNA decreases the influence of the 3' context on tRNA selection, probably by strengthening tRNA-ribosomal interactions. PMID:7479072

  16. Random Codon Re-encoding Induces Stable Reduction of Replicative Fitness of Chikungunya Virus in Primate and Mosquito Cells

    PubMed Central

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

    2013-01-01

    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

  17. Dissecting the contributions of GC content and codon usage to gene expression in the model alga Chlamydomonas reinhardtii

    PubMed Central

    Barahimipour, Rouhollah; Strenkert, Daniela; Neupert, Juliane; Schroda, Michael; Merchant, Sabeeha S.; Bock, Ralph

    2015-01-01

    Summary The efficiency of gene expression in all organisms depends on the nucleotide composition of the coding region. GC content and codon usage are the two key sequence features known to influence gene expression, but the underlying molecular mechanisms are not entirely clear. Here we have determined the relative contributions of GC content and codon usage to the efficiency of nuclear gene expression in the unicellular green alga Chlamydomonas reinhardtii. By comparing gene variants that encode an identical amino acid sequence but differ in their GC content and/or codon usage, we show that codon usage is the key factor determining translational efficiency and, surprisingly, also mRNA stability. By contrast, unfavorable GC content affects gene expression at the level of the chromatin structure by triggering heterochromatinization. We further show that mutant algal strains that permit high-level transgene expression are less susceptible to epigenetic transgene suppression and do not establish a repressive chromatin structure at the transgenic locus. Our data disentangle the relationship between GC content and codon usage, and suggest simple strategies to overcome the transgene expression problem in Chlamydomonas. PMID:26402748

  18. Robust adaptive relative position and attitude control for spacecraft autonomous proximity.

    PubMed

    Sun, Liang; Huo, Wei; Jiao, Zongxia

    2016-07-01

    This paper provides new results of the dynamical modeling and controller designing for autonomous close proximity phase during rendezvous and docking in the presence of kinematic couplings and model uncertainties. A globally defined relative motion mechanical model for close proximity operations is introduced firstly. Then, in spite of the kinematic couplings and thrust misalignment between relative rotation and relative translation, robust adaptive relative position and relative attitude controllers are designed successively. Finally, stability of the overall system is proved that the relative position and relative attitude are uniformly ultimately bounded, and the size of the ultimate bound can be regulated small enough by control system parameters. Performance of the controlled overall system is demonstrated via a representative numerical example. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  19. Relating farmer's perceptions of climate change risk to adaptation behaviour in Hungary.

    PubMed

    Li, Sen; Juhász-Horváth, Linda; Harrison, Paula A; Pintér, László; Rounsevell, Mark D A

    2016-10-28

    Understanding how farmers perceive climate change risks and how this affects their willingness to adopt adaptation practices is critical for developing effective climate change response strategies for the agricultural sector. This study examines (i) the perceptual relationships between farmers' awareness of climate change phenomena, beliefs in climate change risks and actual adaptation behaviour, and (ii) how these relationships may be modified by farm-level antecedents related to human, social, financial capitals and farm characteristics. An extensive household survey was designed to investigate the current pattern of adaptation strategies and collect data on these perceptual variables and their potential antecedents from private landowners in Veszprém and Tolna counties, Hungary. Path analysis was used to explore the causal connections between variables. We found that belief in the risk of climate change was heightened by an increased awareness of directly observable climate change phenomena (i.e. water shortages and extreme weather events). The awareness of extreme weather events was a significant driver of adaptation behaviour. Farmers' actual adaptation behaviour was primarily driven by financial motives and managerial considerations (i.e. the aim of improving profit and product sales; gaining farm ownership and the amount of land managed; and, the existence of a successor), and stimulated by an innovative personality and the availability of information from socio-agricultural networks. These results enrich the empirical evidence in support of improving understanding of farmer decision-making processes, which is critical in developing well-targeted adaptation policies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Exercise and comorbidity: the i3-S strategy for developing comorbidity-related adaptations to exercise therapy.

    PubMed

    Dekker, Joost; de Rooij, Mariëtte; van der Leeden, Marike

    2016-01-01

    Exercise therapy is effective in a wide range of chronic diseases. Comorbid disease necessitates adaptations to exercise therapy. Guidance on how to develop such adaptations is currently not available. We present an innovative strategy for the development of comorbidity-related adaptations to exercise therapy in an index disease. We previously developed comorbidity-related adaptations to exercise therapy in osteoarthritis. We now broaden this approach into a general strategy for the development of comorbidity-related adaptations to exercise therapy in an index disease. The i3-S strategy consists of four steps. The first three steps involve creating an inventory of comorbid disease, an inventory of contraindications and restrictions on exercise therapy, and an inventory of potential adaptations to exercise therapy. In the fourth step, this information is synthesized into guidance on comorbidity-related adaptations to exercise therapy in the index disease. The adaptations concern physiological, behavioural and environmental factors. In view of the general effectiveness of exercise therapy and the high prevalence of comorbidity in older people, there is a great need for comorbidity-related adaptations to exercise therapy. We recommend to use and evaluate the i3-S strategy in future research. Exercise therapy is effective in a wide range of chronic diseases. Comorbid disease necessitates adaptations to exercise therapy. Guidance on how to develop such adaptations is currently not available. We present an innovative strategy for the development of comorbidity-related adaptations to exercise therapy in an index disease. Researchers and clinicians can use this strategy to develop guidance on the adaptation of exercise therapy to comorbidity.

  1. [BIG-H3 protein: mutation of codon 124 and corneal amyloidosis].

    PubMed

    Schmitt-Bernard, C-F; Pouliquen, Y; Argilès, A

    2004-05-01

    In 1997, a group of hereditary corneal dystrophies was related to mutations in the TGFBI (BIGH3) gene. Within this group, some corneal dystrophies present particular biochemical features in that they are characterized by corneal amyloid deposition. Contrary to clinical and genetic knowledge, the biochemical characteristics of the encoded protein (Big-h3) and the mechanisms of its amyloid conversion remain unclear. We review the current knowledge on the Big-h3 protein and focus on the behavior of the codon 124 region. We discuss this protein's mechanisms of amyloid conversion from our results and previous reports as well as from other types of amyloidosis. These data provide a better understanding of the putative processes leading to the phenotypic variations linked with their respective codon 124 mutation.

  2. Using brain potentials to understand prism adaptation: the error-related negativity and the P300

    PubMed Central

    MacLean, Stephane J.; Hassall, Cameron D.; Ishigami, Yoko; Krigolson, Olav E.; Eskes, Gail A.

    2015-01-01

    Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN)—a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuomotor responding is shifted to the opposite direction of that initially induced by the prisms. This visuomotor aftereffect has been used to study visuomotor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA's use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN. PMID:26124715

  3. Proteome adaptation to high temperatures in the ectothermic hydrothermal vent Pompeii worm.

    PubMed

    Jollivet, Didier; Mary, Jean; Gagnière, Nicolas; Tanguy, Arnaud; Fontanillas, Eric; Boutet, Isabelle; Hourdez, Stéphane; Segurens, Béatrice; Weissenbach, Jean; Poch, Olivier; Lecompte, Odile

    2012-01-01

    Taking advantage of the massive genome sequencing effort made on thermophilic prokaryotes, thermal adaptation has been extensively studied by analysing amino acid replacements and codon usage in these unicellular organisms. In most cases, adaptation to thermophily is associated with greater residue hydrophobicity and more charged residues. Both of these characteristics are positively correlated with the optimal growth temperature of prokaryotes. In contrast, little information has been collected on the molecular 'adaptive' strategy of thermophilic eukaryotes. The Pompeii worm A. pompejana, whose transcriptome has recently been sequenced, is currently considered as the most thermotolerant eukaryote on Earth, withstanding the greatest thermal and chemical ranges known. We investigated the amino-acid composition bias of ribosomal proteins in the Pompeii worm when compared to other lophotrochozoans and checked for putative adaptive changes during the course of evolution using codon-based Maximum likelihood analyses. We then provided a comparative analysis of codon usage and amino-acid replacements from a greater set of orthologous genes between the Pompeii worm and Paralvinella grasslei, one of its closest relatives living in a much cooler habitat. Analyses reveal that both species display the same high GC-biased codon usage and amino-acid patterns favoring both positively-charged residues and protein hydrophobicity. These patterns may be indicative of an ancestral adaptation to the deep sea and/or thermophily. In addition, the Pompeii worm displays a set of amino-acid change patterns that may explain its greater thermotolerance, with a significant increase in Tyr, Lys and Ala against Val, Met and Gly. Present results indicate that, together with a high content in charged residues, greater proportion of smaller aliphatic residues, and especially alanine, may be a different path for metazoans to face relatively 'high' temperatures and thus a novelty in thermophilic

  4. Heat-Related Mortality and Adaptation to Heat in the United States

    PubMed Central

    Peng, Roger D.; Bell, Michelle L.; Dominici, Francesca

    2014-01-01

    Background: In a changing climate, increasing temperatures are anticipated to have profound health impacts. These impacts could be mitigated if individuals and communities adapt to changing exposures; however, little is known about the extent to which the population may be adapting. Objective: We investigated the hypothesis that if adaptation is occurring, then heat-related mortality would be decreasing over time. Methods: We used a national database of daily weather, air pollution, and age-stratified mortality rates for 105 U.S. cities (covering 106 million people) during the summers of 1987–2005. Time-varying coefficient regression models and Bayesian hierarchical models were used to estimate city-specific, regional, and national temporal trends in heat-related mortality and to identify factors that might explain variation across cities. Results: On average across cities, the number of deaths (per 1,000 deaths) attributable to each 10°F increase in same-day temperature decreased from 51 [95% posterior interval (PI): 42, 61] in 1987 to 19 (95% PI: 12, 27) in 2005. This decline was largest among those ≥ 75 years of age, in northern regions, and in cities with cooler climates. Although central air conditioning (AC) prevalence has increased, we did not find statistically significant evidence of larger temporal declines among cities with larger increases in AC prevalence. Conclusions: The population has become more resilient to heat over time. Yet even with this increased resilience, substantial risks of heat-related mortality remain. Based on 2005 estimates, an increase in average temperatures by 5°F (central climate projection) would lead to an additional 1,907 deaths per summer across all cities. Citation: Bobb JF, Peng RD, Bell ML, Dominici F. 2014. Heat-related mortality and adaptation to heat in the United States. Environ Health Perspect 122:811–816; http://dx.doi.org/10.1289/ehp.1307392 PMID:24780880

  5. No association of the p53 codon 72 polymorphism with malaria in Ghanaian primiparae and Rwandan children.

    PubMed

    Gai, Prabhanjan P; Meese, Stefanie; Bedu-Addo, George; Gahutu, Jean Bosco; Mockenhaupt, Frank P

    2014-06-01

    The p53 protein is a key cell-signaling mediator integrating host responses to various types of stress. A common polymorphism of the encoding TP53 gene (codon 72, Pro > Arg, rs1042522) is associated with susceptibility to virus-related and other cancers. The p53 has also been shown to be central for successful Plasmodium liver stage infection. We examined whether the polymorphism is associated with P. falciparum infection in Ghanaian primiparae and Rwandan children. The allele frequency of TP53 codon 72 Arg was 0.30 among 314 Ghanaian primiparae and 0.31 among 545 Rwandan children, respectively, and it was not associated with infection prevalence or parasite density. This does not exclude p53 to be of pathophysiological relevance in malaria but argues against a major respective role of the TP53 codon 72 polymorphism.

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

    PubMed Central

    Jacob, Etai; Unger, Ron; Horovitz, Amnon

    2015-01-01

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

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

    PubMed

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

    2016-08-19

    Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms. Copyright © 2016, American Association for the Advancement of Science.

  8. A model for codon position bias in RNA editing

    NASA Astrophysics Data System (ADS)

    Bundschuh, Ralf; Liu, Tsunglin

    2006-03-01

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

  9. Model for Codon Position Bias in RNA Editing

    NASA Astrophysics Data System (ADS)

    Liu, Tsunglin; Bundschuh, Ralf

    2005-08-01

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

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

    PubMed

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-07

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

  11. Aeromonas phages encode tRNAs for their overused codons.

    PubMed

    Prabhakaran, Ramanandan; Chithambaram, Shivapriya; Xia, Xuhua

    2014-01-01

    The GC-rich bacterial species, Aeromonas salmonicida, is parasitised by both GC-rich phages (Aeromonas phages - phiAS7 and vB_AsaM-56) and GC-poor phages (Aeromonas phages - 25, 31, 44RR2.8t, 65, Aes508, phiAS4 and phiAS5). Both the GC-rich Aeromonas phage phiAS7 and Aeromonas phage vB_AsaM-56 have nearly identical codon usage bias as their host. While all the remaining seven GC-poor Aeromonas phages differ dramatically in codon usage from their GC-rich host. Here, we investigated whether tRNA encoded in the genome of Aeromonas phages facilitate the translation of phage proteins. We found that tRNAs encoded in the phage genome correspond to synonymous codons overused in the phage genes but not in the host genes.

  12. Why is start codon selection so precise in eukaryotes?

    PubMed Central

    Asano, Katsura

    2014-01-01

    Translation generally initiates with the AUG codon. While initiation at GUG and UUG is permitted in prokaryotes (Archaea and Bacteria), cases of CUG initiation were recently reported in human cells. The varying stringency in translation initiation between eukaryotic and prokaryotic domains largely stems from a fundamental problem for the ribosome in recognizing a codon at the peptidyl-tRNA binding site. Initiation factors specific to each domain of life evolved to confer stringent initiation by the ribosome. The mechanistic basis for high accuracy in eukaryotic initiation is described based on recent findings concerning the role of the multifactor complex (MFC) in this process. Also discussed are whether non-AUG initiation plays any role in translational control and whether start codon accuracy is regulated in eukaryotes. PMID:26779403

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

    NASA Astrophysics Data System (ADS)

    Lind, Christoffer; Sund, Johan; Åqvist, Johan

    2013-12-01

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

  14. Validity of the Adaptation to Age-related Vision Loss Scale in an Australian Cataract Population

    PubMed Central

    Gothwal, Vijaya K.; Wright, Thomas A.; Lamoureux, Ecosse L.; Pesudovs, Konrad

    2010-01-01

    Purpose The Adaptation to Age-related Vision Loss (AVL) scale was developed to measure the adjustment of older adults who are adapting to late-life vision loss. The purpose of this study was to assess whether the AVL scale satisfies the Rasch model in a cataract population. Methods The 24-item AVL scale (18 negatively and 6 positively coded) was mailed to 436 cataract patients for self-administration whilst they were on the waiting list for cataract surgery at the Flinders Eye Centre, Adelaide, South Australia. Rasch analysis was performed to determine whether the items were measuring a single construct (unidimensionality) as examined with fit statistics and principal components analysis (PCA) of the residuals. The ability of the scale to distinguish between the levels of adaptation of the participants (person separation) was investigated, with a value ≥2.0 established as the minimum acceptable. Results The AVL scale was unable to differentiate sufficiently between participants’ levels of adaptation, indicating poor person separation. One item did not fit the construct, causing misfit. Furthermore, the five positively worded items did not appear either to measure the same construct as other items, resulting in lack of unidimensionality evidenced by PCA. Following the deletion of these items, the AVL scale was one-dimensional but a single item continued to misfit, so it had to be deleted, resulting in an 18-item AVL scale. Even so, the discriminating abilities of the scale continued to be poor. Conclusions The AVL scale is not an appropriate measure of adaptation to vision loss in a cataract population.

  15. Transcriptomic Analyses Elucidate Adaptive Differences of Closely-Related Strains of P. aeruginosa in Fuel.

    PubMed

    Gunasekera, Thusitha S; Bowen, Loryn L; Zhou, Carol E; Howard-Byerly, Susan C; Foley, William S; Striebich, Richard C; Dugan, Larry C; Ruiz, Oscar N

    2017-03-17

    Pseudomonas aeruginosa can utilize hydrocarbons, but different strains have varying degrees of adaptation despite their highly conserved genome. P. aeruginosa ATCC 33988 is highly adapted to hydrocarbons while strain PAO1, a human pathogen, is less-adapted and degrades jet fuel at a slower rate than does ATCC 33988. We investigated fuel specific transcriptomic differences between these strains in order to ascertain the underling mechanisms utilized by the adapted strain to proliferate in fuel. During growth in fuel, the genes related to alkane degradation, heat-shock response, membrane proteins, efflux pumps and several novel genes were upregulated in ATCC 33988. Overexpression of alk genes in PAO1 provided some improvement in growth, but not as robust as that of ATCC 33988, suggesting the role of other genes in adaptation. Expression of the function unknown gene PA5359 from ATCC 33988 in PAO1 increased the growth in fuel. Bioinformatic analysis revealed that PA5359 is a predicted lipoprotein with a conserved 'Yx(FWY)xxD' motif, which is shared among bacterial adhesins. Overexpression of the putative RND-efflux pump PA3521-PA3523 increased the growth of ATCC 33988 strain suggesting a possible role in fuel tolerance. Interestingly the PAO1 strain cannot utilize nC8 and nC10. Expression of GFP under the control of alkB promoters confirmed that alk gene promoter polymorphism affects the expression of alk genes. Promoter fusion assays further confirmed that regulation of alk genes was different in the two strains. Protein sequence analysis showed low amino acid differences for many of the upregulated genes, further supporting transcriptional control as the main mechanism for enhanced adaptation.IMPORTANCE These results support that specific signal transduction, gene regulation and coordination of multiple biological responses are required to improve survival, growth and metabolism of fuel in adapted strains. This study provides new insight into the mechanistic

  16. Age-related neuromuscular adaptation does not affect the mechanical efficiency of lower limbs during walking.

    PubMed

    Monaco, V; Micera, S

    2012-07-01

    Ageing involves modifications of the locomotor system which is believed to increase energy consumption. This study aimed at verifying whether neuromuscular adaptation due to ageing, in conjunction with age-related modifications of the muscle-tendon actuators, involves greater muscle-tendon workload. Ten young and 7 elderly healthy subjects were assessed using gait analysis while walking at comparable speed. Planar models of muscle-driven locomotion, accounting for 14 muscles grouped into 9 equivalent actuators, were developed. Muscle-tendon forces were estimated by using the inverse-dynamic based static optimization where cost functions were tuned to capture the different muscle co-activation between groups. Following this, tendon and muscle shortening/lengthening was computed, and muscle-tendon work was estimated and compared between groups. Results showed that both groups produced comparable muscle mechanical work, though shared differently among muscles. In particular, young subjects showed a greater workload of ankle plantaflexor muscles and older subjects used greater eccentric energy at the knee extensors during stance phase. Moreover, young people used more elastic energy than older people. These findings suggest that the combination adaptation due to ageing, in conjunction with age-related modifications of the muscle-tendon actuators, do not significantly increase the overall energetic output of locomotion. Moreover, the motor control system appears to be characterised by a degree of adaptation which allows older individuals to achieve biomechanical efficiency comparable to younger subjects. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Regional aspects of climate change impacts and related adaptation options in European agriculture

    NASA Astrophysics Data System (ADS)

    Eitzinger, J.

    2009-09-01

    Through a change in climatic conditions and variability, for example, extreme weather events (heat waves, droughts, etc.) are likely to occur more frequently in different spatial and time scales in future. Since agriculture is one the man' activities more dependant on weather behaviour, the impact on risks of agricultural production is indeed one of the most important issues in climate change assessments. Therefore an early recognition of risks and implementation of adaptation strategies is crucial as anticipatory and precautionary adaptation is more effective and less costly than forced, last minute, emergency adaptation or retrofitting. Results of climate change impact and adaptation studies often show considerable different results, depending on the spatial scale of regionalisation. However, for a decision maker, only a high spatial resolution of related study results are useful as it can represent local conditions and its spatial variablitiy much better. Therefore the ADAGIO project (adagio-eu.org) was designed to focus on regional studies in order to uncover regional specific problems. In this context a bottom-up approach is used beside the top-down approach of using scientifc studies, involving regional experts and farmers in the evaluation of potential regional vulnerabilites and adaptation options. Preliminary results of the regional studies and gathered feedback from experts and farmers show in general that (increasing) drought and heat is the main factor having impact on agricultural vulnerability not only in the mediterranean region, but also in the Central and Eastern European regions. Another important aspect is that the increasing risk of pest and diseases may play a more important role for agricultural vulnerability than assumed before, however, till now this field is only rarely investigated in Europe. An important aspect is also that there are increasing regional differences in the crop production potential in Europe due to climate change and that

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

    PubMed Central

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

    2013-01-01

    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 pPICZαA-kerAwt, pPICZαA-kerAopti1 and pPICZαA-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 α-keratin (keratin azure) and β-keratin (chicken feather meal). These properties make the P. pastoris pPICZαA-kerAopti1 a suitable candidate for industrial production of keratinases. PMID:23472192

  19. Deletion, insertion and stop codon mutations in vif genes of HIV-1 infecting slow progressor patients.

    PubMed

    Rangel, Héctor Rafael; Garzaro, Domingo; Rodríguez, Anny Karely; Ramírez, Alvaro Hernán; Ameli, Gladys; Del Rosario Gutiérrez, Cristina; Pujol, Flor Helene

    2009-08-30

    Variable progression towards AIDS has been described and has been related to viral and host factors. Around 10% of the HIV-1 infected patients are slow progressors (SP), not presenting with AIDS disease signs even after more than 10 years of infection. Viral gene defects have been associated with the disease progression but more studies are still needed. The sequence of vif and nef were analyzed for HIV-1 infecting 14 SP and 46 normal progressors (NP) patients. Co-circulation of a strain carrying vif deleted gene with the wild type strain was detected in an SP patient with more than 10 years of infection. Other mutations (insertion in aa 63 in one strain, two premature stop codons in another one) were found in viruses infecting two other patients. Except for the SP8 strain, which exhibited a premature stop codon in nef, no gross deletions or insertions were observed in nef genes of both NPs and SPs strains analyzed. Different kind of mutation: deletion, insertion and stop codon, were detected in 3/14 samples from SP, with co-circulation of a 195 bp vif deletion virus with a wild type in one of these patients. Although vif defects do not seem to be a frequent feature in SPs, this study illustrates the importance of analysing this gene, in addition to the multiple factors associated with the long-term non progression to AIDS.

