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Sample records for relative codon adaptation

  1. Codon Adaptation of Plastid Genes.

    PubMed

    Suzuki, Haruo; Morton, Brian R

    2016-01-01

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

  2. 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

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

    PubMed Central

    Prabhakaran, Ramanandan; Chithambaram, Shivapriya

    2015-01-01

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

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

    PubMed

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

    2016-05-01

    Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress. PMID:26874685

  5. Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation.

    PubMed

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

    2016-09-15

    Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD. PMID:27275533

  6. 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

  7. JCat: a novel tool to adapt codon usage of a target gene to its potential expression host.

    PubMed

    Grote, Andreas; Hiller, Karsten; Scheer, Maurice; Münch, Richard; Nörtemann, Bernd; Hempel, Dietmar C; Jahn, Dieter

    2005-07-01

    A novel method for the adaptation of target gene codon usage to most sequenced prokaryotes and selected eukaryotic gene expression hosts was developed to improve heterologous protein production. In contrast to existing tools, JCat (Java Codon Adaptation Tool) does not require the manual definition of highly expressed genes and is, therefore, a very rapid and easy method. Further options of JCat for codon adaptation include the avoidance of unwanted cleavage sites for restriction enzymes and Rho-independent transcription terminators. The output of JCat is both graphically and as Codon Adaptation Index (CAI) values given for the pasted sequence and the newly adapted sequence. Additionally, a list of genes in FASTA-format can be uploaded to calculate CAI values. In one example, all genes of the genome of Caenorhabditis elegans were adapted to Escherichia coli codon usage and further optimized to avoid commonly used restriction sites. In a second example, the Pseudomonas aeruginosa exbD gene codon usage was adapted to E.coli codon usage with parallel avoidance of the same restriction sites. For both, the degree of introduced changes was documented and evaluated. JCat is integrated into the PRODORIC database that hosts all required information on the various organisms to fulfill the requested calculations. JCat is freely accessible at http://www.prodoric.de/JCat. PMID:15980527

  8. 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. PMID:16171828

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

    PubMed Central

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

    2011-01-01

    Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation. PMID:21966531

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

    PubMed

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

    2016-06-01

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

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

    PubMed

    Ma, Bin-Guang; Chen, Ling-Ling

    2005-10-01

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

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

    PubMed Central

    Puigbò, Pere; Bravo, Ignacio G; Garcia-Vallvé, Santiago

    2008-01-01

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

  13. Hepatitis A Virus Adaptation to Cellular Shutoff Is Driven by Dynamic Adjustments of Codon Usage and Results in the Selection of Populations with Altered Capsids

    PubMed Central

    Costafreda, M. Isabel; Pérez-Rodriguez, Francisco J.; D'Andrea, Lucía; Guix, Susana; Ribes, Enric; Bosch, Albert

    2014-01-01

    ABSTRACT Hepatitis A virus (HAV) has a highly biased and deoptimized codon usage compared to the host cell and fails to inhibit host protein synthesis. It has been proposed that an optimal combination of abundant and rare codons controls the translation speed required for the correct capsid folding. The artificial shutoff host protein synthesis results in the selection of variants containing mutations in the HAV capsid coding region critical for folding, stability, and function. Here, we show that these capsid mutations resulted in changes in their antigenicity; in a reduced stability to high temperature, low pH, and biliary salts; and in an increased efficacy of cell entry. In conclusion, the adaptation to cellular shutoff resulted in the selection of large-plaque-producing virus populations. IMPORTANCE HAV has a naturally deoptimized codon usage with respect to that of its cell host and is unable to shut down the cellular translation. This fact contributes to the low replication rate of the virus, in addition to other factors such as the highly inefficient internal ribosome entry site (IRES), and explains the outstanding physical stability of this pathogen in the environment mediated by a folding-dependent highly cohesive capsid. Adaptation to artificially induced cellular transcription shutoff resulted in a redeoptimization of its capsid codon usage, instead of an optimization. These genomic changes are related to an overall change of capsid folding, which in turn induces changes in the cell entry process. Remarkably, the adaptation to cellular shutoff allowed the virus to significantly increase its RNA uncoating efficiency, resulting in the selection of large-plaque-producing populations. However, these populations produced much-debilitated virions. PMID:24554668

  14. 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

  15. 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

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-08-01

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

  2. 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

  3. Over expression of a synthetic gene encoding interferon lambda using relative synonymous codon usage bias in Escherichia coli.