  20. Widespread position-specific conservation of synonymous rare codons within coding sequences

    PubMed Central

    Steele, Aaron; Carmichael, Rory; Rodriguez, Anabel; Specht, Alicia T.; Ngo, Kim; Emrich, Scott

    2017-01-01

    Synonymous rare codons are considered to be sub-optimal for gene expression because they are translated more slowly than common codons. Yet surprisingly, many protein coding sequences include large clusters of synonymous rare codons. Rare codons at the 5’ terminus of coding sequences have been shown to increase translational efficiency. Although a general functional role for synonymous rare codons farther within coding sequences has not yet been established, several recent reports have identified rare-to-common synonymous codon substitutions that impair folding of the encoded protein. Here we test the hypothesis that although the usage frequencies of synonymous codons change from organism to organism, codon rarity will be conserved at specific positions in a set of homologous coding sequences, for example to tune translation rate without altering a protein sequence. Such conservation of rarity–rather than specific codon identity–could coordinate co-translational folding of the encoded protein. We demonstrate that many rare codon cluster positions are indeed conserved within homologous coding sequences across diverse eukaryotic, bacterial, and archaeal species, suggesting they result from positive selection and have a functional role. Most conserved rare codon clusters occur within rather than between conserved protein domains, challenging the view that their primary function is to facilitate co-translational folding after synthesis of an autonomous structural unit. Instead, many conserved rare codon clusters separate smaller protein structural motifs within structural domains. These smaller motifs typically fold faster than an entire domain, on a time scale more consistent with translation rate modulation by synonymous codon usage. While proteins with conserved rare codon clusters are structurally and functionally diverse, they are enriched in functions associated with organism growth and development, suggesting an important role for synonymous codon usage in

  1. XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk

    PubMed Central

    2009-01-01

    Background Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair. Methods We conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis. Results We found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk. Conclusion These findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population. PMID:19919686

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

    PubMed Central

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

    2011-01-01

    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

  3. Adaptive nonlinear robust relative pose control of spacecraft autonomous rendezvous and proximity operations.

    PubMed

    Sun, Liang; Huo, Wei; Jiao, Zongxia

    2017-03-01

    This paper studies relative pose control for a rigid spacecraft with parametric uncertainties approaching to an unknown tumbling target in disturbed space environment. State feedback controllers for relative translation and relative rotation are designed in an adaptive nonlinear robust control framework. The element-wise and norm-wise adaptive laws are utilized to compensate the parametric uncertainties of chaser and target spacecraft, respectively. External disturbances acting on two spacecraft are treated as a lumped and bounded perturbation input for system. To achieve the prescribed disturbance attenuation performance index, feedback gains of controllers are designed by solving linear matrix inequality problems so that lumped disturbance attenuation with respect to the controlled output is ensured in the L2-gain sense. Moreover, in the absence of lumped disturbance input, asymptotical convergence of relative pose are proved by using the Lyapunov method. Numerical simulations are performed to show that position tracking and attitude synchronization are accomplished in spite of the presence of couplings and uncertainties. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  4. Co-evolution of mitochondrial tRNA import and codon usage determines translational efficiency in the green alga Chlamydomonas.

    PubMed

    Salinas, Thalia; Duby, Francéline; Larosa, Véronique; Coosemans, Nadine; Bonnefoy, Nathalie; Motte, Patrick; Maréchal-Drouard, Laurence; Remacle, Claire

    2012-09-01

    Mitochondria from diverse phyla, including protozoa, fungi, higher plants, and humans, import tRNAs from the cytosol in order to ensure proper mitochondrial translation. Despite the broad occurrence of this process, our understanding of tRNA import mechanisms is fragmentary, and crucial questions about their regulation remain unanswered. In the unicellular green alga Chlamydomonas, a precise correlation was found between the mitochondrial codon usage and the nature and amount of imported tRNAs. This led to the hypothesis that tRNA import might be a dynamic process able to adapt to the mitochondrial genome content. By manipulating the Chlamydomonas mitochondrial genome, we introduced point mutations in order to modify its codon usage. We find that the codon usage modification results in reduced levels of mitochondrial translation as well as in subsequent decreased levels and activities of respiratory complexes. These effects are linked to the consequential limitations of the pool of tRNAs in mitochondria. This indicates that tRNA mitochondrial import cannot be rapidly regulated in response to a novel genetic context and thus does not appear to be a dynamic process. It rather suggests that the steady-state levels of imported tRNAs in mitochondria result from a co-evolutive adaptation between the tRNA import mechanism and the requirements of the mitochondrial translation machinery.

  5. Age-related change in fast adaptation mechanisms measured with the scotopic full-field ERG

    PubMed Central

    Panorgias, Athanasios; Werner, John S.

    2017-01-01

    Purpose To quantify the response dynamics of fast adaptation mechanisms of the scotopic ERG in younger and older adults using full-field m-sequence flash stimulation. Methods Scotopic ERGs were measured for a series of flashes separated by 65 ms over a range of 260 ms in 16 younger (20–26, 22.2 ± 2.1; range mean ±1 SD) and 16 older (65–85, 71.2 ± 7) observers without retinal pathology. A short-wavelength (λpeak = 442 nm) LED was used for scotopic stimulation, and the flashes ranged from 0.0001 to 0.01 cd s m−2. The complete binary kernel series was derived from the responses to the m-sequence flash stimulation, and the first- and second-order kernel responses were analyzed. The first-order kernel represented the response to a single, isolated flash, while the second-order kernels reflected the adapted flash responses that followed a single flash by one or more base intervals. B-wave amplitudes of the adapted flash responses were measured and plotted as a function of interstimulus interval to describe the recovery of the scotopic ERG. A linear function was fitted to the linear portion of the recovery curve, and the slope of the line was used to estimate the rate of fast adaptation recovery. Results The amplitudes of the isolated flash responses and rates of scotopic fast adaptation recovery were compared between the younger and older participants using a two-way ANOVA. The isolated flash responses and rates of recovery were found to be significantly lower in the older adults. However, there was no difference between the two age groups in response amplitude or recovery rate after correcting for age-related changes in the density of the ocular media. Conclusions These results demonstrated that the rate of scotopic fast adaptation recovery of normal younger and older adults is similar when stimuli are equated for retinal illuminance. PMID:27126339

  6. Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

    PubMed Central

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  7. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome.

    PubMed

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy.

  8. Adaptive divergence for a fitness-related trait among invasive Ambrosia artemisiifolia populations in France.

    PubMed

    Chun, Young Jin; LE Corre, Valérie; Bretagnolle, François

    2011-04-01

    The impact of natural selection on the adaptive divergence of invasive populations can be assessed by testing the null hypothesis that the extent of quantitative genetic differentiation (Q(ST) ) would be similar to that of neutral molecular differentiation (F(ST) ). Using eight microsatellite loci and a common garden approach, we compared Q(ST) and F(ST) among ten populations of an invasive species Ambrosia artemisiifolia (common ragweed) in France. In a common garden study with varying water and nutrient levels, we measured Q(ST) for five traits (height, total biomass, reproductive allocation, above- to belowground biomass ratio, and days to flowering). Although low F(ST) indicated weak genetic structure and strong gene flow among populations, we found significant diversifying selection (Q(ST) > F(ST) ) for reproductive allocation that may be closely related to fitness. It suggests that abiotic conditions may have exerted selection pressure on A. artemisiifolia populations to differentiate adaptively, such that populations at higher altitude or latitude evolved greater reproductive allocation. As previous studies indicate multiple introductions from various source populations of A. artemisiifolia in North America, our results suggest that the admixture of introduced populations may have increased genetic diversity and additive genetic variance, and in turn, promoted the rapid evolution and adaptation of this invasive species. © 2011 Blackwell Publishing Ltd.

  9. Proteome Adaptation to High Temperatures in the Ectothermic Hydrothermal Vent Pompeii Worm

    PubMed Central

    Jollivet, Didier; Mary, Jean; Gagnière, Nicolas; Tanguy, Arnaud; Fontanillas, Eric; Boutet, Isabelle; Hourdez, Stéphane; Segurens, Béatrice; Weissenbach, Jean; Poch, Olivier; Lecompte, Odile

    2012-01-01

    Taking advantage of the massive genome sequencing effort made on thermophilic prokaryotes, thermal adaptation has been extensively studied by analysing amino acid replacements and codon usage in these unicellular organisms. In most cases, adaptation to thermophily is associated with greater residue hydrophobicity and more charged residues. Both of these characteristics are positively correlated with the optimal growth temperature of prokaryotes. In contrast, little information has been collected on the molecular ‘adaptive’ strategy of thermophilic eukaryotes. The Pompeii worm A. pompejana, whose transcriptome has recently been sequenced, is currently considered as the most thermotolerant eukaryote on Earth, withstanding the greatest thermal and chemical ranges known. We investigated the amino-acid composition bias of ribosomal proteins in the Pompeii worm when compared to other lophotrochozoans and checked for putative adaptive changes during the course of evolution using codon-based Maximum likelihood analyses. We then provided a comparative analysis of codon usage and amino-acid replacements from a greater set of orthologous genes between the Pompeii worm and Paralvinella grasslei, one of its closest relatives living in a much cooler habitat. Analyses reveal that both species display the same high GC-biased codon usage and amino-acid patterns favoring both positively-charged residues and protein hydrophobicity. These patterns may be indicative of an ancestral adaptation to the deep sea and/or thermophily. In addition, the Pompeii worm displays a set of amino-acid change patterns that may explain its greater thermotolerance, with a significant increase in Tyr, Lys and Ala against Val, Met and Gly. Present results indicate that, together with a high content in charged residues, greater proportion of smaller aliphatic residues, and especially alanine, may be a different path for metazoans to face relatively ‘high’ temperatures and thus a novelty in

  10. Adaptive control system having hedge unit and related apparatus and methods

    NASA Technical Reports Server (NTRS)

    Johnson, Eric Norman (Inventor); Calise, Anthony J. (Inventor)

    2003-01-01

    The invention includes an adaptive control system used to control a plant. The adaptive control system includes a hedge unit that receives at least one control signal and a plant state signal. The hedge unit generates a hedge signal based on the control signal, the plant state signal, and a hedge model including a first model having one or more characteristics to which the adaptive control system is not to adapt, and a second model not having the characteristic(s) to which the adaptive control system is not to adapt. The hedge signal is used in the adaptive control system to remove the effect of the characteristic from a signal supplied to an adaptation law unit of the adaptive control system so that the adaptive control system does not adapt to the characteristic in controlling the plant.

  11. Adaptive control system having hedge unit and related apparatus and methods

    NASA Technical Reports Server (NTRS)

    Johnson, Eric Norman (Inventor); Calise, Anthony J. (Inventor)

    2007-01-01

    The invention includes an adaptive control system used to control a plant. The adaptive control system includes a hedge unit that receives at least one control signal and a plant state signal. The hedge unit generates a hedge signal based on the control signal, the plant state signal, and a hedge model including a first model having one or more characteristics to which the adaptive control system is not to adapt, and a second model not having the characteristic(s) to which the adaptive control system is not to adapt. The hedge signal is used in the adaptive control system to remove the effect of the characteristic from a signal supplied to an adaptation law unit of the adaptive control system so that the adaptive control system does not adapt to the characteristic in controlling the plant.

  12. ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocio; Poulon, Fanny; Souied, Eric H

    2016-02-01

    To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

  13. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

    PubMed

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-04-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.

  14. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children

    PubMed Central

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-01-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles–mumps–rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3–5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination. PMID:27195118

  15. Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae

    PubMed Central

    Williams, I.; Richardson, J.; Starkey, A.; Stansfield, I.

    2004-01-01

    In-frame stop codons normally signal termination during mRNA translation, but they can be read as ‘sense’ (readthrough) depending on their context, comprising the 6 nt preceding and following the stop codon. To identify novel contexts directing readthrough, under-represented 5′ and 3′ stop codon contexts from Saccharomyces cerevisiae were identified by genome-wide survey in silico. In contrast with the nucleotide bias 3′ of the stop codon, codon bias in the two codon positions 5′ of the termination codon showed no correlation with known effects on stop codon readthrough. However, individually, poor 5′ and 3′ context elements were equally as effective in promoting stop codon readthrough in vivo, readthrough which in both cases responded identically to changes in release factor concentration. A novel method analysing specific nucleotide combinations in the 3′ context region revealed positions +1,2,3,5 and +1,2,3,6 after the stop codon were most predictive of termination efficiency. Downstream of yeast open reading frames (ORFs), further in-frame stop codons were significantly over-represented at the +1, +2 and +3 codon positions after the ORF, acting to limit readthrough. Thus selection against stop codon readthrough is a dominant force acting on 3′, but not on 5′, nucleotides, with detectable selection on nucleotides as far downstream as +6 nucleotides. The approaches described can be employed to define potential readthrough contexts for any genome. PMID:15602002

  16. Trick-or-Treat Candy-Getters and Hornet Scare Devices: Second Graders Make Creative Inventions Related to Animal Adaptations

    ERIC Educational Resources Information Center

    Rule, Audrey C.; Baldwin, Samantha; Schell, Robert

    2009-01-01

    This repeated measures study examined second graders' (n = 21) performance in creating inventions related to animal adaptations for simple products under two conditions that alternated each week for a six-week period. In the analogy condition, students used form and function analogy object boxes to learn about animal adaptations, applying these…

  17. Health-related quality of life and adaptive behaviors of adolescents with sickle cell disease: stress processing moderators.

    PubMed

    Ziadni, Maisa S; Patterson, Chavis A; Pulgarón, Elizabeth R; Robinson, M Renée; Barakat, Lamia P

    2011-12-01

    The objective of this study was to examine resilience among adolescents with sickle cell disease (SCD), focusing on the interaction of health-related quality of life with stress processing to explain adaptive behavior. Forty-four adolescents with SCD completed paper-and-pencil measures of health-related quality of life, appraisals (hope), pain coping strategies (e.g. adherence), and adaptive behavior. Self-reported health-related quality of life was significantly associated with adaptive behavior, as was adherence. Findings for moderation were mixed. Pain coping strategies moderated the association of health-related quality of life with adaptive behavior such that at lower levels of Coping Strategies Questionnaire (CSQ) Adherence, better quality of life was associated with higher adaptive behavior. Similarly, at higher levels of hope, better quality of life was associated with higher adaptive behavior, and poorer quality of life was associated with lower adaptive behavior. Adolescents with SCD showed resilience, particularly in terms of personal adjustment, that may be explained by their appraisals and stress processing strategies. Interventions to support an optimistic or hopeful outlook and improve adherence to recommendations for medical management of sickle cell pain may result in improved resilience/adaptive behavior.

  18. Trick-or-Treat Candy-Getters and Hornet Scare Devices: Second Graders Make Creative Inventions Related to Animal Adaptations

    ERIC Educational Resources Information Center

    Rule, Audrey C.; Baldwin, Samantha; Schell, Robert

    2009-01-01

    This repeated measures study examined second graders' (n = 21) performance in creating inventions related to animal adaptations for simple products under two conditions that alternated each week for a six-week period. In the analogy condition, students used form and function analogy object boxes to learn about animal adaptations, applying these…

  19. Numerical relations and skill level constrain co-adaptive behaviors of agents in sports teams.

    PubMed

    Silva, Pedro; Travassos, Bruno; Vilar, Luís; Aguiar, Paulo; Davids, Keith; Araújo, Duarte; Garganta, Júlio

    2014-01-01

    Similar to other complex systems in nature (e.g., a hunting pack, flocks of birds), sports teams have been modeled as social neurobiological systems in which interpersonal coordination tendencies of agents underpin team swarming behaviors. Swarming is seen as the result of agent co-adaptation to ecological constraints of performance environments by collectively perceiving specific possibilities for action (affordances for self and shared affordances). A major principle of invasion team sports assumed to promote effective performance is to outnumber the opposition (creation of numerical overloads) during different performance phases (attack and defense) in spatial regions adjacent to the ball. Such performance principles are assimilated by system agents through manipulation of numerical relations between teams during training in order to create artificially asymmetrical performance contexts to simulate overloaded and underloaded situations. Here we evaluated effects of different numerical relations differentiated by agent skill level, examining emergent inter-individual, intra- and inter-team coordination. Groups of association football players (national--NLP and regional-level--RLP) participated in small-sided and conditioned games in which numerical relations between system agents were manipulated (5v5, 5v4 and 5v3). Typical grouping tendencies in sports teams (major ranges, stretch indices, distances of team centers to goals and distances between the teams' opposing line-forces in specific team sectors) were recorded by plotting positional coordinates of individual agents through continuous GPS tracking. Results showed that creation of numerical asymmetries during training constrained agents' individual dominant regions, the underloaded teams' compactness and each team's relative position on-field, as well as distances between specific team sectors. We also observed how skill level impacted individual and team coordination tendencies. Data revealed emergence of

  20. Numerical Relations and Skill Level Constrain Co-Adaptive Behaviors of Agents in Sports Teams

    PubMed Central

    Silva, Pedro; Travassos, Bruno; Vilar, Luís; Aguiar, Paulo; Davids, Keith; Araújo, Duarte; Garganta, Júlio

    2014-01-01

    Similar to other complex systems in nature (e.g., a hunting pack, flocks of birds), sports teams have been modeled as social neurobiological systems in which interpersonal coordination tendencies of agents underpin team swarming behaviors. Swarming is seen as the result of agent co-adaptation to ecological constraints of performance environments by collectively perceiving specific possibilities for action (affordances for self and shared affordances). A major principle of invasion team sports assumed to promote effective performance is to outnumber the opposition (creation of numerical overloads) during different performance phases (attack and defense) in spatial regions adjacent to the ball. Such performance principles are assimilated by system agents through manipulation of numerical relations between teams during training in order to create artificially asymmetrical performance contexts to simulate overloaded and underloaded situations. Here we evaluated effects of different numerical relations differentiated by agent skill level, examining emergent inter-individual, intra- and inter-team coordination. Groups of association football players (national – NLP and regional-level – RLP) participated in small-sided and conditioned games in which numerical relations between system agents were manipulated (5v5, 5v4 and 5v3). Typical grouping tendencies in sports teams (major ranges, stretch indices, distances of team centers to goals and distances between the teams' opposing line-forces in specific team sectors) were recorded by plotting positional coordinates of individual agents through continuous GPS tracking. Results showed that creation of numerical asymmetries during training constrained agents' individual dominant regions, the underloaded teams' compactness and each team's relative position on-field, as well as distances between specific team sectors. We also observed how skill level impacted individual and team coordination tendencies. Data revealed

  1. Adaptive control of gait stability in reducing slip-related backward loss of balance.

    PubMed

    Bhatt, T; Wening, J D; Pai, Y-C

    2006-03-01

    The properties of adaptation within the locomotor and balance control systems directed towards improving one's recovery strategy for fall prevention are not well understood. The purpose of this study was to examine adaptive control of gait stability to repeated slip exposure leading to a reduction in backward loss of balance (and hence in protective stepping). Fourteen young subjects experienced a block of slips during walking. Pre- and post-slip onset stability for all slip trials was obtained as the shortest distance at touchdown (slipping limb) and lift-off (contralateral limb), respectively, between the measured center of mass (COM) state, that is, position and velocity relative to base of support (BOS) and the mathematically predicted threshold for backward loss of balance. An improvement in pre- and post-slip onset stability correlated with a decrease in the incidence of balance loss from 100% (first slip) to 0% (fifth slip). While improvements in pre-slip stability were affected by a proactive anterior shift in COM position, the significantly greater post-slip onset improvements resulted from reductions in BOS perturbation intensity. Such reactive changes in BOS perturbation intensity resulted from a reduction in the demand on post-slip onset braking impulse, which was nonetheless influenced by the proactive adjustments in posture and gait pattern (e.g., the COM position, step length, flat foot landing and increased knee flexion) prior to slip onset. These findings were indicative of the maturing process of the adaptive control. This was characterized by a shift from a reliance on feedback control for postural correction to being influenced by feedforward control, which improved pre-slip stability and altered perturbation intensity, leading to skateover or walkover (>0.05 m or <0.05 m displacement, respectively) adaptive strategies. Finally, the stability at contralateral limb lift-off was highly predictive of balance loss occurrence and its subsequent rapid

  2. Implications of movement-related cortical potential for understanding neural adaptations in muscle strength tasks.

    PubMed

    Lattari, Eduardo; Arias-Carrión, Oscar; Monteiro-Junior, Renato Sobral; Mello Portugal, Eduardo Matta; Paes, Flávia; Menéndez-González, Manuel; Silva, Adriana Cardoso; Nardi, Antonio Egidio; Machado, Sergio

    2014-03-06

    This systematic review aims to provide information about the implications of the movement-related cortical potential (MRCP) in acute and chronic responses to the counter resistance training. The structuring of the methods of this study followed the proposals of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses). It was performed an electronically search in Pubmed/Medline and ISI Web of Knowledge data bases, from 1987 to 2013, besides the manual search in the selected references. The following terms were used: Bereitschaftspotential, MRCP, strength and force. The logical operator "AND" was used to combine descriptors and terms used to search publications. At the end, 11 studies attended all the eligibility criteria and the results demonstrated that the behavior of MRCP is altered because of different factors such as: force level, rate of force development, fatigue induced by exercise, and the specific phase of muscular action, leading to an increase in the amplitude in eccentric actions compared to concentric actions, in acute effects. The long-term adaptations demonstrated that the counter resistance training provokes an attenuation in the amplitude in areas related to the movement, which may be caused by neural adaptation occurred in the motor cortex.

  3. Niche partitioning between close relatives suggests trade-offs between adaptation to local environments and competition

    PubMed Central

    Peterson, Megan L; Rice, Kevin J; Sexton, Jason P

    2013-01-01

    Niche partitioning among close relatives may reflect trade-offs underlying species divergence and coexistence (e.g., between stress tolerance and competitive ability). We quantified the effects of habitat and congeneric species interactions on fitness for two closely related herbaceous plant species, Mimulus guttatus and Mimulus laciniatus, in three common habitat types within their sympatric range. Drought stress strongly reduced survival of M. guttatus in fast-drying seeps occupied by M. laciniatus, suggesting that divergent habitat adaptation maintains this niche boundary. However, neither seedling performance nor congeneric competition explained the absence of M. laciniatus from shady streams where M. guttatus thrives. M. laciniatus may be excluded from this habitat by competition with other species in the community or mature M. guttatus. Species performance and competitive ability were similar in sympatric meadows where plant community stature and the growing season length are intermediate between seeps and streams. Stochastic effects (e.g., dispersal among habitats or temporal variation) may contribute to coexistence in this habitat. Habitat adaptation, species interactions, and stochastic mechanisms influence sympatric distributions for these recently diverged species. PMID:23531923

  4. Resistance training induces supraspinal adaptations: evidence from movement-related cortical potentials.

    PubMed

    Falvo, Michael J; Sirevaag, Erik J; Rohrbaugh, John W; Earhart, Gammon M

    2010-07-01

    Early effects of a resistance training program include neural adaptations at multiple levels of the neuraxis, but direct evidence of central changes is lacking. Plasticity exhibited by multiple supraspinal centers following training may alter slow negative electroencephalographic activity, referred to as movement-related cortical potentials (MRCP). The purpose of this study was to determine whether MRCPs are altered in response to resistance training. Eleven healthy participants (24.6 +/- 3.5 years) performed 3 weeks of explosive unilateral leg extensor resistance training. MRCP were assessed during 60 self-paced leg extensions against a constant nominal load before and after training. Resistance training was effective (P < 0.001) in increasing leg extensor peak force (+22%), rate of force production (+32%) as well as muscle activity (iEMG; +47%, P < 0.05). These changes were accompanied by several MRCP effects. Following training, MRCP amplitude was attenuated at several scalp sites overlying motor-related cortical areas (P < 0.05), and the onset of MRCP at the vertex was 28% (561 ms) earlier. In conclusion, the 3-week training protocol in the present study elicited significant strength gains which were accompanied by neural adaptations at the level of the cortex. We interpret our findings of attenuated cortical demand for submaximal voluntary movement as evidence for enhanced neural economy as a result of resistance training.

  5. GNBP domain of Anopheles darlingi: are polymorphic inversions and gene variation related to adaptive evolution?

    PubMed

    Bridi, L C; Rafael, M S

    2016-02-01

    Anopheles darlingi is the main malaria vector in humans in South America. In the Amazon basin, it lives along the banks of rivers and lakes, which responds to the annual hydrological cycle (dry season and rainy season). In these breeding sites, the larvae of this mosquito feed on decomposing organic and microorganisms, which can be pathogenic and trigger the activation of innate immune system pathways, such as proteins Gram-negative binding protein (GNBP). Such environmental changes affect the occurrence of polymorphic inversions especially at the heterozygote frequency, which confer adaptative advantage compared to homozygous inversions. We mapped the GNBP probe to the An. darlingi 2Rd inversion by fluorescent in situ hybridization (FISH), which was a good indicator of the GNBP immune response related to the chromosomal polymorphic inversions and adaptative evolution. To better understand the evolutionary relations and time of divergence of the GNBP of An. darlingi, we compared it with nine other mosquito GNBPs. The results of the phylogenetic analysis of the GNBP sequence between the species of mosquitoes demonstrated three clades. Clade I and II included the GNBPB5 sequence, and clade III the sequence of GNBPB1. Most of these sequences of GNBP analyzed were homologous with that of subfamily B, including that of An. gambiae (87 %), therefore suggesting that GNBP of An. darling belongs to subfamily B. This work helps us understand the role of inversion polymorphism in evolution of An. darlingi.

  6. Implications of movement-related cortical potential for understanding neural adaptations in muscle strength tasks

    PubMed Central

    2014-01-01

    This systematic review aims to provide information about the implications of the movement-related cortical potential (MRCP) in acute and chronic responses to the counter resistance training. The structuring of the methods of this study followed the proposals of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses). It was performed an electronically search in Pubmed/Medline and ISI Web of Knowledge data bases, from 1987 to 2013, besides the manual search in the selected references. The following terms were used: Bereitschaftspotential, MRCP, strength and force. The logical operator “AND” was used to combine descriptors and terms used to search publications. At the end, 11 studies attended all the eligibility criteria and the results demonstrated that the behavior of MRCP is altered because of different factors such as: force level, rate of force development, fatigue induced by exercise, and the specific phase of muscular action, leading to an increase in the amplitude in eccentric actions compared to concentric actions, in acute effects. The long-term adaptations demonstrated that the counter resistance training provokes an attenuation in the amplitude in areas related to the movement, which may be caused by neural adaptation occurred in the motor cortex. PMID:24602228

  7. Sliding of a 43S ribosomal complex from the recognized AUG codon triggered by a delay in eIF2-bound GTP hydrolysis.

    PubMed

    Terenin, Ilya M; Akulich, Kseniya A; Andreev, Dmitry E; Polyanskaya, Sofya A; Shatsky, Ivan N; Dmitriev, Sergey E

    2016-02-29

    During eukaryotic translation initiation, 43S ribosomal complex scans mRNA leader unless an AUG codon in an appropriate context is found. Establishing the stable codon-anticodon base-pairing traps the ribosome on the initiator codon and triggers structural rearrangements, which lead to Pi release from the eIF2-bound GTP. It is generally accepted that AUG recognition by the scanning 43S complex sets the final point in the process of start codon selection, while latter stages do not contribute to this process. Here we use translation reconstitution approach and kinetic toe-printing assay to show that after the 48S complex is formed on an AUG codon, in case GTP hydrolysis is impaired, the ribosomal subunit is capable to resume scanning and slides downstream to the next AUG. In contrast to leaky scanning, this sliding is not limited to AUGs in poor nucleotide contexts and occurs after a relatively long pause at the recognized AUG. Thus, recognition of an AUG per se does not inevitably lead to this codon being selected for initiation of protein synthesis. Instead, it is eIF5-induced GTP hydrolysis and Pi release that irreversibly trap the 48S complex, and this complex is further stabilized by eIF5B and 60S joining. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. [Assessing work-related stress: an Italian adaptation of the HSE Management Standards Work-Related Stress Indicator Tool].

    PubMed

    Marcatto, Francesco; D'Errico, Giuseppe; Di Blas, Lisa; Ferrante, Donatella

    2011-01-01

    The aim of this paper is to present a preliminary validation of an Italian adaptation of the HSE Management Standards Work-Related Stress Indicator Tool (IT), an instrument for assessing work-related stress at the organizational level, originally developed in Britain by the Health and Safety Executive. A scale that assesses the physical work environment has been added to the original version of the IT. 190 employees of the University of Trieste have been enrolled in the study. A confirmatory analysis showed a satisfactory fit of the eight-factors structure of the instrument. Further psychometric analysis showed adequate internal consistency of the IT scales and good criterion validity, as evidenced by the correlations with self-perception of stress, work satisfaction and motivation. In conclusion, the Indicator Tool proved to be a valid and reliable instrument for the assessment of work-related stress at the organizational level, and it is also compatible with the instructions provided by the Ministry of Labour and Social Policy (Circular letter 18/11/2010).

  9. Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration.

    PubMed

    Laíns, Inês; Miller, John B; Park, Dong H; Tsikata, Edem; Davoudi, Samaneh; Rahmani, Safa; Pierce, Jonathan; Silva, Rufino; Chen, Teresa C; Kim, Ivana K; Vavvas, Demetrios; Miller, Joan W; Husain, Deeba

    2017-09-01

    To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). Prospective, cross-sectional study. Patients with AMD and a comparison group (>50 years) without any vitreoretinal disease. All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2° circle, 5° superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. We included 137 eyes (n = 77 subjects), 72.3% (n = 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot (ß = 4.8, P < 0.001), as well as any abnormalities in the macula (ß = 2.4, P = 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n = 76, 55.5%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs (ß = 2.00, P = 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P = 0.001 for both) or anywhere in the macula (P < 0.001 for both). Within the

  10. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-12-1-0377 TITLE: The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in 5a. CONTRACT NUMBER PR110178 Bone...adapt to mechanical loading (exercise). Degeneration in peripheral nerve function with age may be one of these mechanisms, as neuropeptides affect

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

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2009-01-01

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

  13. Atlantic salmon populations reveal adaptive divergence of immune related genes - a duplicated genome under selection.

    PubMed

    Kjærner-Semb, Erik; Ayllon, Fernando; Furmanek, Tomasz; Wennevik, Vidar; Dahle, Geir; Niemelä, Eero; Ozerov, Mikhail; Vähä, Juha-Pekka; Glover, Kevin A; Rubin, Carl J; Wargelius, Anna; Edvardsen, Rolf B

    2016-08-11

    Populations of Atlantic salmon display highly significant genetic differences with unresolved molecular basis. These differences may result from separate postglacial colonization patterns, diversifying natural selection and adaptation, or a combination. Adaptation could be influenced or even facilitated by the recent whole genome duplication in the salmonid lineage which resulted in a partly tetraploid species with duplicated genes and regions. In order to elucidate the genes and genomic regions underlying the genetic differences, we conducted a genome wide association study using whole genome resequencing data from eight populations from Northern and Southern Norway. From a total of ~4.5 million sequencing-derived SNPs, more than 10 % showed significant differentiation between populations from these two regions and ten selective sweeps on chromosomes 5, 10, 11, 13-15, 21, 24 and 25 were identified. These comprised 59 genes, of which 15 had one or more differentiated missense mutation. Our analysis showed that most sweeps have paralogous regions in the partially tetraploid genome, each lacking the high number of significant SNPs found in the sweeps. The most significant sweep was found on Chr 25 and carried several missense mutations in the antiviral mx genes, suggesting that these populations have experienced differing viral pressures. Interestingly the second most significant sweep, found on Chr 5, contains two genes involved in the NF-KB pathway (nkap and nkrf), which is also a known pathogen target that controls a large number of processes in animals. Our results show that natural selection acting on immune related genes has contributed to genetic divergence between salmon populations in Norway. The differences between populations may have been facilitated by the plasticity of the salmon genome. The observed signatures of selection in duplicated genomic regions suggest that the recently duplicated genome has provided raw material for evolutionary adaptation.

  14. Relative Crystallinity of Plant Biomass: Studies on Assembly, Adaptation and Acclimation

    PubMed Central

    Harris, Darby; DeBolt, Seth

    2008-01-01

    Plant biomechanical design is central to cell shape, morphogenesis, reproductive performance and protection against environmental and mechanical stress. The cell wall forms the central load bearing support structure for plant design, yet a mechanistic understanding of its synthesis is incomplete. A key tool for studying the structure of cellulose polymorphs has been x-ray diffraction and fourier transform infrared spectroscopy (FTIR). Relative crystallinity index (RCI) is based on the x-ray diffraction characteristics of two signature peaks and we used this technique to probe plant assembly, adaptation and acclimation. Confocal microscopy was used to visualize the dynamics of cellulose synthase in transgenic Arabidopsis plants expressing a homozygous YFP::CESA6. Assembly: RCI values for stems and roots were indistinguishable but leaves had 23.4 and 21.6% lower RCI than stems and roots respectively. Adaptation: over 3-fold variability in RCI was apparent in leaves from 35 plant species spanning Ordovician to Cretaceous periods. Within this study, RCI correlated positively with leaf geometric constraints and with mass per unit area, suggestive of allometry. Acclimation: biomass crystallinity was found to decrease under conditions of thigmomorphogenesis in Arabidopsis. Further, in etiolated pea hypocotyls, RCI values also decreased compared to plants that were grown in light, consistent with alterations in FTIR cellulose fingerprint peaks and live cell imaging experiments revealing rapid orientation of the YFP::cellulose synthase-6 array in response to light. Herein, results and technical challenges associated with the structure of the cell wall that gives rise to sample crystallinity are presented and examined with respect to adaptation, acclimation and assembly in ecosystem-level processes. PMID:18682826

  15. Adaptive coping strategies of affected family members of a relative with substance misuse: A qualitative study.

    PubMed

    McCann, Terence V; Lubman, Dan I

    2017-08-03

    To explore the coping strategies used by affected family members of a relative with substance misuse. Families play an important role in supporting a relative with substance misuse. However, the experience often has an adverse effect on their general well-being, the extent of which depends largely on their coping strategies. An interpretative phenomenological analysis study. Data were collected between January - December 2015. Semistructured, audio-recorded qualitative interviews were conducted with 31 affected family members. Three main themes and related subthemes were abstracted from the data illustrating how participants coped with their relative's substance misuse: (1) Seeking timely access to evidence-based information; (2) Enhancing personal coping strategies and (3) Accessing informal and formal support. Greater investment is needed in support services for affected family members, particularly in regional and rural areas. A wide range of accessible evidence-based information and informal and formal support, including telephone and online support, is needed to assist them to cope in this crucial support-giving role. Affected family members need to adopt a flexible set of coping strategies while supporting a relative with substance misuse. Family and friends, alcohol and other drug services, mental health nurses and other clinicians have a critical role providing emotional, instrumental and educational support to affected family members to enhance their adaptive coping strategies. © 2017 John Wiley & Sons Ltd.

  16. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  17. High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene.

    PubMed

    Sills, R C; Hong, H L; Melnick, R L; Boorman, G A; Devereux, T R

    1999-04-01

    Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras proto-oncogenes in chloroprene-induced lung and HG neoplasms. K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82). Both K- and H-ras codon 61 A-->T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A-->T transversion at K-ras codon 61. This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A-->T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A-->T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A-->T transversion at K-ras codon 61. This differed from 1,3-butadiene, where K-ras codon 13 G-->C transitions and H-ras codon 61 A-->G transitions were the predominant mutations. The major finding of K-ras A-->T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens.

  18. Neuroelectric adaptations to cognitive processing in virtual environments: an exercise-related approach.

    PubMed

    Vogt, Tobias; Herpers, Rainer; Scherfgen, David; Strüder, Heiko K; Schneider, Stefan

    2015-04-01

    Recently, virtual environments (VEs) are suggested to encourage users to exercise regularly. The benefits of chronic exercise on cognitive performance are well documented in non-VE neurophysiological and behavioural studies. Based on event-related potentials (ERP) such as the N200 and P300, cognitive processing may be interpreted on a neuronal level. However, exercise-related neuroelectric adaptation in VE remains widely unclear and thus characterizes the primary aim of the present study. Twenty-two healthy participants performed active (moderate cycling exercise) and passive (no exercise) sessions in three VEs (control, front, surround), each generating a different sense of presence. Within sessions, conditions were randomly assigned, each lasting 5 min and including a choice reaction-time task to assess cognitive performance. According to the international 10:20 system, EEG with real-time triggered stimulus onset was recorded, and peaks of N200 and P300 components (amplitude, latency) were exported for analysis. Heart rate was recorded, and sense of presence assessed prior to and following each session and condition. Results revealed an increase in ERP amplitudes (N200: p < 0.001; P300: p < 0.001) and latencies (N200: p < 0.001) that were most pronounced over fronto-central and occipital electrode sites relative to an increased sense of presence (p < 0.001); however, ERP were not modulated by exercise (each p > 0.05). Hypothesized to mirror cognitive processing, decreases of cognitive performance's accuracy and reaction time failed significance. With respect to previous research, the present neuroelectric adaptation gives reason to believe in compensative neuronal resources that balance demanding cognitive processing in VE to avoid behavioural inefficiency.

  19. Reduced Protein Expression in a Virus Attenuated by Codon Deoptimization

    PubMed Central

    Jack, Benjamin R.; Boutz, Daniel R.; Paff, Matthew L.; Smith, Bartram L.; Bull, James J.; Wilke, Claus O.

    2017-01-01

    A general means of viral attenuation involves the extensive recoding of synonymous codons in the viral genome. The mechanistic underpinnings of this approach remain unclear, however. Using quantitative proteomics and RNA sequencing, we explore the molecular basis of attenuation in a strain of bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal codons. We do not detect transcriptional effects from recoding. Proteomic observations reveal that translation is halved for the recoded major capsid gene, and a more modest reduction applies to several coexpressed downstream genes. We observe no changes in protein abundances of other coexpressed genes that are encoded upstream. Viral burst size, like capsid protein abundance, is also decreased by half. Together, these observations suggest that, in this virus, reduced translation of an essential polycistronic transcript and diminished virion assembly form the molecular basis of attenuation. PMID:28698233

  20. Vulnerability and adaptation to climate-related fire impacts in rural and urban interior Alaska

    USGS Publications Warehouse

    Trainor, Sarah F.; Calef, Monika; Natcher, David; Chapin, F. Stuart; McGuire, Anthony; Huntington, Orville; Duffy, Paul A; Rupp, T. Scott; DeWilde, La'Ona; Kwart, Mary; Fresco, Nancy; Lovecraft, Amy Lauren

    2009-01-01

    This paper explores whether fundamental differences exist between urban and rural vulnerability to climate-induced changes in the fire regime of interior Alaska. We further examine how communities and fire managers have responded to these changes and what additional adaptations could be put in place. We engage a variety of social science methods, including demographic analysis, semi-structured interviews, surveys, workshops and observations of public meetings. This work is part of an interdisciplinary study of feedback and interactions between climate, vegetation, fire and human components of the Boreal forest social–ecological system of interior Alaska. We have learned that although urban and rural communities in interior Alaska face similar increased exposure to wildfire as a result of climate change, important differences exist in their sensitivity to these biophysical, climate-induced changes. In particular, reliance on wild foods, delayed suppression response, financial resources and institutional connections vary between urban and rural communities. These differences depend largely on social, economic and institutional factors, and are not necessarily related to biophysical climate impacts per se. Fire management and suppression action motivated by political, economic or other pressures can serve as unintentional or indirect adaptation to climate change. However, this indirect response alone may not sufficiently reduce vulnerability to a changing fire regime. More deliberate and strategic responses may be required, given the magnitude of the expected climate change and the likelihood of an intensification of the fire regime in interior Alaska.

  1. Relating adaptive genetic traits to climate for Sandberg bluegrass from the intermountain western United States.

    PubMed

    Johnson, Richard C; Horning, Matthew E; Espeland, Erin K; Vance-Borland, Ken

    2015-02-01

    Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source population climate. Common gardens were established at two intermountain west sites with progeny from two maternal parents from each of 130 wild populations. Data were collected over 2 years at each site on fifteen plant traits associated with production, phenology, and morphology. Analyses of variance revealed strong population differences for all plant traits (P < 0.0001), indicating genetic variation. Both the canonical correlation and linear correlation established associations between source populations and climate variability. Populations from warmer, more arid climates had generally lower dry weight, earlier phenology, and smaller, narrower leaves than those from cooler, moister climates. The first three canonical variates were regressed with climate variables resulting in significant models (P < 0.0001) used to map 12 seed zones. Of the 700 981 km(2) mapped, four seed zones represented 92% of the area in typically semi-arid and arid regions. The association of genetic variation with source climates in the intermountain west suggested climate driven natural selection and evolution. We recommend seed transfer zones and population movement guidelines to enhance adaptation and diversity for large-scale restoration projects.

  2. Relationship between age-related gait adaptations and required coefficient of friction

    PubMed Central

    Kim, Sukwon; Lockhart, Thurmon; Yoon, Hoon-Yong

    2010-01-01

    A laboratory study was conducted to evaluate if age-related gait adaptations in walking velocity, step length and heel contact velocity could adversely influence friction demand characteristics (i.e. RCOF) and the likelihood of slip initiation. Additionally, relationship between transitional acceleration of the whole body center-of-mass (COM) and friction demand was assessed between young and older participants. Fourteen younger (7 females and 7 males, 18–30 years old) and 14 older (7 females and 7 males, over 65 years old) adults participated in the study. While wearing a safety harness, all participants walked at their preferred gait speed for approximately 20 min on the linear walking track, and synchronized ground reaction forces and posture data were captured using the force plates and six infrared cameras, respectively. The results indicated that older adults walked slower with slower heel contact velocity, and produced lower friction demand (i.e. RCOF) in comparison to younger adults. However, ANCOVA indicated that the differences in heel contact velocity between the two age groups were due to effects of walking velocity. The multiple regression and bivariate regression analyses suggested that, for older adults, heel contact velocity was a predictor for the RCOF, whereas, for younger adults, walking velocity, step length and transitional acceleration of the whole body COM were the factors contributing to the RCOF. In conclusion, the present study suggested that gait adaptations among the elderly must be considered when predicting the likelihood of slip initiation. PMID:20582254

  3. Relating adaptive genetic traits to climate for Sandberg bluegrass from the intermountain western United States

    PubMed Central

    Johnson, Richard C; Horning, Matthew E; Espeland, Erin K; Vance-Borland, Ken

    2015-01-01

    Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source population climate. Common gardens were established at two intermountain west sites with progeny from two maternal parents from each of 130 wild populations. Data were collected over 2 years at each site on fifteen plant traits associated with production, phenology, and morphology. Analyses of variance revealed strong population differences for all plant traits (P < 0.0001), indicating genetic variation. Both the canonical correlation and linear correlation established associations between source populations and climate variability. Populations from warmer, more arid climates had generally lower dry weight, earlier phenology, and smaller, narrower leaves than those from cooler, moister climates. The first three canonical variates were regressed with climate variables resulting in significant models (P < 0.0001) used to map 12 seed zones. Of the 700 981 km2 mapped, four seed zones represented 92% of the area in typically semi-arid and arid regions. The association of genetic variation with source climates in the intermountain west suggested climate driven natural selection and evolution. We recommend seed transfer zones and population movement guidelines to enhance adaptation and diversity for large-scale restoration projects. PMID:25685192

  4. Adaptive evolution of foraging-related traits in a predator-prey community.

    PubMed

    Zu, Jian; Mimura, Masayasu; Takeuchi, Yasuhiro

    2011-01-07

    In this paper, with the method of adaptive dynamics and geometric technique, we investigate the adaptive evolution of foraging-related phenotypic traits in a predator-prey community with trade-off structure. Specialization on one prey type is assumed to go at the expense of specialization on another. First, we identify the ecological and evolutionary conditions that allow for evolutionary branching in predator phenotype. Generally, if there is a small switching cost near the singular strategy, then this singular strategy is an evolutionary branching point, in which predator population will change from monomorphism to dimorphism. Second, we find that if the trade-off curve is globally convex, predator population eventually branches into two extreme specialists, each completely specializing on a particular prey species. However, if the trade-off curve is concave-convex-concave, after branching in predator phenotype, the two predator species will evolve to an evolutionarily stable dimorphism at which they can continue to coexist. The analysis reveals that an attractive dimorphism will always be evolutionarily stable and that no further branching is possible under this model.