    PubMed

    Akhtar, Hashaam; Akhtar, Samar; Jan, Syed Umer; Khan, Azka; Zaidi, Najam us Sahar Sadaf; Qadri, Ishtiaq

    2013-11-01

    Interferon Lambda (IFN-λ) is a type III interferon which belongs to a novel family of cytokines and possesses antiviral and antitumor properties. It is unique in its own class of cytokines; because of the specificity towards its heterodimer receptors and its structural similarities with cytokines of other classes. This renders IFN-λ a better choice for the treatment against many diseases including viral hepatitis and human coronavirus (HCoV-EMC). The present study describes a computational approach known as relative synonymous codon usage (RSCU); used to enhance the expression of IFN-λ protein in a eukaryotic expression system. Manually designed and commercially synthesized IFN-λ gene was cloned into pET-22b expression plasmid under the control of inducible T7-lac promoter. Maximum levels of IFN-λ expression was observed with 0.4 mM IPTG in transformed E. coli incubated for 4 hours in LB medium. Higher concentrations of IPTG had no or negative effect on the expression of IFN-λ. This synthetically over expressed IFN-λ can be tested as a targeted treatment option for viral hepatitis after purification. PMID:24191324

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

    PubMed

    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

  5. Characterization of codon usage pattern and influencing factors in Japanese encephalitis virus.

    PubMed

    Singh, Niraj K; Tyagi, Anuj; Kaur, Rajinder; Verma, Ramneek; Gupta, Praveen K

    2016-08-01

    Recently, several outbreaks of Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV), have been reported and it has become cause of concern across the world. In this study, detailed analysis of JEV codon usage pattern was performed. The relative synonymous codon usage (RSCU) values along with mean effective number of codons (ENC) value of 55.30 indicated the presence of low codon usages bias in JEV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations of A3s, U3s, G3s, C3s, GC3s, ENC values, with overall nucleotide contents (A%, U%, G%, C%, and GC%). The correlation analysis of A3s, U3s, G3s, C3s, GC3s, with axis values of correspondence analysis (CoA) further confirmed the role of mutational pressure. However, the correlation analysis of Gravy values and Aroma values with A3s, U3s, G3s, C3s, and GC3s, indicated the presence of natural selection on codon usage bias in addition to mutational pressure. The natural selection was further confirmed by codon adaptation index (CAI) analysis. Additionally, relative dinucleotide frequencies, geographical distribution, and evolutionary processes also influenced the codon usage pattern to some extent. PMID:27189042

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

    PubMed Central

    Bulmer, M

    1990-01-01

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

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

    PubMed

    Padhi, Abinash; Verghese, Bindhu

    2008-03-01

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

  8. 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

  9. Di-codon Usage for Gene Classification

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2016-01-01

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

  11. 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

  12. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-01-22

    Ebola virus (EBOV) is a member of the family Filoviridae and its genome consists of a 19-kb, single-stranded, negative sense RNA. EBOV is subdivided into five distinct species with different pathogenicities, being Zaire ebolavirus (ZEBOV) the most lethal species. The interplay of codon usage among viruses and their hosts is expected to affect overall viral survival, fitness, evasion from host's immune system and evolution. In the present study, we performed comprehensive analyses of codon usage and composition of ZEBOV. Effective number of codons (ENC) indicates that the overall codon usage among ZEBOV strains is slightly biased. Different codon preferences in ZEBOV genes in relation to codon usage of human genes were found. Highly preferred codons are all A-ending triplets, which strongly suggests that mutational bias is a main force shaping codon usage in ZEBOV. Dinucleotide composition also plays a role in the overall pattern of ZEBOV codon usage. ZEBOV does not seem to use the most abundant tRNAs present in the human cells for most of their preferred codons. PMID:25445348