  5. Mapping Heat-related Risks for Community-based Adaptation Planning under Uncertainty

    NASA Astrophysics Data System (ADS)

    Bai, Yingjiu; Kaneko, Ikuyo; Kobayashi, Hikaru; Kurihara, Kazuo; Sasaki, Hidetaka; Murata, Akihiko; Takayabu, Izuru

    2016-04-01

    Climate change is leading to more frequent and intense heat waves. Recently, epidemiologic findings on heat-related health impacts have reinforced our understanding of the mortality impacts of extreme heat. This research has several aims: 1) to promote climate prediction services with spatial and temporal information on heat-related risks, using GIS (Geographical Information System), and digital mapping techniques; 2) to propose a visualization approach to articulating the evolution of local heat-health responses over time and the evaluation of new interventions for the implementation of valid community-based adaptation strategies and reliable actionable planning; and 3) to provide an appropriate and simple method of adjusting bias and quantifying the uncertainty in future outcomes, so that regional climate projections may be transcribed into useful forms for a wide variety of different users. Following the 2003 European heat wave, climatologists, medical specialists, and social scientists expedited efforts to revise and integrate risk governance frameworks for communities to take appropriate and effective actions themselves. Recently, the Coupled Model Intercomparison Project (CMIP) methodology has made projections possible for anyone wanting to openly access state-of-the-art climate model outputs and climate data to provide the backbone for decisions. Furthermore, the latest high-solution regional climate model (RCM) has been a huge increase in the volumes of data available. In this study, we used high-quality hourly projections (5-km resolution) from the Non-Hydrostatic Regional Climate Model (NHRCM-5km), following the SRES-A1B scenario developed by the Meteorological Research Institute (MRI) and observational data from the Automated Meteorological Data Acquisition System, Japan Meteorological Agency (JMA). The NHRCM-5km is a dynamic downscaling of results from the MRI-AGCM3.2S (20-km resolution), an atmospheric general circulation model (AGCM) driven by the

  6. Changes in Ecosystem Services and related Livelihoods in the Mekong Delta: vulnerabilities and adaptation strategies

    NASA Astrophysics Data System (ADS)

    Sebesvari, Z.; Renaud, F. G.

    2014-12-01

    The Mekong Delta (Vietnam) is highly vulnerable to the many impacts of global environmental change as well as to the accelerating anthropogenic changes in the catchment and in the delta itself. Today the delta is an agricultural landscape controlled by engineering structures such as channels, dykes, embankments, and sluice gates. These structures have been constructed gradually over the last 200 years mainly for irrigation and flood control in the upper part of the delta and to control saline intrusion in the coastal areas. Recent changes in the hydrology mainly driven by upstream hydropower development on the mainstream and the tributaries of the Mekong will likely have far reaching impacts on the delta´s social-ecological systems through changes in e.g. sedimentation processes, nutrient transport as well as the health of aquatic ecosystems. Further threats to the delta include sea level rise and an increase in seasonal rainfall variability leading to an increase in flood variability. These changes affect the lives of millions of low-income inhabitants who depend on the ecosystem services provided by the Mekong for their livelihoods and sustenance. Since the changes in ecosystem service provision are occurring relatively fast while the resource dependency of the delta population is very high, adaptation becomes a challenge. An assessment of livelihood dependencies on ecosystem services requires an understanding of ecosystem services affected by different drivers of change, as well as of the types of livelihoods likely to be jeopardized as a result of these changes. We will present main ecosystem services supporting specific livelihoods, discuss how they are threatened, and analyse the merits of potential solutions. Options based solely on grey infrastructure might be problematic on the long term while an integration of ecosystem based solution such as a (re)adaptation of agricultural production systems to floods in the upper delta might be a more sustainable

  7. Effect of replication on the third base of codons

    NASA Astrophysics Data System (ADS)

    Cebrat, S.; Dudek, M. R.; Gierlik, A.; Kowalczuk, M.; Mackiewicz, P.

    We have analyzed third position in codons and have observed strong long-range correlations along DNA sequence. We have shown that the correlations are caused mostly by asymmetric replication. In the analysis, we have used a DNA walk (spider analysis Cebrat et al., Microbial Comparative Genomics 2(4) (1997) 259-268) in two-dimensional space [A-T,G-C]. The particular case of the E.coli sequence has been studied in detail.

  8. Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

    PubMed Central

    Qiao, Qin; Wang, Qia; Han, Xi; Guan, Yanlong; Sun, Hang; Zhong, Yang; Huang, Jinling; Zhang, Ticao

    2016-01-01

    The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants. PMID:26906946

  9. Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

    NASA Astrophysics Data System (ADS)

    Qiao, Qin; Wang, Qia; Han, Xi; Guan, Yanlong; Sun, Hang; Zhong, Yang; Huang, Jinling; Zhang, Ticao

    2016-02-01

    The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants.

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

    PubMed

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

    2014-11-04

    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.

  11. Testing the Adaptation to Poverty-Related Stress Model: Predicting Psychopathology Symptoms in Families Facing Economic Hardship

    ERIC Educational Resources Information Center

    Wadsworth, Martha E.; Raviv, Tali; Santiago, Catherine DeCarlo; Etter, Erica M.

    2011-01-01

    This study tested the Adaptation to Poverty-related Stress Model and its proposed relations between poverty-related stress, effortful and involuntary stress responses, and symptoms of psychopathology in an ethnically diverse sample of low-income children and their parents. Prospective Hierarchical Linear Modeling analyses conducted with 98…

  12. Testing the Adaptation to Poverty-Related Stress Model: Predicting Psychopathology Symptoms in Families Facing Economic Hardship

    ERIC Educational Resources Information Center

    Wadsworth, Martha E.; Raviv, Tali; Santiago, Catherine DeCarlo; Etter, Erica M.

    2011-01-01

    This study tested the Adaptation to Poverty-related Stress Model and its proposed relations between poverty-related stress, effortful and involuntary stress responses, and symptoms of psychopathology in an ethnically diverse sample of low-income children and their parents. Prospective Hierarchical Linear Modeling analyses conducted with 98…

  13. Synonymous codon usage pattern in mitochondrial CYB gene in pisces, aves, and mammals.

    PubMed

    Uddin, Arif; Chakraborty, Supriyo

    2017-03-01

    Cytochrome b (CYB) protein plays an important role in complex III of the mitochondrial oxidative phosphorylation. Codon usage is the phenomenon of non-uniform usage of synonymous codons. In the present study, we report the pattern of codon usage in MT-CYB gene using various codon usage parameters. Nucleotide composition such as % of C and T was higher than A and G in pisces. In aves, % of A and C was higher than T and G but in mammals, A and T was higher than C and G. Heat map shows that AT-ending codons were mostly negative and GC-ending codons were mostly positive. From the heat map based on RSCU values, it is evident that codon usage prefers A/C at the third codon position and it was less towards T/G in its third codon position. The codons absent in pisces were AGT (except Toxotes chatareus), TGT, and CAG (except Elasma zonatum). The codons such as AGT (except Falco peregrinus), CGT (except Vidua chalybeata), and ACG (except Aythya americana) were absent in aves whereas, in mammals, the absent codons were namely CAG (except Canis familiaris) and ACG (except Rattus norvegicus). Codon usage bias was low in pisces, aves, and mammals. The frequency of leucine was the highest in the amino acid and cysteine was the lowest. Correlation analysis further suggests that mutation pressure is mainly responsible for codon usage pattern. Natural selection might also play a vital role in codon usage pattern but it was weaker than mutation pressure.

  14. Inducible suppression of global translation by overuse of rare codons.

    PubMed

    Kobayashi, Hideki

    2015-04-01

    Recently, artificial gene networks have been developed in synthetic biology to control gene expression and make organisms as controllable as robots. Here, I present an artificial posttranslational gene-silencing system based on the codon usage bias and low tRNA content corresponding to minor codons. I engineered the green fluorescent protein (GFP) gene to inhibit translation indirectly with the lowest-usage codons to monopolize various minor tRNAs (lgfp). The expression of lgfp interfered nonspecifically with the growth of Escherichia coli, Saccharomyces cerevisiae, human HeLa cervical cancer cells, MCF7 breast cancer cells, and HEK293 kidney cells, as well as phage and adenovirus expansion. Furthermore, insertion of lgfp downstream of a phage response promoter conferred phage resistance on E. coli. Such engineered gene silencers could act as components of biological networks capable of functioning with suitable promoters in E. coli, S. cerevisiae, and human cells to control gene expression. The results presented here show general suppressor artificial genes for live cells and viruses. This robust system provides a gene expression or cell growth control device for artificially synthesized gene networks.

  15. Codon Distribution in Error-Detecting Circular Codes

    PubMed Central

    Fimmel, Elena; Strüngmann, Lutz

    2016-01-01

    In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick’s hypothesis proved to be wrong, in 1996, Arquès and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self-complementary C3 and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising) result, it is shown that the codons can be separated into very few classes (three, or five, or six) with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C3 codes to maximal self-complementary circular codes. PMID:26999215

  16. A Synthetic Approach to Stop-Codon Scanning Mutagenesis

    PubMed Central

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

    2011-01-01

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

  17. Codon Distribution in Error-Detecting Circular Codes.

    PubMed

    Fimmel, Elena; Strüngmann, Lutz

    2016-03-15

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

  18. Translational Redefinition of UGA Codons Is Regulated by Selenium Availability*

    PubMed Central

    Howard, Michael T.; Carlson, Bradley A.; Anderson, Christine B.; Hatfield, Dolph L.

    2013-01-01

    Incorporation of selenium into ∼25 mammalian selenoproteins occurs by translational recoding whereby in-frame UGA codons are redefined to encode the selenium containing amino acid, selenocysteine (Sec). Here we applied ribosome profiling to examine the effect of dietary selenium levels on the translational mechanisms controlling selenoprotein synthesis in mouse liver. Dietary selenium levels were shown to control gene-specific selenoprotein expression primarily at the translation level by differential regulation of UGA redefinition and Sec incorporation efficiency, although effects on translation initiation and mRNA abundance were also observed. Direct evidence is presented that increasing dietary selenium causes a vast increase in ribosome density downstream of UGA-Sec codons for a subset of selenoprotein mRNAs and that the selenium-dependent effects on Sec incorporation efficiency are mediated in part by the degree of Sec-tRNA[Ser]Sec Um34 methylation. Furthermore, we find evidence for translation in the 5′-UTRs for a subset of selenoproteins and for ribosome pausing near the UGA-Sec codon in those mRNAs encoding the selenoproteins most affected by selenium availability. These data illustrate how dietary levels of the trace element selenium can alter the readout of the genetic code to affect the expression of an entire class of proteins. PMID:23696641

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

    PubMed Central

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

    2016-01-01

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

  20. Avoided Heat-Related Mortality through Climate Adaptation Strategies in Three US Cities

    PubMed Central

    Stone, Brian; Vargo, Jason; Liu, Peng; Habeeb, Dana; DeLucia, Anthony; Trail, Marcus; Hu, Yongtao; Russell, Armistead

    2014-01-01

    Heat-related mortality in US cities is expected to more than double by the mid-to-late 21st century. Rising heat exposure in cities is projected to result from: 1) climate forcings from changing global atmospheric composition; and 2) local land surface characteristics responsible for the urban heat island effect. The extent to which heat management strategies designed to lessen the urban heat island effect could offset future heat-related mortality remains unexplored in the literature. Using coupled global and regional climate models with a human health effects model, we estimate changes in the number of heat-related deaths in 2050 resulting from modifications to vegetative cover and surface albedo across three climatically and demographically diverse US metropolitan areas: Atlanta, Georgia, Philadelphia, Pennsylvania, and Phoenix, Arizona. Employing separate health impact functions for average warm season and heat wave conditions in 2050, we find combinations of vegetation and albedo enhancement to offset projected increases in heat-related mortality by 40 to 99% across the three metropolitan regions. These results demonstrate the potential for extensive land surface changes in cities to provide adaptive benefits to urban populations at risk for rising heat exposure with climate change. PMID:24964213

  1. Adaptation to an autoimmune disorder: Does mental flexibility impact illness-related self-regulation?

    PubMed

    Karademas, Evangelos C; Ktistaki, Georgia; Dimitraki, Georgia; Papastefanakis, Emmanouil; Kougkas, Nikolaos; Fanouriakis, Antonios; Gergianaki, Irini; Bertsias, George; Sidiropoulos, Prodromos; Simos, Panagiotis

    2016-01-01

    To examine whether mental flexibility moderates the relationship between illness representations of control and coping behaviour in individuals suffering from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recently, diagnosed RA (N = 80) and SLE (N = 75) patients completed questionnaires about illness representations of personal and treatment control and four coping behaviours: instrumental coping, adherence to medical advice, palliative coping and wishful thinking. Mental flexibility was assessed with the Trail Making Test Part B (TMT-B), while visuomotor processing speed, as a confounder, was assessed with the Trail Making Test Part A (TMT-A). Moderated mediation models were tested within a bootstrapped multiple regression framework. TMT-A scores had no statistically significant moderation effects on the relation between representations and coping behaviour. Conversely, in those participants with SLE, TMT-B scores moderated the relation of personal control to wishful thinking and palliative coping, as well as the relation of treatment control to both wishful thinking and palliative coping. All significant effects were restricted to the SLE group. Interactions between neurocognitive factors and the process of illness adaptation may emerge early during the course of SLE. The present findings highlight the role of cognitive functioning as an integral part of the illness-related self-regulation mechanism.

  2. Avoided heat-related mortality through climate adaptation strategies in three US cities.

    PubMed

    Stone, Brian; Vargo, Jason; Liu, Peng; Habeeb, Dana; DeLucia, Anthony; Trail, Marcus; Hu, Yongtao; Russell, Armistead

    2014-01-01

    Heat-related mortality in US cities is expected to more than double by the mid-to-late 21st century. Rising heat exposure in cities is projected to result from: 1) climate forcings from changing global atmospheric composition; and 2) local land surface characteristics responsible for the urban heat island effect. The extent to which heat management strategies designed to lessen the urban heat island effect could offset future heat-related mortality remains unexplored in the literature. Using coupled global and regional climate models with a human health effects model, we estimate changes in the number of heat-related deaths in 2050 resulting from modifications to vegetative cover and surface albedo across three climatically and demographically diverse US metropolitan areas: Atlanta, Georgia, Philadelphia, Pennsylvania, and Phoenix, Arizona. Employing separate health impact functions for average warm season and heat wave conditions in 2050, we find combinations of vegetation and albedo enhancement to offset projected increases in heat-related mortality by 40 to 99% across the three metropolitan regions. These results demonstrate the potential for extensive land surface changes in cities to provide adaptive benefits to urban populations at risk for rising heat exposure with climate change.

  3. Work-Related Stress Risk Assessment in Italy: A Methodological Proposal Adapted to Regulatory Guidelines

    PubMed Central

    Persechino, Benedetta; Valenti, Antonio; Ronchetti, Matteo; Rondinone, Bruna Maria; Di Tecco, Cristina; Vitali, Sara; Iavicoli, Sergio

    2013-01-01

    Background Work-related stress is one of the major causes of occupational ill health. In line with the regulatory framework on occupational health and safety (OSH), adequate models for assessing and managing risk need to be identified so as to minimize the impact of this stress not only on workers' health, but also on productivity. Methods After close analysis of the Italian and European reference regulatory framework and work-related stress assessment and management models used in some European countries, we adopted the UK Health and Safety Executive's (HSE) Management Standards (MS) approach, adapting it to the Italian context in order to provide a suitable methodological proposal for Italy. Results We have developed a work-related stress risk assessment strategy, meeting regulatory requirements, now available on a specific web platform that includes software, tutorials, and other tools to assist companies in their assessments. Conclusion This methodological proposal is new on the Italian work-related stress risk assessment scene. Besides providing an evaluation approach using scientifically validated instruments, it ensures the active participation of occupational health professionals in each company. The assessment tools provided enable companies not only to comply with the law, but also to contribute to a database for monitoring and assessment and give access to a reserved area for data analysis and comparisons. PMID:23961332

  4. The Relations of Employability Skills to Career Adaptability among Technical School Students

    ERIC Educational Resources Information Center

    de Guzman, Allan B.; Choi, Kyoung Ok

    2013-01-01

    This two pronged study reports the initial validation of the psychometric properties and factor structure of the Career Adapt-Abilities Scale (CAAS) in the context of Papua New Guinea (PNG) and the investigation of the relationship between employability skills and career adaptability. Results of the study revealed that CAAS can be a valid and…

  5. THE RELATION OF ENZYMATIC ADAPTATION TO THE METABOLISM OF ENDOGENOUS AND EXOGENOUS SUBSTRATES

    PubMed Central

    Spiegelman, S.; Reiner, John M.; Cohnberg, Rosellen

    1947-01-01

    The source of energy for enzymatic adaptation has been investigated. Aerobically, it is found that the endogenous carbohydrate reserves may be used as such a source. In cells depleted of their reserves, the adaptive substrate itself can be oxidized even while it cannot be fermented, and so can serve as a source of energy for the adaptation to a fermentative mode of utilization. Anaerobically, adaptation may occur at the expense of stored energy-rich compounds, while the reserves and the adaptive substrate are now useless as fuel. Such compounds appear to be more plentiful in young than in old cells. The addition of any fermentable substrate, such as glucose, leads to rapid anaerobic adaptation. Experiments in which maltose-adapted cells are adapted anaerobically to galactose with the aid of a little added maltose, and conversely, show that fermentability is the criterion of usefulness for an exogenous substrate in aiding the adaptive process. None of the endogenous and exogenous energy sources which have been investigated will facilitate adaptation unless the adaptive substrate is present while they are being consumed. The significance of these findings and the adequacy of "activation" hypotheses to explain enzymatic adaptation has been discussed. PMID:19873518

  6. The Relations of Employability Skills to Career Adaptability among Technical School Students

    ERIC Educational Resources Information Center

    de Guzman, Allan B.; Choi, Kyoung Ok

    2013-01-01

    This two pronged study reports the initial validation of the psychometric properties and factor structure of the Career Adapt-Abilities Scale (CAAS) in the context of Papua New Guinea (PNG) and the investigation of the relationship between employability skills and career adaptability. Results of the study revealed that CAAS can be a valid and…

  7. XPC INITIATION CODON MUTATION IN XERODERMA PIGMENTOSUM PATIENTS WITH AND WITHOUT NEUROLOGICAL SYMPTOMS

    PubMed Central

    Khan, Sikandar G.; Oh, Kyu-Seon; Emmert, Steffen; Imoto, Kyoko; Tamura, Deborah; DiGiovanna, John J.; Shahlavi, Tala; Armstrong, Najealicka; Baker, Carl C.; Neuburg, Marcy; Zalewski, Chris; Brewer, Carmen; Wiggs, Edythe; Schiffmann, Raphael; Kraemer, Kenneth H.

    2008-01-01

    Two unrelated xeroderma pigmentosum (XP) patients, with and without neurological abnormalities respectively, had identical defects in the XPC DNA nucleotide excision repair (NER) gene. Patient XP21BE, a 27 y/o woman, had developmental delay and early onset of sensorineural hearing loss. In contrast, patient XP329BE, a 13 y/o boy, had a normal neurological examination. Both patients had marked lentiginous hyperpigmentation and multiple skin cancers at an early age. Their cultured fibroblasts showed similar hypersensitivity to killing by UV and reduced repair of DNA photoproducts. Cells from both patients had a homozygous c.2T>G mutation in the XPC gene which changed the ATG initiation codon to arginine. Both had low levels of XPC message and no detectable XPC protein on Western blotting. There was no functional XPC activity in both as revealed by the failure of localization of XPC and other NER proteins at the sites of UV-induced DNA in a sensitive in vivo immunofluorescence assay. XPC cDNA containing the initiation codon mutation was functionally inactive in a post-UV host cell reactivation assay. Microsatellite markers flanking the XPC gene showed only a small region of identity (~30kBP), indicating that the patients were not closely related. Thus, the initiation codon mutation resulted in DNA repair deficiency in cells from both patients and greatly increased cancer susceptibility. The neurological abnormalities in patient XP21BE may be related to close consanguinity and simultaneous inheritance of other recessive genes or other gene modifying effects rather than the influence of XPC gene itself. PMID:18955168

  8. Codon usage in mammalian genes is biased by sequence slippage mechanisms.

    PubMed

    Bains, W

    1993-01-01

    The codons for some conserved amino acids are found to be the same between homologous genes from different species when the statistics of codon usage would suggest that they should be different. I examine whether this 'coincidence' of codon usage could be due to genetic mechanisms homogenising the DNA around specific sites. This paper describes the further analysis of the coincident codons in 19 genes (a total of 96 homologues) for slippage. Coincident codons arise in contexts of increased sequence simplicity, and have a high chance of occurring within sequences similar to the recombination-prone minisatellite 'core' sequence. This suggests a role of genetic homogenisation in their generation.

  9. Global adaptation to a lipid environment triggers the dormancy-related phenotype of Mycobacterium tuberculosis.

    PubMed

    Rodríguez, Juan G; Hernández, Adriana C; Helguera-Repetto, Cecilia; Aguilar Ayala, Diana; Guadarrama-Medina, Rosalina; Anzóla, Juan M; Bustos, Jose R; Zambrano, María M; González-Y-Merchand, Jorge; García, María J; Del Portillo, Patricia

    2014-05-20

    Strong evidence supports the idea that fatty acids rather than carbohydrates are the main energy source of Mycobacterium tuberculosis during infection and latency. Despite that important role, a complete scenario of the bacterium's metabolism when lipids are the main energy source is still lacking. Here we report the development of an in vitro model to analyze adaptation of M. tuberculosis during assimilation of long-chain fatty acids as sole carbon sources. The global lipid transcriptome revealed a shift toward the glyoxylate cycle, the overexpression of main regulators whiB3, dosR, and Rv0081, and the increased expression of several genes related to reductive stress. Our evidence showed that lipid storage seems to be the selected mechanism used by M. tuberculosis to ameliorate the assumed damage of reductive stress and that concomitantly the bacilli acquired a slowed-growth and drug-tolerant phenotype, all characteristics previously associated with the dormant stage. Additionally, intergenic regions were also detected, including the unexpected upregulation of tRNAs that suggest a new role for these molecules in the acquisition of a drug-tolerant phenotype by dormant bacilli. Finally, a set of lipid signature genes for the adaptation process was also identified. This in vitro model represents a suitable condition to illustrate the participation of reductive stress in drugs' activity against dormant bacilli, an aspect scarcely investigated to date. This approach provides a new perspective to the understanding of latent infection and suggests the participation of previously undetected molecules. Mycobacterium tuberculosis establishes long-lasting highly prevalent infection inside the human body, called latent tuberculosis. The known involvement of fatty acids is changing our understanding of that silent infection; however, question of how tubercle bacilli globally adapt to a lipid-enriched environment is still an unanswered. With the single change of providing fatty

  10. Adaptive relative pose control for autonomous spacecraft rendezvous and proximity operations with thrust misalignment and model uncertainties

    NASA Astrophysics Data System (ADS)

    Sun, Liang; Zheng, Zewei

    2017-04-01

    An adaptive relative pose control strategy is proposed for a pursue spacecraft in proximity operations on a tumbling target. Relative position vector between two spacecraft is required to direct towards the docking port of the target while the attitude of them must be synchronized. With considering the thrust misalignment of pursuer, an integrated controller for relative translational and relative rotational dynamics is developed by using norm-wise adaptive estimations. Parametric uncertainties, unknown coupled dynamics, and bounded external disturbances are compensated online by adaptive update laws. It is proved via Lyapunov stability theory that the tracking errors of relative pose converge to zero asymptotically. Numerical simulations including six degrees-of-freedom rigid body dynamics are performed to demonstrate the effectiveness of the proposed controller.

  11. Adapting an Evidence-Based Intervention to Address Targeted Therapy-Related Fatigue in Chronic Myeloid Leukemia Patients.

    PubMed

    Poort, Hanneke; Meade, Cathy D; Knoop, Hans; Gielissen, Marieke F M; Pinilla-Ibarz, Javier; Jacobsen, Paul B

    2016-11-08

    Fatigue is one of the most important quality of life issues experienced by patients being treated with oral targeted therapy for chronic myeloid leukemia (CML). However, no intervention exists that specifically addresses strategies to reduce targeted therapy-related fatigue. This study adapted an evidence-based clinic-delivered intervention (EBI) "cognitive behavior therapy for post-cancer fatigue" for use in CML patients. The existing EBI was based on 6 established perpetuating factors of fatigue (ie, sleep, activity, helpful thinking, coping with cancer, social support, and fear of disease recurrence). Study aims were to gauge reactions to (1) existing content and (2) a new Internet-assisted intervention delivery format. Guided by the ADAPT-ITT framework, we used a series of systematic steps and adaptation methodologies, including semistructured interviews with CML patients and providers and feedback from topical experts. Patients were receptive to existing content topics and an Internet-assisted delivery format was acceptable. A key theme reflected the need for a new customized psychoeducational module about CML as a disease and its treatment. Both providers and patients held positive views about the potential of the adapted EBI to improve fatigue. Findings offered essential guidance for the adaptation and reinforced the utility of the adapted intervention. Adapting existing EBIs for new audiences contributes to advancing findings of evidence-based research, ultimately providing nurses and other healthcare providers with important referral options to interventions that may provide useful strategies to improve quality of life and reduce targeted therapy-related fatigue.

  12. Species-Specific Codon Context Rules Unveil Non-Neutrality Effects of Synonymous Mutations

    PubMed Central

    Moura, Gabriela R.; Pinheiro, Miguel; Freitas, Adelaide; Oliveira, José L.; Frommlet, Jörg C.; Carreto, Laura; Soares, Ana R.; Bezerra, Ana R.; Santos, Manuel A. S.

    2011-01-01

    Background Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution. Methodologies/Principal Findings Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases. Conclusions Since in vivo studies provide evidence for a role of codon context on decoding fidelity in E. coli and for decoding efficiency in mammalian cells, our data support the hypothesis that, like codon usage, codon context modulates the evolution of gene primary structure and fine tunes the structure of open reading frames for high genome translational fidelity and efficiency in the 3 domains of life. PMID:22046369

  13. Compromised respiratory adaptation and thermoregulation in aging and age-related diseases.

    PubMed

    Chan, Sic L; Wei, Zelan; Chigurupati, Srinivasulu; Tu, Weihong

    2010-01-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) production are at the heart of the aging process and are thought to underpin age-related diseases. Mitochondria are not only the primary energy-generating system but also the dominant cellular source of metabolically derived ROS. Recent studies unravel the existence of mechanisms that serve to modulate the balance between energy metabolism and ROS production. Among these is the regulation of proton conductance across the inner mitochondrial membrane that affects the efficiency of respiration and heat production. The field of mitochondrial respiration research has provided important insight into the role of altered energy balance in obesity and diabetes. The notion that respiration and oxidative capacity are mechanistically linked is making significant headway into the field of aging and age-related diseases. Here we review the regulation of cellular energy and ROS balance in biological systems and survey some of the recent relevant studies that suggest that respiratory adaptation and thermodynamics are important in aging and age-related diseases.

  14. Biomarkers for assessing population and individual health and disease related to stress and adaptation.

    PubMed

    McEwen, Bruce S

    2015-03-01

    Biomarkers are important in stress biology in relation to assessing individual and population health. They facilitate tapping meaningfully into the complex, non-linear interactions that affect the brain and multiple systems of the body and promote adaptation or, when dysregulated, they can accelerate disease processes. This has demanded a multifactorial approach to the choice of biomarkers. This is necessary in order to adequately describe and predict how an individual embedded in a particular social and physical environment, and with a unique genotype and set of lifetime experiences, will fare in terms of health and disease risk, as well as how that individual will respond to an intervention. Yet, at the same time, single biomarkers can have a predictive or diagnostic value when combined with carefully designed longitudinal assessment of behavior and disease related to stress. Moreover, the methods of brain imaging, themselves the reflection of the complexity of brain functional architecture, have provided new ways of diagnosing, and possibly differentiating, subtypes of depressive illness and anxiety disorders that are precipitated or exacerbated by stress. Furthermore, postmortem assessment of brain biomarkers provides important clues about individual vulnerability for suicide related to depression and this may lead to predictive biomarkers to better treat individuals with suicidal depression. Once biomarkers are available, approaches to prevention and treatment should take advantage of the emerging evidence that activating brain plasticity together with targeted behavioral interventions is a promising strategy.

  15. Adapting relative phase of bimanual isometric force coordination through scaling visual information intermittency.

    PubMed

    Lafe, Charley W; Pacheco, Matheus M; Newell, Karl M

    2016-06-01

    Visual information plays an adaptive role in the relation between bimanual force coupling and error corrective processes of isometric force control. In the present study, the evolving distribution of the relative phase properties of bimanual isometric force coupling was examined by scaling within a trial the temporal feedback rate of visual intermittency (short to long presentation intervals and vice versa). The force error (RMSE) was reduced, and time-dependent irregularity (SampEn) of the force output was increased with greater amounts of visual information (shorter intermittency). Multi-stable coordination patterns of bimanual isometric force control were differentially shifted toward and away from the intrinsic dynamics by the changing the intermittency of visual information. The distribution of Hilbert transformed relative phase values showed progressively a predominantly anti-phase mode under less intermittent visual information to predominantly an in-phase mode with limited (almost no) visual information. Correlation between the hands showed a continuous reduction, rather than abrupt "transition," with increase in visual information, although no mean negative correlation was realized, despite the tendency towards an anti-phase distribution. Lastly, changes in both the performance outcome and bimanual isometric force coordination occurred at visual feedback rates faster than the minimal visual processing times established from single limb movement and isometric force protocols. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  17. Putative mitochondrial polypeptides coded by expanded quadruplet codons, decoded by antisense tRNAs with unusual anticodons.

    PubMed

    Seligmann, Hervé

    2012-11-01

    Weak triplet codon-anticodon interactions render ribosome-free translation unlikely. Some modern tRNAs read quadruplet codons (tetracodons), suggesting vestigial ribosome-free translation. Here, mitochondrial genomes are explored for tetracoded overlapping protein coding (tetra)genes. Occasional single tetracodons within regular mitochondrial genes coevolve positively/negatively with antisense tRNAs with predicted reduced/expanded anticodons (depending on taxon), suggesting complex tetra-decoding mechanisms. Transcripts of antisense tRNAs with unusual anticodons are more abundant than of homologues with regular anticodons. Assuming overlapping tetracoding with silent 4th tetracodon position, BLAST aligns 10 putative tetragenes spanning 17% of regular human mitochondrial protein coding tricodons with 14 GenBank proteins. Various tests including predicted peptide secondary structures, 3rd codon position (of the regular main frame of the protein coding gene) conservation against replicational deamination mutation gradients, and circular code usage (overlapping genes avoid using circular code codons) confirm tetracoding in these overlapping tetragenes with silent 4th position, but not for BLAST-predicted tetragenes assuming silent 2nd or 3rd positions. This converges with tetradecoding mechanisms that are more compatible with silent 4th, than at other, tetracodon positions. Tetracoding increases with (a) GC-contents, perhaps conserved or switched on in high temperature conditions; (b) usage of theoretically predicted 'tessera' tetracodons; (c) 12s rRNA stability; and d) antisense tRNA numbers with predicted expanded anticodons. Most detected tetragenes are not evolutionarily conserved, apparently reflect specific, transient adaptations. Tetracoding increases with mammal longevity.

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2016-08-01

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

  20. Impairments in Dark Adaptation are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen

    PubMed Central

    Flamendorf, J; Agrón, E; Wong, WT; Thompson, D; Wiley, HE; Doss, EL; Al-Holou, S; Ferris, FL; Chew, EY; Cukras, C

    2015-01-01

    Purpose We investigate whether ocular and person-based characteristics are associated with dark adaptation (DA) measured using the AdaptRx™ device (Apeliotus Technologies, Atlanta, GA). Design Cross-sectional, single-center, observational study. Participants 116 participants >50 years with a range in age-related macular degeneration (AMD) severity. Methods Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and confirmed with OCT. Eyes were also graded for AMD features (drusen, pigmentary changes, late AMD) to generate a person-based AMD severity groups. One eye was designated the study eye for DA testing using the AdaptRx™ device. Nonparametric statistical testing was performed on all comparisons. Main Outcome Measure The primary outcome of this study was the rod-intercept time (RIT) which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5 × 10−3 cd/m2 (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. Results A total of 116 study eyes in 116 participants (mean age=75.4±9.4 years, 58% female) were analyzed. Increased RIT was significantly associated with increasing age (r=0.34, p=0.0002), decreasing BCVA (r=−0.54, p<0.0001), pseudophakia (p=0.03), decreasing subfoveal choroidal thickness (r=−0.27, p=0.003). Study eyes with RPD (15/116, 13%) had a significantly greater mean RIT compared to eyes without RPD in any AMD severity group (p<0.02 for all comparisons) with 80% reaching the DA test ceiling. Conclusion Impairments in DA increase with age, worse visual acuity, presence of RPD, AMD severity and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariable model that best fit our data included age, AMD group, and presence of RPD (R2=0.56) with the presence of RPD conferring the

  1. Global Adaptation to a Lipid Environment Triggers the Dormancy-Related Phenotype of Mycobacterium tuberculosis

    PubMed Central

    Rodríguez, Juan G.; Hernández, Adriana C.; Helguera-Repetto, Cecilia; Aguilar Ayala, Diana; Guadarrama-Medina, Rosalina; Anzóla, Juan M.; Bustos, Jose R.; Zambrano, María M.; González-y-Merchand, Jorge

    2014-01-01

    ABSTRACT Strong evidence supports the idea that fatty acids rather than carbohydrates are the main energy source of Mycobacterium tuberculosis during infection and latency. Despite that important role, a complete scenario of the bacterium’s metabolism when lipids are the main energy source is still lacking. Here we report the development of an in vitro model to analyze adaptation of M. tuberculosis during assimilation of long-chain fatty acids as sole carbon sources. The global lipid transcriptome revealed a shift toward the glyoxylate cycle, the overexpression of main regulators whiB3, dosR, and Rv0081, and the increased expression of several genes related to reductive stress. Our evidence showed that lipid storage seems to be the selected mechanism used by M. tuberculosis to ameliorate the assumed damage of reductive stress and that concomitantly the bacilli acquired a slowed-growth and drug-tolerant phenotype, all characteristics previously associated with the dormant stage. Additionally, intergenic regions were also detected, including the unexpected upregulation of tRNAs that suggest a new role for these molecules in the acquisition of a drug-tolerant phenotype by dormant bacilli. Finally, a set of lipid signature genes for the adaptation process was also identified. This in vitro model represents a suitable condition to illustrate the participation of reductive stress in drugs’ activity against dormant bacilli, an aspect scarcely investigated to date. This approach provides a new perspective to the understanding of latent infection and suggests the participation of previously undetected molecules. PMID:24846381

  2. Age-related differences in pelvic and trunk motion and gait adaptability at different walking speeds.

    PubMed

    Gimmon, Yoav; Riemer, Raziel; Rashed, Hisham; Shapiro, Amir; Debi, Ronen; Kurz, Ilan; Melzer, Itshak

    2015-10-01

    This study aimed at investigating age-related changes in gait kinematics and in kinematic adaptations over a wide range of walking velocities. Thirty-four older adults and 14 younger adults walked on a treadmill; the treadmill velocity was gradually increased in increments of 0.2miles/hour (mph) (1.1-1.9mph) and then decreased in the same increments. Pelvic, trunk, upper limbs and lower limbs angular total ranges of motion (tROM), stride time, stride length, and step width were measured. The older adults had lower pelvic, trunk tROM and shorter strides and stride time compared with the younger adults. As the treadmill speed was gradually increased, the older adults showed an inability to change the pelvic list angular motions (3.1±1.3° to 3.2±1.4°) between different walking velocities, while the younger adults showed changes (5.1±1.8° to 6.3±1.7°) as a function of the walking velocity. As the walking velocity increased, the older adults increased their stride length (from 57.0±10cm to 90.2±0.1cm) yet stride times remained constant (from 1.17±0.3sec to 1.08±0.1sec), while the younger adults increased stride length and reduced stride times (from 71.4±10cm to 103.0±7.9m and from 1.45±0.2sec to 1.22±0.1sec, respectively). In conclusion, the older adults were unable to make adaptations in pelvic and trunk kinematics between different walking speeds (rigid behavior), while the younger adults showed more flexible behavior. Pelvic and trunk kinematics in different walking speeds can be used as variables in the assessment of gait in older adults.

  3. Adaptation to illness in relation to pain perceived by patients after surgery

    PubMed Central

    Chabowski, Mariusz; Junke, Michał; Juzwiszyn, Jan; Milan, Magdalena; Malinowski, Maciej; Janczak, Dariusz

    2017-01-01

    Background Pain is one of the factors that decrease quality of life. Undergoing surgery is inevitably associated with the sensation of pain, which can affect a patient’s level of acceptance of an illness. The aim of the study was to evaluate the level of acceptance of illness in patients undergoing surgical treatment with relation to the pain perceived by them during surgical treatment and to determine other factors that affect adaptation to illness among patients subjected to invasive treatment. Material and methods The study was conducted on a group of 100 patients with mean age of 51.27 (SD=18.98) hospitalized in surgery departments in the Provincial Specialist Hospital in Wrocław, Poland, in April 2016. The Acceptance of Illness Scale (AIS) and the Visual Analog Scale (VAS) for pain were used. Results The mean score of VAS was 3.86 (SD =2.02). The mean score of AIS was 24.42 (SD =7.35). The level of acceptance of illness was significantly negatively correlated with the intensity of pain (p<0.001; r=−0.498), the number of coexisting diseases (p=0.002; r=−0.31), age (p<0.001; r=−0.391), and the period of time since the operation (p=0.007; r=−0.266). Patients taking analgesics showed a significantly lower acceptance of illness than those who did not (p=0.009). A patient’s place of living, education, and sex had no significant impact on their acceptance of illness. Conclusion A higher level of pain translates into a lower adaptation to illness despite the use of analgesics, which may indicate that inadequate pain control leads to a decrease in the acceptance of illness. Further research on monitoring postoperative pain, as well as the development of postoperative prevention programs, is required. PMID:28721086

  4. US/Japan workshop on mitigation and adaptation technologies related to global climate change

    SciTech Connect

    Bernthal, F.M.

    1993-12-31

    It is a great pleasure for me to have the honor of delivering the keynote address for this important gathering, an honor enhanced further because of the many activities and historic relationships represented by this workshop. First of all, it represents the spirit of continuing cooperation and good relations between the United States and Japan. With the aid of the framework provided by the U.S./Japan Science and Technology Agreement, our two nations can come together to address a problem that has no national boundaries {hor_ellipsis} and we can think about solutions of potential benefit to all citizens of the global community. This workshop also symbolizes the spirit of cooperation so characteristic of the conduct of research in science and technology -- cooperation between us as individual scientists and engineers, between the various institutions we represent, and across our diverse disciplines. This workshop is only the second of its kind. The first US/Japan Workshop on global climate change was held last year in Japan. That workshop focused on cooperative scientific research in the United States and Japan. Out of it came a general agreement to continue collaborative work and to extend cooperation into the area of global change-related technologies, in particular those technologies that hold promise for mitigation and adaptation.

  5. Testing the Relative Performance of Data Adaptive Prediction Algorithms: A Generalized Test of Conditional Risk Differences

    PubMed Central

    Polley, Eric C.; Briggs, Farren B. S.; van der Laan, Mark J.; Hubbard, Alan

    2016-01-01

    Comparing the relative fit of competing models can be used to address many different scientific questions. In classical statistics one can, if appropriate, use likelihood ratio tests and information based criterion, whereas clinical medicine has tended to rely on comparisons of fit metrics like C-statistics. However, for many data adaptive modelling procedures such approaches are not suitable. In these cases, statisticians have used cross-validation, which can make inference challenging. In this paper we propose a general approach that focuses on the “conditional” risk difference (conditional on the model fits being fixed) for the improvement in prediction risk. Specifically, we derive a Wald-type test statistic and associated confidence intervals for cross-validated test sets utilizing the independent validation within cross-validation in conjunction with a test for multiple comparisons. We show that this test maintains proper Type I Error under the null fit, and can be used as a general test of relative fit for any semi-parametric model alternative. We apply the test to a candidate gene study to test for the association of a set of genes in a genetic pathway. PMID:26529567

  6. Nucleotide diversity patterns of local adaptation at drought-related candidate genes in wild tomatoes.

    PubMed

    Xia, Hui; Camus-Kulandaivelu, Létizia; Stephan, Wolfgang; Tellier, Aurélien; Zhang, Zhenwen

    2010-10-01

    We surveyed nucleotide diversity at two candidate genes LeNCED1 and pLC30-15, involved in an ABA (abscisic acid) signalling pathway, in two closely related tomato species Solanum peruvianum and Solanum chilense. Our six population samples (three for each species) cover a range of mesic to very dry habitats. The ABA pathway plays an important role in the plants' response to drought stress. LeNCED1 is an upstream gene involved in ABA biosynthesis, and pLC30-15 is a dehydrin gene positioned downstream in the pathway. The two genes show very different patterns of nucleotide variation. LeNCED1 exhibits very low nucleotide diversity relative to the eight neutral reference loci that were previously surveyed in these populations. This suggests that strong purifying selection has been acting on this gene. In contrast, pLC30-15 exhibits higher levels of nucleotide diversity and, in particular in S. chilense, higher genetic differentiation between populations than the reference loci, which is indicative of local adaptation. In the more drought-tolerant species S. chilense, one population (from Quicacha) shows a significant haplotype structure, which appears to be the result of positive (diversifying) selection.

  7. Adaptive and maladaptive components of rumination? Diagnostic specificity and relation to depressive biases.

    PubMed

    Joormann, Jutta; Dkane, Marco; Gotlib, Ian H

    2006-09-01

    The present study investigated the validity of the two-factor solution of items selected from the Rumination Scale of the Response Style Questionnaire proposed by Treynor, Gonzalez, and Nolen-Hoeksema (2003). In the first part of this study we used samples of currently depressed (MDD), formerly depressed (FD), socially anxious (SP), and healthy control participants to examine whether the brooding and reflective pondering components differentiate participants with an anxiety disorder from participants with depression. In the second part of this study we examined whether these components of rumination were differentially related to cognitive biases in depression. Overall, the MDD group exhibited higher brooding scores than did all other groups; SP and FD groups did not differ from each other but obtained higher brooding scores than did the control participants. Only the MDD and the control groups differed on the reflective pondering factor. Importantly, brooding and reflective pondering were differentially related to cognitive biases. Specifically, the correlation between brooding/reflective pondering and memory bias was not significant when depressive symptoms were partialed out. The correlation between brooding and attentional bias for sad faces, however, remained significant even when current depressive symptoms were taken into account. In sum, our results support the formulation that rumination is composed of an adaptive reflective pondering factor and a maladaptive brooding factor.

  8. Learning from experience: Event-related potential correlates of reward processing, neural adaptation, and behavioral choice

    PubMed Central

    Walsh, Matthew M.; Anderson, John R.