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

    PubMed

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

    2016-01-01

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

  16. 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

  17. Glutathione-S-Transferase M1 and codon 72 p53 polymorphisms in a northwestern Mediterranean population and their relation to lung cancer susceptibility.

    PubMed

    To-Figueras, J; Gene, M; Gomez-Catalan, J; Galan, C; Firvida, J; Fuentes, M; Rodamilans, M; Huguet, E; Estape, J; Corbella, J

    1996-05-01

    Several polymorphic genes have been reported to be possibly involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in human populations, and the null genotype has been reported to be a risk factor for developing lung carcinoma. A germline polymorphism of p53 with a single-base change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC) by proline (PRO; CCC) has also been reported to be associated with cancer susceptibility in a Japanese population. Both polymorphisms were genotyped by PCR in a northwestern Mediterranean healthy population (n = 147) and in a group of lung cancer patients (n = 139). The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51]. The histological subtypes most clearly modified were small cell carcinoma (OR, 1.89; CI, 0.97-3.65) and adenocarcinoma (OR, 1.93; CI, 0.90-4.14). The null GSTM1 genotype was more frequent among those cancer patients who were medium/ light smokers (< or = 50 pack-years) and in those who showed an onset of the disease at a more advanced age. The study of the p53 polymorphism in the healthy population showed allele frequencies of 0.79 (Arg) and 0.21 (Pro). The frequencies found in the lung cancer patients were statistically similar. Both polymorphisms were studied together, and the relative risk of the combination null GSTM1 and Pro/Pro or Arg/Pro genotypes was calculated taking the combination of GTSM1 + together with Arq/Arg as a baseline. The OR found (1.97; CI, 1.03-3.73) suggests that the Pro allele of the p53 germline polymorphism may slightly increase the risk fo the GSTM1 null genotype among smokers. PMID:9162298

  18. 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.

  19. 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.

  20. Effects of nucleotide usage on the synonymous codon usage patterns of biofilm-associated genes in Haemophilus parasuis.

    PubMed

    Wang, L Y; Ma, L N; Liu, Y S

    2016-01-01

    To provide a new perspective on the evolutionary characteristics shaping the genetic diversity of Haemophilus parasuis biofilms, the relative synonymous codon usage values, codon usage bias values, effective number of codons (ENC) values, codon adaptation index (CAI) values, and the base components were calculated. Our objective was to implement a comparative analysis to evaluate the dynamic evolution of biofilm-associated genes in H. parasuis. The analysis of genetic diversity provides evidence that some biofilm-associated genes have similar genetic features. However, other genes show some variations in genetic direction. Furthermore, preferential selection of the synonymous codons and amino acids is apparent in biofilm-associated genes. Additionally, the ENC and CAI data from this study all strongly suggested that biofilm-associated genes may depend on deoptimization to adapt to environmental changes, and the mutation effect of biofilm-associated genes in H. parasuis plays an important role in shaping the genetic features. Our results reveal that the mutations of biofilm-associated genes form a set of sophisticated strategies for combating the environmental changes arising from the host cell in the evolution of H. parasuis. PMID:27323145

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

    PubMed Central

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

    2015-01-01

    Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino acid, are used differently across the variety of living organisms. The biological meaning of this phenomenon, known as codon usage bias, is still controversial. In order to shed light on this point, we propose a new codon bias index, CompAI, that is based on the competition between cognate and near-cognate tRNAs during translation, without being tuned to the usage bias of highly expressed genes. We perform a genome-wide evaluation of codon bias for E.coli, comparing CompAI with other widely used indices: tAI, CAI, and Nc. We show that CompAI and tAI capture similar information by being positively correlated with gene conservation, measured by the Evolutionary Retention Index (ERI), and essentiality, whereas, CAI and Nc appear to be less sensitive to evolutionary-functional parameters. Notably, the rate of variation of tAI and CompAI with ERI allows to obtain sets of genes that consistently belong to specific clusters of orthologous genes (COGs). We also investigate the correlation of codon bias at the genomic level with the network features of protein-protein interactions in E.coli. We find that the most densely connected communities of the network share a similar level of codon bias (as measured by CompAI and tAI). Conversely, a small difference in codon bias between two genes is, statistically, a prerequisite for the corresponding proteins to interact. Importantly, among all codon bias indices, CompAI turns out to have the most coherent distribution over the communities of the interactome, pointing to the significance of competition among cognate and near-cognate tRNAs for explaining codon usage adaptation. Notably, CompAI may potentially correlate with translation speed measurements, by accounting for the specific delay induced by wobble-pairing between codons and anticodons. PMID:26566157

  2. 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

  3. Stop codons in bacteria are not selectively equivalent

    PubMed Central

    2012-01-01

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

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

    PubMed

    Morla, Sudhir; Makhija, Aditi; Kumar, Sachin

    2016-06-10

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

  5. 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

  6. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species.

    PubMed

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-09-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3 This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

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

    PubMed

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

    2004-07-01

    A codon-profile strategy was used to predict gene expression levels in Streptococcus pneumoniae. Predicted highly expressed (PHE) genes included those encoding glycolytic and fermentative enzymes, sugar-conversion systems and carbohydrate-transporters. Additionally, some genes required for infection that are involved in oxidative metabolism and hydrogen peroxide production were PHE. Low expression values were predicted for genes encoding specific regulatory proteins like two-component systems and competence genes. Correspondence analysis localized 484 ORFs which shared a distinctive codon profile in the right horn. These genes had a mean G+C content (33.4 %) that was lower than the bulk of the genome coding sequences (39.7 %), suggesting that many of them were acquired by horizontal transfer. Half of these genes (242) were pseudogenes, ORFs shorter than 80 codons or without assigned function. The remaining genes included several virulence factors, such as capsular genes, iga, lytB, nanB, pspA, choline-binding proteins, and functions related to DNA acquisition, such as restriction-modification systems and comDE. In order to compare predicted translation rate with the relative amounts of mRNA for each gene, the codon adaptation index (CAI) values were compared with microarray fluorescence intensity values following hybridization of labelled RNA from laboratory-grown cultures. High mRNA amounts were observed in 32.5 % of PHE genes and in 64 % of the 25 genes with the highest CAI values. However, high relative amounts of RNA were also detected in 10.4 % of non-PHE genes, such as those encoding fatty acid metabolism enzymes and proteases, suggesting that their expression might also be regulated at the level of transcription or mRNA stability under the conditions tested. The effects of codon bias and mRNA amount on different gene groups in S. pneumoniae are discussed. PMID:15256573