    2012-01-01

    To behave adaptively, we must learn from the consequences of our actions. Studies using event-related potentials (ERPs) have been informative with respect to the question of how such learning occurs. These studies have revealed a frontocentral negativity termed the feedback-related negativity (FRN) that appears after negative feedback. According to one prominent theory, the FRN tracks the difference between the values of actual and expected outcomes, or reward prediction errors. As such, the FRN provides a tool for studying reward valuation and decision making. We begin this review by examining the neural significance of the FRN. We then examine its functional significance. To understand the cognitive processes that occur when the FRN is generated, we explore variables that influence its appearance and amplitude. Specifically, we evaluate four hypotheses: (1) the FRN encodes a quantitative reward prediction error; (2) the FRN is evoked by outcomes and by stimuli that predict outcomes; (3) the FRN and behavior change with experience; and (4) the system that produces the FRN is maximally engaged by volitional actions. PMID:22683741

  9. Adaptation study of the Turkish version of the Gambling-Related Cognitions Scale (GRCS-T).

    PubMed

    Arcan, K; Karanci, A N

    2015-03-01

    This study aimed to adapt and to test the validity and the reliability of the Turkish version of the Gambling-Related Cognitions Scale (GRCS-T) that was developed by Raylu and Oei (Addiction 99(6):757-769, 2004a). The significance of erroneous cognitions in the development and the maintenance of gambling problems, the importance of promoting gambling research in different cultures, and the limited information about the gambling individuals in Turkey due to limited gambling research interest inspired the present study. The sample consisted of 354 voluntary male participants who were above age 17 and betting on sports and horse races selected through convenience sampling in betting terminals. The results of the confirmatory factor analysis following the original scale's five factor structure indicated a good fit for the data. The analyses were carried out with 21 items due to relatively inadequate psychometric properties of two GRCS-T items. Correlational analyses and group comparison tests supported the concurrent and the criterion validity of the GRCS-T. Cronbach's alpha coefficient for the whole scale was 0.84 whereas the coefficients ranged between 0.52 and 0.78 for the subscales of GRCS-T. The findings suggesting that GRCS-T is a valid and reliable instrument to identify gambling cognitions in Turkish samples are discussed considering the possible influence of the sample make-up and cultural texture within the limitations of the present study and in the light of the relevant literature.

  10. Experimental demonstration of single-mode fiber coupling over relatively strong turbulence with adaptive optics.

    PubMed

    Chen, Mo; Liu, Chao; Xian, Hao

    2015-10-10

    High-speed free-space optical communication systems using fiber-optic components can greatly improve the stability of the system and simplify the structure. However, propagation through atmospheric turbulence degrades the spatial coherence of the signal beam and limits the single-mode fiber (SMF) coupling efficiency. In this paper, we analyze the influence of the atmospheric turbulence on the SMF coupling efficiency over various turbulences. The results show that the SMF coupling efficiency drops from 81% without phase distortion to 10% when phase root mean square value equals 0.3λ. The simulations of SMF coupling with adaptive optics (AO) indicate that it is inevitable to compensate the high-order aberrations for SMF coupling over relatively strong turbulence. The SMF coupling efficiency experiments, using an AO system with a 137-element deformable mirror and a Hartmann-Shack wavefront sensor, obtain average coupling efficiency increasing from 1.3% in open loop to 46.1% in closed loop under a relatively strong turbulence, D/r0=15.1.

  11. Natural reassignment of CUU and CUA sense codons to alanine in Ashbya mitochondria

    PubMed Central

    Ling, Jiqiang; Daoud, Rachid; Lajoie, Marc J.; Church, George M.; Söll, Dieter; Lang, B. Franz

    2014-01-01

    The discovery of diverse codon reassignment events has demonstrated that the canonical genetic code is not universal. Studying coding reassignment at the molecular level is critical for understanding genetic code evolution, and provides clues to genetic code manipulation in synthetic biology. Here we report a novel reassignment event in the mitochondria of Ashbya (Eremothecium) gossypii, a filamentous-growing plant pathogen related to yeast (Saccharomycetaceae). Bioinformatics studies of conserved positions in mitochondrial DNA-encoded proteins suggest that CUU and CUA codons correspond to alanine in A. gossypii, instead of leucine in the standard code or threonine in yeast mitochondria. Reassignment of CUA to Ala was confirmed at the protein level by mass spectrometry. We further demonstrate that a predicted is transcribed and accurately processed in vivo, and is responsible for Ala reassignment. Enzymatic studies reveal that is efficiently recognized by A. gossypii mitochondrial alanyl-tRNA synthetase (AgAlaRS). AlaRS typically recognizes the G3:U70 base pair of tRNAAla; a G3A change in Ashbya abolishes its recognition by AgAlaRS. Conversely, an A3G mutation in Saccharomyces cerevisiae confers tRNA recognition by AgAlaRS. Our work highlights the dynamic feature of natural genetic codes in mitochondria, and the relative simplicity by which tRNA identity may be switched. PMID:24049072

  12. Likelihood models of somatic mutation and codon substitution in cancer genes.

    PubMed Central

    Yang, Ziheng; Ro, Simon; Rannala, Bruce

    2003-01-01

    The role of somatic mutation in cancer is well established and several genes have been identified that are frequent targets. This has enabled large-scale screening studies of the spectrum of somatic mutations in cancers of particular organs. Cancer gene mutation databases compile the results of many studies and can provide insight into the importance of specific amino acid sequences and functional domains in cancer, as well as elucidate aspects of the mutation process. Past studies of the spectrum of cancer mutations (in particular genes) have examined overall frequencies of mutation (at specific nucleotides) and of missense, nonsense, and silent substitution (at specific codons) both in the sequence as a whole and in a specific functional domain. Existing methods ignore features of the genetic code that allow some codons to mutate to missense, or stop, codons more readily than others (i.e., by one nucleotide change, vs. two or three). A new codon-based method to estimate the relative rate of substitution (fixation of a somatic mutation in a cancer cell lineage) of nonsense vs. missense mutations in different functional domains and in different tumor tissues is presented. Models that account for several potential influences on rates of somatic mutation and substitution in cancer progenitor cells and allow biases of mutation rates for particular dinucleotide sequences (CGs and dipyrimidines), transition vs. transversion bias, and variable rates of silent substitution across functional domains (useful in detecting investigator sampling bias) are considered. Likelihood-ratio tests are used to choose among models, using cancer gene mutation data. The method is applied to analyze published data on the spectrum of p53 mutations in cancers. A novel finding is that the ratio of the probability of nonsense to missense substitution is much lower in the DNA-binding and transactivation domains (ratios near 1) than in structural domains such as the linker, tetramerization

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

    PubMed

    Carlini, David B; Makowski, Matthew

    2015-12-01

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

  14. Comparison of two codon optimization strategies to enhance recombinant protein production in Escherichia coli

    PubMed Central

    2011-01-01

    Background Variations in codon usage between species are one of the major causes affecting recombinant protein expression levels, with a significant impact on the economy of industrial enzyme production processes. The use of codon-optimized genes may overcome this problem. However, designing a gene for optimal expression requires choosing from a vast number of possible DNA sequences and different codon optimization methods have been used in the past decade. Here, a comparative study of the two most common methods is presented using calf prochymosin as a model. Results Seven sequences encoding calf prochymosin have been designed, two using the "one amino acid-one codon" method and five using a "codon randomization" strategy. When expressed in Escherichia coli, the variants optimized by the codon randomization approach produced significantly more proteins than the native sequence including one gene that produced an increase of 70% in the amount of prochymosin accumulated. On the other hand, no significant improvement in protein expression was observed for the variants designed with the one amino acid-one codon method. The use of codon-optimized sequences did not affect the quality of the recovered inclusion bodies. Conclusions The results obtained in this study indicate that the codon randomization method is a superior strategy for codon optimization. A significant improvement in protein expression was obtained for the largely established process of chymosin production, showing the power of this strategy to reduce production costs of industrial enzymes in microbial hosts. PMID:21371320

  15. Intragenic Spatial Patterns of Codon Usage Bias in Prokaryotic and Eukaryotic Genomes

    PubMed Central

    Qin, Hong; Wu, Wei Biao; Comeron, Josep M.; Kreitman, Martin; Li, Wen-Hsiung

    2004-01-01

    To study the roles of translational accuracy, translational efficiency, and the Hill-Robertson effect in codon usage bias, we studied the intragenic spatial distribution of synonymous codon usage bias in four prokaryotic (Escherichia coli, Bacillus subtilis, Sulfolobus tokodaii, and Thermotoga maritima) and two eukaryotic (Saccharomyces cerevisiae and Drosophila melanogaster) genomes. We generated supersequences at each codon position across genes in a genome and computed the overall bias at each codon position. By quantitatively evaluating the trend of spatial patterns using isotonic regression, we show that in yeast and prokaryotic genomes, codon usage bias increases along translational direction, which is consistent with purifying selection against nonsense errors. Fruit fly genes show a nearly symmetric M-shaped spatial pattern of codon usage bias, with less bias in the middle and both ends. The low codon usage bias in the middle region is best explained by interference (the Hill-Robertson effect) between selections at different codon positions. In both yeast and fruit fly, spatial patterns of codon usage bias are characteristically different from patterns of GC-content variations. Effect of expression level on the strength of codon usage bias is more conspicuous than its effect on the shape of the spatial distribution. PMID:15611189

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  17. Evidence of strain-mode-related cortical adaptation in the diaphysis of the horse radius.

    PubMed

    Mason, M W; Skedros, J G; Bloebaum, R D

    1995-09-01

    The relative importance that certain strain features, including mode (e.g., tension vs. compression) and magnitude, have in affecting adaptive bone remodeling seen in normal skeletally mature bones remains controversial. The equine radius is used as a model because in vivo strain data show that the mid-to-proximal diaphysis receives a consistent history of predominantly cranial-caudal bending loads, in contrast to the distal diaphysis which receives relatively more torsional loading superimposed on cranial-caudal bending. Medial and lateral cortices serve as control regions because they correspond to a neutral axis of bending. Equine radii were sectioned transversely at 65% (proximal), 50%, and 35% (distal) of length and cortical bone from the cranial ("tension"), caudal ("compression"), medial, and lateral regions was examined to determine if one, of many, structural and material features could be distinguished as being consistently related to the distribution of the prevailing strain modes. Mineral content (percent ash) differences, though statistically significant (p < 0.01), vary less than 1% between regions of the cortex at all sections. Porosity is not significantly different between any of the regions (p = 0.13). In the 65% and 50% sections, secondary osteon population density (OPD, osteons per square millimeter) and fractional area of secondary bone (FASB) are each nearly two times as great in the caudal regions than in the other three regions (p < 0.01). The 35% section shows a pattern opposite of that in the other sections--there are more than two times as many osteons in the cranial cortex than in the caudal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The Relation between Intellectual Functioning and Adaptive Behavior in the Diagnosis of Intellectual Disability

    ERIC Educational Resources Information Center

    Tassé, Marc J.; Luckasson, Ruth; Schalock, Robert L.

    2016-01-01

    Intellectual disability originates during the developmental period and is characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. In this article, we present a brief history of the diagnostic criteria of intellectual disability for both…

  19. The Mutual Adaptation Concept: Its Roots and Relatives. Documentation and Technical Assistance in Urban Schools.

    ERIC Educational Resources Information Center

    Meara, Hannah

    This paper explores the roots of the concept of mutual adaptation in the literature of cognitive psychology, anthropology, biology, organizational behavior, and policy analysis. It is said that while educational researchers use the concept, their neglect of the literature on it is due, in part, to contradictory definitions of mutual adaptation as…

  20. The Relation between Intellectual Functioning and Adaptive Behavior in the Diagnosis of Intellectual Disability

    ERIC Educational Resources Information Center

    Tassé, Marc J.; Luckasson, Ruth; Schalock, Robert L.

    2016-01-01

    Intellectual disability originates during the developmental period and is characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. In this article, we present a brief history of the diagnostic criteria of intellectual disability for both…

  1. Supporting adaptation decisions to address climate related impacts and hazards in the Caribbean (the CARIWIG project)

    NASA Astrophysics Data System (ADS)

    Burton, Aidan

    2015-04-01

    Managers and policy makers from regional and national institutions in the Caribbean require knowledge of the likely impacts and hazards arising from the present and future climate that are specific to their responsibility and geographical range, and relevant to their planning time-horizons. Knowledge, experience and the political support to develop appropriate adaptation strategies are also required. However, the climate information available for the region is of limited use as: observational records are intermittent and typically of short duration; climate model projections of the weather suffer from scale and bias issues; and statistical downscaling to provide locally relevant unbiased climate change information remains sporadic. Tropical cyclone activity is a considerable sporadic hazard in the region and yet related weather information is limited to historic events. Further, there is a lack of guidance for managers and policy makers operating with very limited resources to utilize such information within their remit. The CARIWIG project (June 2012 - May 2015) will be presented, reflecting on stakeholder impact, best practice and lessons learned. This project seeks to address the climate service needs of the Caribbean region through a combination of capacity building and improved provision of climate information services. An initial workshop with regional-scale stakeholders initiated a dialogue to develop a realistic shared vision of the needed information services which could be provided by the project. Capacity building is then achieved on a number of levels: knowledge and expertise sharing between project partners; raising understanding and knowledge of resources that support national and regional institutions' adaptation decisions; developing case studies in key sectors to test and demonstrate the information services; training for stakeholder technical staff in the use of the provided services; the development of a support network within and out

  2. Evolution of Synonymous Codon Usage in the Mitogenomes of Certain Species of Bilaterian Lineage with Special Reference to Chaetognatha

    PubMed Central

    Karumathil, Sudeesh; Dirisala, Vijaya R.; Srinadh, Uthpala; Nikhil, Valaboju; Kumar, N. Satya Sampath; Nair, Rahul R.

    2016-01-01

    Chaetognatha is a minor phylum, comprising transparent marine invertebrates varying in size from 0.5 to 12 cm. The exact phylogenetic position of Chaetognatha in Metazoa has not been deciphered as some embryological characteristics place chaetognaths among deuterostomes and some morphological characteristics place these among protostomes. In this study, the major factors that drive synonymous codon usage bias (SCUB) in the mitogenomes of representative species of Chaetognatha and chosen species of other closely related phyla were analyzed. Spearman’s rank correlation analyses of nucleotide contents suggested that mutational pressure and selection were acting in all examined mitogenomes but with varying intensities. The quantification of SCUB using effective number of codons vs. GC composition at the third codon position (GC3) plot suggested that mutational pressure due to GC compositional constraints might be one of the major influencing forces driving the SCUB in all chaetognaths except Sagitta enflata. However, neutrality plots revealed no significant correlation between GC3 and cumulative GC content at first and second codon positions (GC12) in all other species, except in Daphnia pulex. The parity rule 2 bias plot showed that significant compositional differences existed between C and G, as well as between A and T, contents in most of the protein-coding genes (PCGs) and, comparatively, A and T contents were used more proportionally than C and G contents in all chosen mitogenomes. Chi-square analysis revealed the presence of putative optimal codons in all species, except in S. enflata. The correspondence analysis identified that mutational pressure and selection act on the mitogenomes of the selected chaetognaths and other phyla with varying intensities. The cluster analysis based on relative synonymous codon usage (RSCU) values revealed that RSCU variations in the PCGs of mitogenomes of chaetognaths are more comparable with those of protostomes. Apart from

  3. The Enterobacterium Trabulsiella odontotermitis Presents Novel Adaptations Related to Its Association with Fungus-Growing Termites

    PubMed Central

    Gruntjes, Thijs; Otani, Saria; Estevez, James; da Costa, Rafael R.; Plunkett, Guy; Perna, Nicole T.; Poulsen, Michael

    2015-01-01

    Fungus-growing termites rely on symbiotic microorganisms to help break down plant material and to obtain nutrients. Their fungal cultivar, Termitomyces, is the main plant degrader and food source for the termites, while gut bacteria complement Termitomyces in the degradation of foodstuffs, fixation of nitrogen, and metabolism of amino acids and sugars. Due to the community complexity and because these typically anaerobic bacteria can rarely be cultured, little is known about the physiological capabilities of individual bacterial members of the gut communities and their associations with the termite host. The bacterium Trabulsiella odontotermitis is associated with fungus-growing termites, but this genus is generally understudied, with only two described species. Taking diverse approaches, we obtained a solid phylogenetic placement of T. odontotermitis among the Enterobacteriaceae, investigated the physiology and enzymatic profiles of T. odontotermitis isolates, determined the localization of the bacterium in the termite gut, compared draft genomes of two T. odontotermitis isolates to those of their close relatives, and examined the expression of genes relevant to host colonization and putative symbiont functions. Our findings support the hypothesis that T. odontotermitis is a facultative symbiont mainly located in the paunch compartment of the gut, with possible roles in carbohydrate metabolism and aflatoxin degradation, while displaying adaptations to association with the termite host, such as expressing genes for a type VI secretion system which has been demonstrated to assist bacterial competition, colonization, and survival within hosts. PMID:26162887

  4. Adaptation of hybrid human-computer interaction systems using EEG error-related potentials.

    PubMed

    Chavarriaga, Ricardo; Biasiucci, Andrea; Forster, Killian; Roggen, Daniel; Troster, Gerhard; Millan, Jose Del R

    2010-01-01

    Performance improvement in both humans and artificial systems strongly relies in the ability of recognizing erroneous behavior or decisions. This paper, that builds upon previous studies on EEG error-related signals, presents a hybrid approach for human computer interaction that uses human gestures to send commands to a computer and exploits brain activity to provide implicit feedback about the recognition of such commands. Using a simple computer game as a case study, we show that EEG activity evoked by erroneous gesture recognition can be classified in single trials above random levels. Automatic artifact rejection techniques are used, taking into account that subjects are allowed to move during the experiment. Moreover, we present a simple adaptation mechanism that uses the EEG signal to label newly acquired samples and can be used to re-calibrate the gesture recognition system in a supervised manner. Offline analysis show that, although the achieved EEG decoding accuracy is far from being perfect, these signals convey sufficient information to significantly improve the overall system performance.

  5. The Enterobacterium Trabulsiella odontotermitis Presents Novel Adaptations Related to Its Association with Fungus-Growing Termites.

    PubMed

    Sapountzis, Panagiotis; Gruntjes, Thijs; Otani, Saria; Estevez, James; da Costa, Rafael R; Plunkett, Guy; Perna, Nicole T; Poulsen, Michael

    2015-10-01

    Fungus-growing termites rely on symbiotic microorganisms to help break down plant material and to obtain nutrients. Their fungal cultivar, Termitomyces, is the main plant degrader and food source for the termites, while gut bacteria complement Termitomyces in the degradation of foodstuffs, fixation of nitrogen, and metabolism of amino acids and sugars. Due to the community complexity and because these typically anaerobic bacteria can rarely be cultured, little is known about the physiological capabilities of individual bacterial members of the gut communities and their associations with the termite host. The bacterium Trabulsiella odontotermitis is associated with fungus-growing termites, but this genus is generally understudied, with only two described species. Taking diverse approaches, we obtained a solid phylogenetic placement of T. odontotermitis among the Enterobacteriaceae, investigated the physiology and enzymatic profiles of T. odontotermitis isolates, determined the localization of the bacterium in the termite gut, compared draft genomes of two T. odontotermitis isolates to those of their close relatives, and examined the expression of genes relevant to host colonization and putative symbiont functions. Our findings support the hypothesis that T. odontotermitis is a facultative symbiont mainly located in the paunch compartment of the gut, with possible roles in carbohydrate metabolism and aflatoxin degradation, while displaying adaptations to association with the termite host, such as expressing genes for a type VI secretion system which has been demonstrated to assist bacterial competition, colonization, and survival within hosts.

  6. Evaluation of the field-adapted ADMA approach: absolute and relative energies of crambin and derivatives.

    PubMed

    Exner, Thomas E; Mezey, Paul G

    2005-12-21

    A large number of conformations and chemically modified variants of the protein crambin were used to extensively test the field-adapted adjustable density matrix assembler (FA-ADMA) method developed for ab initio quality quantum chemistry computations of proteins and other macromolecules, introduced in an earlier publication. In this method, the fuzzy density matrix fragmentation scheme of the original adjustable density matrix assembler (ADMA) method has been made more efficient by combining it with an approach of using point charges to approximate the effects of additional, distant parts of a given macromolecule in the quantum chemical calculation of each fragment. In this way, smaller parent molecules can be used for fragment generation, while achieving accuracy that can be obtained only with large parent molecules in the original ADMA method. Whereas in both methods the error relative to the Hartree-Fock result can be reduced below any threshold by choosing large enough parent molecules, this can be done more efficiently with the new method. In order to obtain reliable test results for the accuracy obtainable by the new method when compared to conventional Hartree-Fock calculations, we performed a large number of energy calculations for the protein crambin using various conformations available in the Protein Data Bank, various protonation states, and side chain mutations. Additionally, in order to test the performance of the method for protein-solvent interaction studies, the energy changes due to the formation of complexes with ethanol and single and multiple water molecules were investigated.

  7. Bony labyrinth morphometry indicates locomotor adaptations in the squirrel-related clade (Rodentia, Mammalia).

    PubMed

    Pfaff, Cathrin; Martin, Thomas; Ruf, Irina

    2015-06-22

    The semicircular canals (SCs) of the inner ear detect angular acceleration and are located in the bony labyrinth of the petrosal bone. Based on high-resolution computed tomography, we created a size-independent database of the bony labyrinth of 50 mammalian species especially rodents of the squirrel-related clade comprising taxa with fossorial, arboreal and gliding adaptations. Our sampling also includes gliding marsupials, actively flying bats, the arboreal tree shrew and subterranean species. The morphometric anatomy of the SCs was correlated to the locomotion mode. Even if the phylogenetic signal cannot entirely be excluded, the main significance for functional morphological studies has been found in the diameter of the SCs, whereas the radius of curvature is of minor interest. Additionally, we found clear differences in the bias angle of the canals between subterranean and gliding taxa, but also between sciurids and glirids. The sensitivity of the inner ear correlates with the locomotion mode, with a higher sensitivity of the SCs in fossorial species than in flying taxa. We conclude that the inner ear of flying and gliding mammals is less sensitive due to the large information flow into this sense organ during locomotion.

  8. Adapting to changing memory retrieval demands: evidence from event-related potentials.

    PubMed

    Benoit, Roland G; Werkle-Bergner, Markus; Mecklinger, Axel; Kray, Jutta

    2009-06-01

    This study investigated preparatory processes involved in adapting to changing episodic memory retrieval demands. Event-related potentials (ERPs) were recorded while participants performed a general old/new recognition task and a specific task that also required retrieval of perceptual details. The relevant task remained either constant or changed (predictably or randomly) across trials. Responses were slowed when participants switched from the specific to the general task but not vice versa. Hence, asymmetrical switch costs were observed, suggesting that retrieval preparation is dependent not only on the current retrieval goal but also influenced by recent retrieval attempts. Consistently, over posterior scalp regions ERPs associated with advance preparation were modulated by the preceding task, reflecting increased attentional selection requirements for the general task, and by the foreknowledge about the task sequence. When retrieval demands remained constant, frontal slow-waves elicited by retrieval-cues were more positive going for the specific task, indicating full implementation of a retrieval orientation that allows more efficient retrieval of perceptual details.

  9. Electrophoresis and spectrometric analyses of adaptation-related proteins in thermally stressed Chromobacterium violaceum.

    PubMed

    Cordeiro, I B; Castro, D P; Nogueira, P P O; Angelo, P C S; Nogueira, P A; Gonçalves, J F C; Pereira, A M R F; Garcia, J S; Souza, G H M F; Arruda, M A Z; Eberlin, M N; Astolfi-Filho, S; Andrade, E V; López-Lozano, J L

    2013-10-29

    Chromobacterium violaceum is a Gram-negative proteobacteria found in water and soil; it is widely distributed in tropical and subtropical regions, such as the Amazon rainforest. We examined protein expression changes that occur in C. violaceum at different growth temperatures using electrophoresis and mass spectrometry. The total number of spots detected was 1985; the number ranged from 99 to 380 in each assay. The proteins that were identified spectrometrically were categorized as chaperones, proteins expressed exclusively under heat stress, enzymes involved in the respiratory and fermentation cycles, ribosomal proteins, and proteins related to transport and secretion. Controlling inverted repeat of chaperone expression and inverted repeat DNA binding sequences, as well as regions recognized by sigma factor 32, elements involved in the genetic regulation of the bacterial stress response, were identified in the promoter regions of several of the genes coding proteins, involved in the C. violaceum stress response. We found that 30 °C is the optimal growth temperature for C. violaceum, whereas 25, 35, and 40 °C are stressful temperatures that trigger the expression of chaperones, superoxide dismutase, a probable small heat shock protein, a probable phasing, ferrichrome-iron receptor protein, elongation factor P, and an ornithine carbamoyltransferase catabolite. This information improves our comprehension of the mechanisms involved in stress adaptation by C. violaceum.

  10. Adaptive optics-assisted optical coherence tomography for imaging of patients with age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Sudo, Kenta; Cense, Barry

    2013-03-01

    We developed an optical coherence tomography (OCT) prototype with a sample arm that uses a 3.4 mm beam, which is considerably larger than the 1.2 to 1.5 mm beam that is used in commercialized OCT systems. The system is equipped with adaptive optics (AO), and to distinguish it from traditional AO-OCT systems with a larger 6 mm beam we have coined this concept AO-assisted OCT. Compared to commercialized OCT systems, the 3.4 mm aperture combined with AO improves light collection efficiency and imaging lateral resolution. In this paper, the performance of the AOa-OCT system was compared to a standard OCT system and demonstrated for imaging of age-related macular degeneration (AMD). Measurements were performed on the retinas of three human volunteers with healthy eyes and on one eye of a patient diagnosed with AMD. The AO-assisted OCT system imaged retinal structures of healthy human eyes and a patient eye affected by AMD with higher lateral resolution and a 9° by 9° field of view. This combination of a large isoplanatic patch and high lateral resolution can be expected to fill a gap between standard OCT with a 1.2 mm beam and conventional AO-OCT with a 6 mm beam and a 1.5° by 1.5° isoplanatic patch.

  11. Bony labyrinth morphometry indicates locomotor adaptations in the squirrel-related clade (Rodentia, Mammalia)

    PubMed Central

    Pfaff, Cathrin; Martin, Thomas; Ruf, Irina

    2015-01-01

    The semicircular canals (SCs) of the inner ear detect angular acceleration and are located in the bony labyrinth of the petrosal bone. Based on high-resolution computed tomography, we created a size-independent database of the bony labyrinth of 50 mammalian species especially rodents of the squirrel-related clade comprising taxa with fossorial, arboreal and gliding adaptations. Our sampling also includes gliding marsupials, actively flying bats, the arboreal tree shrew and subterranean species. The morphometric anatomy of the SCs was correlated to the locomotion mode. Even if the phylogenetic signal cannot entirely be excluded, the main significance for functional morphological studies has been found in the diameter of the SCs, whereas the radius of curvature is of minor interest. Additionally, we found clear differences in the bias angle of the canals between subterranean and gliding taxa, but also between sciurids and glirids. The sensitivity of the inner ear correlates with the locomotion mode, with a higher sensitivity of the SCs in fossorial species than in flying taxa. We conclude that the inner ear of flying and gliding mammals is less sensitive due to the large information flow into this sense organ during locomotion. PMID:26019162

  12. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    PubMed

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment.

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

    PubMed

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

    2015-08-01

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

  14. Reduced efficacy of natural selection on codon usage bias in selfing Arabidopsis and Capsella species.

    PubMed

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

    2011-01-01

    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 (N(e)) 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 N(e). 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.

  15. Factors That Shape Eukaryotic tRNAomes: Processing, Modification and Anticodon–Codon Use

    PubMed Central

    Maraia, Richard J.; Arimbasseri, Aneeshkumar G.

    2017-01-01

    Transfer RNAs (tRNAs) contain sequence diversity beyond their anticodons and the large variety of nucleotide modifications found in all kingdoms of life. Some modifications stabilize structure and fit in the ribosome whereas those to the anticodon loop modulate messenger RNA (mRNA) decoding activity more directly. The identities of tRNAs with some universal anticodon loop modifications vary among distant and parallel species, likely to accommodate fine tuning for their translation systems. This plasticity in positions 34 (wobble) and 37 is reflected in codon use bias. Here, we review convergent evidence that suggest that expansion of the eukaryotic tRNAome was supported by its dedicated RNA polymerase III transcription system and coupling to the precursor-tRNA chaperone, La protein. We also review aspects of eukaryotic tRNAome evolution involving G34/A34 anticodon-sparing, relation to A34 modification to inosine, biased codon use and regulatory information in the redundancy (synonymous) component of the genetic code. We then review interdependent anticodon loop modifications involving position 37 in eukaryotes. This includes the eukaryote-specific tRNA modification, 3-methylcytidine-32 (m3C32) and the responsible gene, TRM140 and homologs which were duplicated and subspecialized for isoacceptor-specific substrates and dependence on i6A37 or t6A37. The genetics of tRNA function is relevant to health directly and as disease modifiers. PMID:28282871

  16. Blastocystis Mitochondrial Genomes Appear to Show Multiple Independent Gains and Losses of Start and Stop Codons

    PubMed Central

    Jacob, Alison S.; Andersen, Lee O’Brien; Bitar, Paulina Pavinski; Richards, Vincent P.; Shah, Sarah; Stanhope, Michael J.; Stensvold, C. Rune; Clark, C. Graham

    2016-01-01

    Complete mitochondrion-related organelle (MRO) genomes of several subtypes (STs) of the unicellular stramenopile Blastocystis are presented. Complete conservation of gene content and synteny in gene order is observed across all MRO genomes, comprising 27 protein coding genes, 2 ribosomal RNA genes, and 16 transfer RNA (tRNA) genes. Despite the synteny, differences in the degree of overlap between genes were observed between subtypes and also between isolates within the same subtype. Other notable features include unusual base-pairing mismatches in the predicted secondary structures of some tRNAs. Intriguingly, the rps4 gene in some MRO genomes is missing a start codon and, based on phylogenetic relationships among STs, this loss has happened twice independently. One unidentified open reading frame (orf160) is present in all MRO genomes. However, with the exception of ST4 where the feature has been lost secondarily, orf160 contains variously one or two in-frame stop codons. The overall evidence suggests that both the orf160 and rps4 genes are functional in all STs, but how they are expressed remains unclear. PMID:27811175

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

    PubMed Central

    Detanico, Thiago; Phillips, Matthew; Wysocki, Lawrence J.

    2016-01-01

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

  18. Development of a Mediterranean diet score adapted to Japan and its relation to obesity risk

    PubMed Central

    Kanauchi, Masao; Kanauchi, Kimiko

    2016-01-01

    Background The Mediterranean diet (MD) is well known as a healthy diet that protects against several chronic diseases. However, there is no appropriate and easy index to assess adherence to the MD pattern in Japan. Objective The aim of this study was to develop a novel instrument to measure MD adherence adapted to a Japanese diet and to examine its association with overweight/obesity risk. Methods A cross-sectional nutritional survey provided the data for construction of a novel MD score. In total, 1,048 subjects who were employees and university students, aged 18–68 years (645 men and 403 women), completed a 58-item brief-type self-administered dietary history questionnaire. We constructed a Japanese-adapted MD score (jMD score) focusing on 13 components. Adherence to the jMD was categorized as low (score 0–4), moderate (5–7), or high (8–13). Results Men had higher jMD scores than women, and adherence to the jMD score increased with age. Only 11.6% of subjects showed high adherence to the jMD, whereas 29.6% showed low adherence. A higher jMD adherence was associated with a higher intake of favorable nutrients with the exception of salt. The jMD adherence was significantly associated with a reduced likelihood of having overweight/obesity for the highest category compared with lowest category (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.30–0.85, p-trend=0.017) after adjusting for age, sex, smoking, physical activity, alcohol intake, and hypertension. A two-point increment in jMD score was related to a reduced likelihood of having overweight/obesity with an odds ratio of 0.76 (95% CI 0.65–0.90, p=0.002). Conclusions Our novel jMD score confirmed reasonable associations with nutrient intakes, and higher MD adherence was associated with a lower prevalence of overweight/obesity. PMID:27806831

  19. Development of a Mediterranean diet score adapted to Japan and its relation to obesity risk.

    PubMed

    Kanauchi, Masao; Kanauchi, Kimiko

    2016-01-01

    The Mediterranean diet (MD) is well known as a healthy diet that protects against several chronic diseases. However, there is no appropriate and easy index to assess adherence to the MD pattern in Japan. The aim of this study was to develop a novel instrument to measure MD adherence adapted to a Japanese diet and to examine its association with overweight/obesity risk. A cross-sectional nutritional survey provided the data for construction of a novel MD score. In total, 1,048 subjects who were employees and university students, aged 18-68 years (645 men and 403 women), completed a 58-item brief-type self-administered dietary history questionnaire. We constructed a Japanese-adapted MD score (jMD score) focusing on 13 components. Adherence to the jMD was categorized as low (score 0-4), moderate (5-7), or high (8-13). Men had higher jMD scores than women, and adherence to the jMD score increased with age. Only 11.6% of subjects showed high adherence to the jMD, whereas 29.6% showed low adherence. A higher jMD adherence was associated with a higher intake of favorable nutrients with the exception of salt. The jMD adherence was significantly associated with a reduced likelihood of having overweight/obesity for the highest category compared with lowest category (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.30-0.85, p-trend=0.017) after adjusting for age, sex, smoking, physical activity, alcohol intake, and hypertension. A two-point increment in jMD score was related to a reduced likelihood of having overweight/obesity with an odds ratio of 0.76 (95% CI 0.65-0.90, p=0.002). Our novel jMD score confirmed reasonable associations with nutrient intakes, and higher MD adherence was associated with a lower prevalence of overweight/obesity.

  20. Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation.

    PubMed

    Hu, Minyi; Cheng, Jiqi; Bethel, Neville; Serra-Hsu, Frederick; Ferreri, Suzanne; Lin, Liangjun; Qin, Yi-Xian

    2014-09-01

    Interstitial bone fluid flow (IBFF) is suggested as a communication medium that bridges external physical signals and internal cellular activities in the bone, which thus regulates bone remodeling. Intramedullary pressure (ImP) is one main regulatory factor of IBFF and bone adaptation related mechanotransduction. Our group has recently observed that dynamic hydraulic stimulation (DHS), as an external oscillatory muscle coupling, was able to induce local ImP with minimal bone strain as well as to mitigate disuse bone loss. The current study aimed to evaluate the dose dependent relationship between DHS's amplitude, i.e., 15 and 30mmHg, and in vivo ImP induction, as well as this correlation on bone's phenotypic change. Simultaneous measurements of ImP and DHS cuff pressures were obtained from rats under DHS with various magnitudes and a constant frequency of 2Hz. ImP inductions and cuff pressures upon DHS loading showed a positively proportional response over the amplitude sweep. The relationship between ImP and DHS cuff pressure was evaluated and shown to be proportional, in which ImP was raised with increases of DHS cuff pressure amplitudes (R(2)=0.98). A 4-week in vivo experiment using a rat hindlimb suspension model demonstrated that the mitigation effect of DHS on disuse trabecular bone was highly dose dependent and related to DHS's amplitude, where a higher ImP led to a higher bone volume. This study suggested that sufficient physiological DHS is needed to generate ImP. Oscillatory DHS, potentially induces local fluid flow, has shown dose dependence in attenuation of disuse osteopenia.

  1. AFB1 hepatocarcinogenesis is via lipid peroxidation that inhibits DNA repair, sensitizes mutation susceptibility and induces aldehyde-DNA adducts at p53 mutational hotspot codon 249

    PubMed Central

    Hu, Yu; Mehta, Manju; Desai, Dhimant; Amin, Shantu; Zheng, Yi; Tang, Moon-Shong

    2017-01-01

    Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at –CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor. AFB1, Acet, and Cro can also inhibit DNA repair and enhance hepatocyte mutational sensitivity. We propose that AFB1-induced lipid peroxidation generated aldehydes contribute greatly to hepatocarcinogenesis and that sequence specificity of meth-OH-PdG formation and repair shape the codon 249 mutational hotspot. PMID:28212554

  2. Sliding of a 43S ribosomal complex from the recognized AUG codon triggered by a delay in eIF2-bound GTP hydrolysis

    PubMed Central

    Terenin, Ilya M.; Akulich, Kseniya A.; Andreev, Dmitry E.; Polyanskaya, Sofya A.; Shatsky, Ivan N.; Dmitriev, Sergey E.

    2016-01-01

    During eukaryotic translation initiation, 43S ribosomal complex scans mRNA leader unless an AUG codon in an appropriate context is found. Establishing the stable codon–anticodon base-pairing traps the ribosome on the initiator codon and triggers structural rearrangements, which lead to Pi release from the eIF2-bound GTP. It is generally accepted that AUG recognition by the scanning 43S complex sets the final point in the process of start codon selection, while latter stages do not contribute to this process. Here we use translation reconstitution approach and kinetic toe-printing assay to show that after the 48S complex is formed on an AUG codon, in case GTP hydrolysis is impaired, the ribosomal subunit is capable to resume scanning and slides downstream to the next AUG. In contrast to leaky scanning, this sliding is not limited to AUGs in poor nucleotide contexts and occurs after a relatively long pause at the recognized AUG. Thus, recognition of an AUG per se does not inevitably lead to this codon being selected for initiation of protein synthesis. Instead, it is eIF5-induced GTP hydrolysis and Pi release that irreversibly trap the 48S complex, and this complex is further stabilized by eIF5B and 60S joining. PMID:26717981

  3. fMRI-Adaptation Evidence of Overlapping Neural Representations for Objects Related in Function or Manipulation

    PubMed Central

    Yee, Eiling; Drucker, Daniel M.; Thompson-Schill, Sharon L.

    2010-01-01

    Sensorimotor-based theories of semantic memory contend that semantic information about an object is represented in the neural substrate invoked when we perceive or interact with it. We used fMRI adaptation to test this prediction, measuring brain activation as participants read pairs of words. Pairs shared function (flashlight–lantern), shape (marble–grape), both (pencil–pen), were unrelated (saucer–needle), or were identical (drill–drill). We observed adaptation for pairs with both function and shape similarity in left premotor cortex. Further, degree of function similarity was correlated with adaptation in three regions: two in the left temporal lobe (left medial temporal lobe, left middle temporal gyrus), which has been hypothesized to play a role in mutimodal integration, and one in left superior frontal gyrus. We also found that degree of manipulation (i.e., action) and function similarity were both correlated with adaptation in two regions: left premotor cortex and left intraparietal sulcus (involved in guiding actions). Additional considerations suggest that the adaptation in these two regions was driven by manipulation similarity alone; thus, these results imply that manipulation information about objects is encoded in brain regions involved in performing or guiding actions. Unexpectedly, these same two regions showed increased activation (rather than adaptation) for objects similar in shape. Overall, we found evidence (in the form of adaptation) that objects that share semantic features have overlapping representations. Further, the particular regions of overlap provide support for the existence of both sensorimotor and amodal/multimodal representations. PMID:20034582

  4. Adaptation status and related factors at 2 time points after surgery in patients with gastrointestinal tract cancer.

    PubMed

    Mizuno, Michiyo; Asano, Yoshihiro; Sumi, Tomomi; Inoue, Yumiko

    2011-01-01

    The diagnosis of cancer and subsequent surgery represent a life-threatening and stressful experience with several factors relating to the patient's process of adaptation. The purpose of this longitudinal study was to examine adaptation status and related factors in patients who have been diagnosed with and undergone surgery for gastrointestinal tract cancer. The survey was administered twice (2 weeks after discharge from the hospital and 6 months after surgery). Twenty-five patients responded to both questionnaires about quality of life (QOL), which was regarded as an index of adaptation status, and illness-related demands, the "why me?" question, sense of coherence (SOC), perceived social support, and disease data. On the second survey, scores about illness-related demands, the "why me?" question, SOC, and QOL, other than the QOL social relationships domain, improved, but scores about perceived social support decreased. A correlation between the "why me?" question and the SOC and the difference in the overall QOL by cancer site were found only on the second survey. Low demands of illness and high SOC predicted high QOL on both surveys. Except for social relationships, adaptation status 6 months after surgery improved compared with after discharge. The relationships between some variables took on a significant meaning at 6 months after surgery. Comparisons between 2 time points suggested that most cancer patients had dispositional resilience. Meanwhile, the findings related to social relationships and the relationships between some variables suggested the necessity for professional interventions targeting these factors.

  5. Codon-optimized Human Sodium Iodide Symporter (opt-hNIS) as a Sensitive Reporter and Efficient Therapeutic Gene

    PubMed Central

    Kim, Young-Hwa; Youn, Hyewon; Na, Juri; Hong, Kee-Jong; Kang, Keon Wook; Lee, Dong Soo; Chung, June-Key

    2015-01-01

    To generate a more efficient in vivo reporter and therapeutic gene, we optimized the coding sequence of the human sodium/iodide symporter (NIS) gene by replacing NIS DNA codons from wild type to new codons having the highest usage in human gene translation. The Codon Adaptation Index (CAI), representing the number of codons effective for human expression, was much improved (0.79 for hNIS, 0.97 for opt-hNIS). Both wild-type (hNIS) and optimized human NIS (opt-hNIS) were cloned into pcDNA3.1 and pMSCV vectors for transfection. Various cancer cell lines such as thyroid (TPC-1, FRO, B-CPAP), breast (MDA-MB-231), liver (Hep3B), cervical (HeLa), and glioma (U87MG) were transfected with pcDNA3.1/hNIS or pcDNA3.1/opt-hNIS. 125I uptake by opt-hNIS-expressing cells was 1.6 ~ 2.1 times higher than uptake by wild-type hNIS-expressing cells. Stable cell lines were also established by retroviral transduction using pMSCV/hNIS or pMSCV/opt-hNIS, revealing higher NIS protein levels and 125I uptake in opt-hNIS-expressing cells than in hNIS-expressing cells. Moreover, scintigraphic images from cell plates and mouse xenografts showed stronger signals from opt-hNIS-expressing cells than hNIS-expressing cells, and radioactivity uptake by opt-hNIS-expressing tumors was 2.3-fold greater than that by hNIS-expressing tumors. To test the efficacy of radioiodine therapy, mouse xenograft models were established with cancer cells expressing hNIS or opt-hNIS. 131I treatment reduced tumor sizes of hNIS- and opt-hNIS-expressing tumors to 0.57- and 0.27- fold, respectively, compared to their sizes before therapy, suggesting an improved therapeutic effect of opt-hNIS. In summary, this study shows that codon optimization strongly increases hNIS protein levels and radioiodine uptake, thus supporting opt-hNIS as a more sensitive reporter and efficient therapeutic gene. PMID:25553100

  6. Codon recognition during frameshift suppression in Saccharomyces cerevisiae.

    PubMed Central

    Gaber, R F; Culbertson, M R

    1984-01-01

    A genetic approach has been used to establish the molecular basis of 4-base codon recognition by frameshift suppressor tRNA containing an extra nucleotide in the anticodon. We have isolated all possible base substitution mutations at the position 4 (N) in the 3'-CCCN-5' anticodon of a Saccharomyces cerevisiae frameshift suppressor glycine tRNA encoded by the SUF16 gene. Base substitutions at +1 frameshift sites in the his4 gene have also been obtained such that all possible 4-base 5'-GGGN-3' codons have been identified. By testing for suppression in different strains that collectively represent all 16 possible combinations of position 4 nucleotides, we show that frameshift suppression does not require position 4 base pairing. Nonetheless, position 4 interactions influence the efficiency of suppression. Our results suggest a model in which 4-base translocation of mRNA on the ribosome is directed primarily by the number of nucleotides in the anticodon loop, whereas the resulting efficiency of suppression is dependent on the nature of position 4 nucleotides. Images PMID:6390183

  7. Age-related changes and sex differences in postural control adaptability in children during periodic floor oscillation with eyes closed.

    PubMed

    Fujiwara, Katsuo; Kiyota, Takeo; Mammadova, Aida; Yaguchi, Chie

    2011-01-01

    We investigated age-related changes and sex differences in adaptability of anticipatory postural control in children. Subjects comprised 449 children (4-12 years old) and 109 young adults (18-29 years old). Subjects stood with eyes closed on a force-platform fixed to a floor oscillator. We conducted five trials of 1-minute oscillation (0.5 Hz frequency, 2.5 cm amplitude) in the anteroposterior direction. Postural steadiness was quantified as the mean speed of the center of pressure in the anteroposterior direction (CoPy). In young adults, CoPy speed decreased rapidly until the third trial for both sexes. Adaptability was evaluated by changes in steadiness. The adaptability of children was categorized as "good," "moderate," and "poor," compared with a standard variation of the mean CoPy speed regression line between the first and fifth trials in young adults. Results were as follows: (1) anticipatory postural control adaptability starts to develop from age 6 in boys and 5 in girls, and greatly improves at age 7-8 in boys and 6 in girls; (2) the adaptability of children at age 11-12 (74% of boys and 63% of girls were categorized as "good") has not yet reached the same level as for young adults; (3) the adaptability at age 11-12 for girls is temporarily disturbed due to early puberty.

  8. Children's enduring PTSD symptoms are related to their family's adaptability and cohesion.

    PubMed

    Birmes, Philippe; Raynaud, Jean-Philippe; Daubisse, Laetitia; Brunet, Alain; Arbus, Christophe; Klein, Rémy; Cailhol, Lionel; Allenou, Charlotte; Hazane, Franck; Grandjean, Hélène; Schmitt, Laurent

    2009-08-01

    This study compared, 18-24 months after an industrial disaster, in two groups of children (those with clinically relevant PTSD symptoms versus those with low PTSD symptoms), the child's perception of family cohesion and adaptability, the child's experience of the explosion, and parental characteristics. Enmeshed family cohesion or rigid family adaptability were more frequently found in children with low PTSD symptoms. PTSD symptoms in the mother, living in a family of 3 or more children, and being female were significantly associated with PTSD symptoms in the children. The assessment of traumatized children should include assessment of family's adaptability and cohesion.

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

    PubMed

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

    2004-01-01

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

  10. The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects.

    PubMed

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

    2003-06-01

    Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigated the role of the PRNP polymorphism in 122 relatively young Italian DS patients. Allele frequencies of DS subjects did not differ from those in the general population. However, we found a significantly faster rate of decline in intellectual ability in the subgroup of DS patients carrying at least one V allele compared with the M/M DS subjects. An additive deleterious effect of apolipoprotein E epsilon 4 allele was detected after stratifying by APOE gene status. Our findings provide evidence that variability of the PRNP gene at codon 129 might contribute to accelerating the rate of earlier cognitive decline in DS subjects.

  11. [Cardiac enzymes related to high-altitude hypoxic adaptation in Tibetan chicken].

    PubMed

    Zhang, Hao; Wu, Chang-Xin; Chamba, Yangzom; Ling, Yao; Tang, Xiao-Hui

    2008-05-01

    The purpose of this experiment was to investigate the cardiac physiological characteristics for adaptation to high-altitude hypoxia in chickens. Tibetan, Dwarf Recessive White and Shouguang chickens were fed at low-and high-altitude, and measurements were made in heart weights, lactic acid (LA), lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH) at the age of 10 weeks. The results showed that Tibetan chickens at high-altitude had lower heart weight and LA content, and similar LDH activity, and higher SDH activity when compared to Dwarf Recessive White and Shouguang chickens. It was concluded that the cardiac mechanisms of high-altitude hypoxic adaptation in Tibetan chickens were increasing neither heart weight, nor level of anaerobic metabolism, but the higher SDH activity was significant to the adaptation. The SDH was a symbol enzyme for hypoxic adaptation in Tibetan chicken.

  12. Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

    2005-01-01

    Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

  13. Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

    2005-01-01

    Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

  14. Investigating the Impact of Formal Reflective Activities on Skill Adaptation in a Work-Related Instrumental Learning Setting

    ERIC Educational Resources Information Center

    Roessger, Kevin M.

    2013-01-01

    In work-related, instrumental learning contexts the role of reflective activities is unclear. Kolb's (1985) experiential learning theory and Mezirow's transformative learning theory (2000) predict skill-adaptation as a possible outcome. This prediction was experimentally explored by manipulating reflective activities and assessing participants'…

  15. Codon optimality is a major determinant of mRNA stability

    PubMed Central

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

    2015-01-01

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

  16. Are stop codons recognized by base triplets in the large ribosomal RNA subunit?

    PubMed

    Liang, Han; Landweber, Laura F; Fresco, Jacques R

    2005-10-01

    The precise mechanism of stop codon recognition in translation termination is still unclear. A previously published study by Ivanov and colleagues proposed a new model for stop codon recognition in which 3-nucleotide Ter-anticodons within the loops of hairpin helices 69 (domain IV) and 89 (domain V) in large ribosomal subunit (LSU) rRNA recognize stop codons to terminate protein translation in eubacteria and certain organelles. We evaluated this model by extensive bioinformatic analysis of stop codons and their putative corresponding Ter-anticodons across a much wider range of species, and found many cases for which it cannot explain the stop codon usage without requiring the involvement of one or more of the eight possible noncomplementary base pairs. Involvement of such base pairs may not be structurally or thermodynamically damaging to the model. However, if, according to the model, Ter-anticodon interaction with stop codons occurs within the ribosomal A-site, the structural stringency which that site imposes on sense codon.tRNA anticodon interaction should also extend to stop codon.Ter-anticodon interactions. Moreover, with Ter-tRNA in place of an aminoacyl-tRNA, for each of the various Ter-anticodons there is a sense codon that can interact with it preferentially by complementary and wobble base-pairing. Both these considerations considerably weaken the arguments put forth previously.

  17. Codon-specific and general inhibition of protein synthesis by the tRNA-sequestering minigenes.

    PubMed

    Delgado-Olivares, Luis; Zamora-Romo, Efraín; Guarneros, Gabriel; Hernandez-Sanchez, Javier

    2006-07-01

    The expression of minigenes in bacteria inhibits protein synthesis and cell growth. Presumably, the translating ribosomes, harboring the peptides as peptidyl-tRNAs, pause at the last sense codon of the minigene directed mRNAs. Eventually, the peptidyl-tRNAs drop off and, under limiting activity of peptidyl-tRNA hydrolase, accumulate in the cells reducing the concentration of specific aminoacylable tRNA. Therefore, the extent of inhibition is associated with the rate of starvation for a specific tRNA. Here, we used minigenes harboring various last sense codons that sequester specific tRNAs with different efficiency, to inhibit the translation of reporter genes containing, or not, these codons. A prompt inhibition of the protein synthesis directed by genes containing the codons starved for their cognate tRNA (hungry codons) was observed. However, a non-specific in vitro inhibition of protein synthesis, irrespective of the codon composition of the gene, was also evident. The degree of inhibition correlated directly with the number of hungry codons in the gene. Furthermore, a tRNA(Arg4)-sequestering minigene promoted the production of an incomplete beta-galactosidase polypeptide interrupted, during bacterial polypeptide chain elongation at sites where AGA codons were inserted in the lacZ gene suggesting ribosome pausing at the hungry codons.

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

    NASA Astrophysics Data System (ADS)

    Mitarai, Namiko; Pedersen, Steen

    2013-10-01

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

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

    SciTech Connect

    Petraroli, R.; Pocchiari, M.

    1996-04-01

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

  20. An Attentional Adaptation Account of Spatial Negative Priming: Evidence from Event-Related Potentials

    PubMed Central

    Liu, Xiaonan L.; Walsh, Matthew M.; Reder, Lynne M.

    2014-01-01

    Negative priming (NP) refers to a slower response to a target stimulus if it has been previously ignored. To examine theoretical accounts of spatial NP, we recorded behavioral measures and event-related potentials (ERPs) in a target localization task. A target and distractor briefly appeared, and the participant pressed a key corresponding to the target's location. The probability of the distractor appearing in each of four locations varied, while the target appeared with equal probability in each location. We found that reaction times (RTs) were fastest when the prime distractor appeared in its most probable (frequent) location and when the prime target appeared in the location that never contained a distractor. Moreover, NP effects varied as a function of location: they were smallest when targets followed distractors in the frequent distractor location – a finding not predicted by episodic retrieval or suppression accounts of NP. ERP results showed that the P2, an ERP component associated with attentional orientation, was smaller in prime displays when the distractor appeared in its frequent location. Moreover there were no differences between negative prime and control trials in the N2, which is associated with suppression processes, nor in the P3, which is associated with episodic retrieval processes. These results indicate that the spatial NP effect is caused by both short- and long-term adaptation in preferences based on the history of inspecting unsuccessful locations. This paper is dedicated to the memory of Edward E. Smith and we indicate how this study is inspired by his research career. PMID:24464637

  1. Adaptation and Validation of the Voice-Related Quality of Life Measure Into Polish.

    PubMed

    Sielska-Badurek, Ewelina; Rzepakowska, Anna; Sobol, Maria; Osuch-Wójcikiewicz, Ewa; Niemczyk, Kazimierz

    2016-11-01

    The purpose of the study was to translate and adapt the original V-RQOL (Voice-Related Quality of Life) instrument into Polish and to evaluate the psychometric properties of the Polish version of the V-RQOL Measure such as internal consistency, reliability, and construct validity in different groups of dysphonic patients. A total of 214 patients with voice disorders were assessed using the V-RQOL Measure, the Voice Handicap Index, and the World Health Organization Quality of Life, short version. The Polish version of the V-RQOL Measure showed strong internal consistency with the Cronbach alpha coefficient: 0.92 for the total score, 0.90 for the social-emotional domain, and 0.86 for the physical functioning domain, and a good test-retest reliability (r-Spearman correlation coefficient: r = 0.8852 for the total score of the V-RQOL Measure). Construct validity was demonstrated with a strong correlation to the Voice Handicap Index (r = -0.843, P = 0.000*) and a weak positive, statistically significant correlation between the V-RQOL-physical functioning domain, V-RQOL-social-emotional domain, and the Q1, Q2, and Domain 1-Domain 4 of the World Health Organization Quality of Life, short version (0.2 < r < 0.4). The Polish version of the V-RQOL Measure is a valid and reliable instrument to evaluate the patient's perception of his or her own voice disorders and the impact it can have on the patient's life. The V-RQOL Measure is easy to perform in clinical practice. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  2. Age-Related, Sport-Specific Adaptions of the Shoulder Girdle in Elite Adolescent Tennis Players

    PubMed Central

    Cools, Ann M.; Palmans, Tanneke; Johansson, Fredrik R.

    2014-01-01

    Context: Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. Objective: To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (<14, 14–16, and >16 years). Design: Cross-sectional study. Setting: Tennis training sports facilities. Patients or Other Participants: Fifty-nine adolescent Swedish elite tennis players (ages 10–20 years) selected based on their national ranking. Main Outcome Measure(s): We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Results: Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight–normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Conclusions: Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence. PMID:25098662

  3. An attentional-adaptation account of spatial negative priming: evidence from event-related potentials.

    PubMed

    Liu, Xiaonan L; Walsh, Matthew M; Reder, Lynne M

    2014-03-01

    Negative priming (NP) refers to a slower response to a target stimulus if it has been previously ignored. To examine theoretical accounts of spatial NP, we recorded behavioral measures and event-related potentials (ERPs) in a target localization task. A target and distractor briefly appeared, and the participant pressed a key corresponding to the target's location. The probability of the distractor appearing in each of four locations varied, whereas the target appeared with equal probabilities in all locations. We found that response times (RTs) were fastest when the prime distractor appeared in its most probable (frequent) location and when the prime target appeared in the location that never contained a distractor. Moreover, NP effects varied as a function of location: They were smallest when targets followed distractors in the frequent distractor location-a finding not predicted by episodic-retrieval or suppression accounts of NP. The ERP results showed that the P2, an ERP component associated with attentional orientation, was smaller in prime displays when the distractor appeared in its frequent location. Moreover, no differences were apparent between negative-prime and control trials in the N2, which is associated with suppression processes, nor in the P3, which is associated with episodic retrieval processes. These results indicate that the spatial NP effect is caused by both short- and long-term adaptation in preferences based on the history of inspecting unsuccessful locations. This article is dedicated to the memory of Edward E. Smith, and we indicate how this study was inspired by his research career.

  4. Age-related, sport-specific adaptions of the shoulder girdle in elite adolescent tennis players.

    PubMed

    Cools, Ann M; Palmans, Tanneke; Johansson, Fredrik R

    2014-01-01

    Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (<14, 14-16, and >16 years). Cross-sectional study. Tennis training sports facilities. Fifty-nine adolescent Swedish elite tennis players (ages 10-20 years) selected based on their national ranking. We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight-normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence.

  5. Role of Calcitonin Gene-Related Peptide in Functional Adaptation of the Skeleton

    PubMed Central

    Sample, Susannah J.; Heaton, Caitlin M.; Behan, Mary; Bleedorn, Jason A.; Racette, Molly A.; Hao, Zhengling; Muir, Peter

    2014-01-01

    Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPβ. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPβ knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPβ knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation. PMID:25536054

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

    SciTech Connect

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

    1993-10-01

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

  7. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2014-10-01

    an adaptation response to an anabolic mechanical stimulus, but that once this adaptation response has been activated, bone formation occurs to a...but  capsaicin‐ treated mice exhibited the  greatest  anabolic   response. More distal sites  also  exhibited  a  small  but  significant response...EF, Einhorn TA. Anabolic agents and bone quality. Clin Orthop Relat Res 2011;469:2215-24. 5. Ceballos D, Cuadras J, Verdu E, Navarro X. Morphome

  8. fMRI-adaptation evidence of overlapping neural representations for objects related in function or manipulation.

    PubMed

    Yee, Eiling; Drucker, Daniel M; Thompson-Schill, Sharon L

    2010-04-01

    Sensorimotor-based theories of semantic memory contend that semantic information about an object is represented in the neural substrate invoked when we perceive or interact with it. We used fMRI adaptation to test this prediction, measuring brain activation as participants read pairs of words. Pairs shared function (flashlight-lantern), shape (marble-grape), both (pencil-pen), were unrelated (saucer-needle), or were identical (drill-drill). We observed adaptation for pairs with both function and shape similarity in left premotor cortex. Further, degree of function similarity was correlated with adaptation in three regions: two in the left temporal lobe (left medial temporal lobe, left middle temporal gyrus), which has been hypothesized to play a role in mutimodal integration, and one in left superior frontal gyrus. We also found that degree of manipulation (i.e., action) and function similarity were both correlated with adaptation in two regions: left premotor cortex and left intraparietal sulcus (involved in guiding actions). Additional considerations suggest that the adaptation in these two regions was driven by manipulation similarity alone; thus, these results imply that manipulation information about objects is encoded in brain regions involved in performing or guiding actions. Unexpectedly, these same two regions showed increased activation (rather than adaptation) for objects similar in shape. Overall, we found evidence (in the form of adaptation) that objects that share semantic features have overlapping representations. Further, the particular regions of overlap provide support for the existence of both sensorimotor and amodal/multimodal representations. Copyright 2009 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2014-01-01

    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

  10. Why time matters: codon evolution and the temporal dynamics of dN/dS.

    PubMed

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

    2014-01-01

    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.

  11. Waterloo Vision and Mobility Study: gait adaptations to altered surfaces in individuals with age-related maculopathy.

    PubMed

    Spaulding, S J; Patla, A E; Elliott, D B; Flanagan, J; Rietdyk, S; Brown, S

    1994-12-01

    Walking is an extremely complex task that can become seriously challenged if one of the sensory systems which provides input to the motor system is compromised. The present study evaluated gait adaptations to altered surface characteristics and high and low ambient light conditions by subjects with age-related maculopathy (ARM). Twenty subjects with ARM and 20 control subjects walked along a 6 m path, along which they met 1 of 3 altered surfaces (compliant, uneven, or shiny). Kinematic data and ground reaction forces information were analyzed to discern gait adaptation strategies used by the ARM group. Ten trials on each surface were collected under both high and low ambient light levels. The ARM subjects were found to be generally more cautious when walking on the altered surfaces. For example, they walked more slowly, with a longer swing time. However, gait adaptations in the ARM group were not merely scaled versions of normal gait but were adjustments to adapt to environmental changes. Gait was modified to avoid tripping over a surface edge, to prevent slipping at heel contact, and to balance during stance. These adaptations enabled subjects to maintain safe mobility when walking in a challenging environment.

  12. Age-related decline in thermal adaptation capacities: an evoked potentials study.

    PubMed

    Kemp, Jennifer; Després, Olivier; Pebayle, Thierry; Dufour, André

    2014-06-01

    Aging is associated with changes in thermosensitivity and decreases in the functionality of the autonomic thermoregulation. The underlying mechanisms are, however, not fully understood. Elderly subjects may undergo functional changes in the integration process of the thermal sensory system, especially in their thermal adaptation capacities. To verify this hypothesis, we compared thermal evoked responses in younger and older subjects exposed to thermoneutral (27 °C) and warm (30 °C) environments. In the warm environment, the amplitudes of thermal evoked potentials (EPs) were significantly lower in older than in younger subjects, whereas in the thermoneutral environment, the EP amplitudes were similar in both groups. These findings suggest that thermal adaptation capacities are reduced in elderly individuals, due to a dysfunction of C-fibers with aging, particularly expressed by lowered adaptation capacities to temperature variations. Copyright © 2014 Society for Psychophysiological Research.

  13. Extended Lyapunov stability criterion using a nonlinear algebraic relation with application to adaptive control

    NASA Technical Reports Server (NTRS)

    Colburn, B. K.; Boland, J. S., III

    1976-01-01

    A new nonlinear stability criterion is developed by use of a class of Lyapunov functionals for model-reference adaptive systems (MRAS). Results are compared with traditional results, and a comparative design technique is used to illustrate its function in improving the transient response of an MRAS controller. For a particular system structure and class of input signals, the new stability criterion is shown to include traditional sufficiency stability conditions as a special case. An example is cited to illustrate the use of the nonlinear criterion and its definite advantages in helping improve the adaptive error transient response of a system. Analysis of results is effected by use of a linearization technique on the resulting adaptive equations.

  14. The preliminary study of p53 codon 72 polymorphism and risk of cervical carcinoma in Gabonese women.

    PubMed

    Assoumou, Samira Zoa; Boumba, Anicet Luc M; Ndjoyi-Mbiguino, Angelique; Khattabi, Abdelkrim; Ennaji, Moulay Mustapha

    2015-01-01

    Cervical cancer is the leading cause of cancer-related death in Africa and the first most common cancer in Gabonese women due to infection of high-risk human papillomavirus (HPV). However, other cofactors such as genetic factors also come into play. A common polymorphism of the p53 codon 72 in exon 4 with two alleles encoding arginine or proline is known at this locus. The homozygous arginine form of this polymorphism has been associated with the development of cervical cancer as an increased genetic risk factor. However, the results are still controversial. This study aims to investigate whether the genotype distribution of p53 codon 72 may be a risk factor for cervical cancer among Gabonese women. Samples from 102 Gabonese women, 31 diagnosed with cervical cancer and 71 healthy controls, were used. HPV detection was done by nested PCR with MY09/11 and GP5+/6+ primers followed by sequencing for HPV genotyping. p53 codon 72 polymorphism determination was performed by allele-specific PCR assay. Viral DNA was detected in 87.1 % of cases and in 54.93 % of control. HPV 16 was the most predominant in cancer and controls cases. The distribution of Arg/Arg, Arg/Pro and Pro/Pro genotypes was 35.5, 51.6 and 12.9 % in the cervical cancer group and 22.5, 62 and 15.5 % in the control group. No significant association was found between polymorphism of p53 itself as well as in combination with HPV16/18 infection and risk of development of cervical cancer among Gabonese women. Thus, the polymorphism of p53 codon 72 in exon 4 does not seem to play a role in the development of cervical cancer among Gabonese women.

  15. [Analysis on the preference of synonymous codon in VP1 nucleotide sequence of the EV71 based on RSCU method].

    PubMed

    Qi, Bin; Zhao, Jing-Jing; Gao, Lei; Zhu, Ping

    2009-11-01

    Based on RSCU method and by analyzing the preference of codon usage in VP1 nucleotide sequences of EV71 isolated in Chinese mainland and Taiwan region from 1998 to 2008, it is clear that there is an obvious time discrimination in RSCU calculated from EV71 VP1 strain between two different regions of China and it is more obvious in Taiwan region, therefore, according to the diversity of RSCU, the years can be divided into 2 intervals in Chinese mainland and 4 intervals in Taiwan region, especially, the number of intervals in one region have a positive co-relation with the activity of variation of the EV71 in the same region. The change of the preference of codon usage in VP1 nucleotide sequences of EV71 can significantly embody the Variation of the EV71, so we can make use of the analysis on preference of codon usage in VP1 nucleotide sequences of EV71 to predict the possible variation trend of the EV71.

  16. Codon Optimization to Enhance Expression Yields Insights into Chloroplast Translation1[OPEN

    PubMed Central

    Chan, Hui-Ting; Williams-Carrier, Rosalind; Barkan, Alice

    2016-01-01

    Codon optimization based on psbA genes from 133 plant species eliminated 105 (human clotting factor VIII heavy chain [FVIII HC]) and 59 (polio VIRAL CAPSID PROTEIN1 [VP1]) rare codons; replacement with only the most highly preferred codons decreased transgene expression (77- to 111-fold) when compared with the codon usage hierarchy of the psbA genes. Targeted proteomic quantification by parallel reaction monitoring analysis showed 4.9- to 7.1-fold or 22.5- to 28.1-fold increase in FVIII or VP1 codon-optimized genes when normalized with stable isotope-labeled standard peptides (or housekeeping protein peptides), but quantitation using western blots showed 6.3- to 8-fold or 91- to 125-fold increase of transgene expression from the same batch of materials, due to limitations in quantitative protein transfer, denaturation, solubility, or stability. Parallel reaction monitoring, to our knowledge validated here for the first time for in planta quantitation of biopharmaceuticals, is especially useful for insoluble or multimeric proteins required for oral drug delivery. Northern blots confirmed that the increase of codon-optimized protein synthesis is at the translational level rather than any impact on transcript abundance. Ribosome footprints did not increase proportionately with VP1 translation or even decreased after FVIII codon optimization but is useful in diagnosing additional rate-limiting steps. A major ribosome pause at CTC leucine codons in the native gene of FVIII HC was eliminated upon codon optimization. Ribosome stalls observed at clusters of serine codons in the codon