  8. Coevolution between Stop Codon Usage and Release Factors in Bacterial Species

    PubMed Central

    Wei, Yulong; Wang, Juan; Xia, Xuhua

    2016-01-01

    Three stop codons in bacteria represent different translation termination signals, and their usage is expected to depend on their differences in translation termination efficiency, mutation bias, and relative abundance of release factors (RF1 decoding UAA and UAG, and RF2 decoding UAA and UGA). In 14 bacterial species (covering Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria and Spirochetes) with cellular RF1 and RF2 quantified, UAA is consistently over-represented in highly expressed genes (HEGs) relative to lowly expressed genes (LEGs), whereas UGA usage is the opposite even in species where RF2 is far more abundant than RF1. UGA usage relative to UAG increases significantly with PRF2 [=RF2/(RF1 + RF2)] as expected from adaptation between stop codons and their decoders. PRF2 is > 0.5 over a wide range of AT content (measured by PAT3 as the proportion of AT at third codon sites), but decreases rapidly toward zero at the high range of PAT3. This explains why bacterial lineages with high PAT3 often have UGA reassigned because of low RF2. There is no indication that UAG is a minor stop codon in bacteria as claimed in a recent publication. The claim is invalid because of the failure to apply the two key criteria in identifying a minor codon: (1) it is least preferred by HEGs (or most preferred by LEGs) and (2) it corresponds to the least abundant decoder. Our results suggest a more plausible explanation for why UAA usage increases, and UGA usage decreases, with PAT3, but UAG usage remains low over the entire PAT3 range. PMID:27297468

  9. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Rothberg, P G; Wimmer, E

    1981-01-01

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

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

    PubMed

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

    2015-04-01

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

  13. Age-related forgetting in locomotor adaptation

    PubMed Central

    Malone, Laura A.; Bastian, Amy J.

    2016-01-01

    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-minute 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 weakens motor memories during rest breaks and that this phenomenon cannot be explained solely by reliance on a conscious strategy in older adults. PMID:26589520

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2010-08-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-09-01

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

  19. 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

  20. 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.

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

    PubMed

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

    2016-01-01

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

  2. 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

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

    PubMed

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

    2013-09-10

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

  4. 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…

  5. 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…

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

    PubMed

    Karniychuk, Uladzimir U

    2016-09-01

    Understanding the codon usage pattern of a pathogen and relationship between pathogen and host's codon usage patterns has fundamental and applied interests. Enterovirus D68 (EV-D68) is an emerging pathogen with a potentially high public health significance. In the present study, the synonymous codon usage bias of 27 recently emerged, and historical EV-D68 strains was analyzed. In contrast to previously studied enteroviruses (enterovirus 71 and poliovirus), EV-D68 and human host have a high discrepancy between favored codons. Analysis of viral synonymous codon usage bias metrics, viral nucleotide/dinucleotide compositional parameters, and viral protein properties showed that mutational pressure is more involved in shaping the synonymous codon usage bias of EV-D68 than translation selection. Computation of codon adaptation indices allowed to estimate expression potential of the EV-D68 genome in several commonly used laboratory animals. This approach requires experimental validation and may provide an auxiliary tool for the rational selection of laboratory animals to model emerging viral diseases. Enterovirus D68 genome compositional and codon usage data can be useful for further pathogenesis, animal model, and vaccine design studies. PMID:27364082

  7. Inflammatory bowel disease related innate immunity and adaptive immunity

    PubMed Central

    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. PMID:27398134

  8. Codon Usage Domains over Bacterial Chromosomes

    PubMed Central

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

    2006-01-01

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

  9. The relative entropy is fundamental to adaptive resolution simulations.

    PubMed

    Kreis, Karsten; Potestio, Raffaello

    2016-07-28

    Adaptive resolution techniques are powerful methods for the efficient simulation of soft matter systems in which they simultaneously employ atomistic and coarse-grained (CG) force fields. In such simulations, two regions with different resolutions are coupled with each other via a hybrid transition region, and particles change their description on the fly when crossing this boundary. Here we show that the relative entropy, which provides a fundamental basis for many approaches in systematic coarse-graining, is also an effective instrument for the understanding of adaptive resolution simulation methodologies. We demonstrate that the use of coarse-grained potentials which minimize the relative entropy with respect to the atomistic system can help achieve a smoother transition between the different regions within the adaptive setup. Furthermore, we derive a quantitative relation between the width of the hybrid region and the seamlessness of the coupling. Our results do not only shed light on the what and how of adaptive resolution techniques but will also help setting up such simulations in an optimal manner. PMID:27475345

  10. The relative entropy is fundamental to adaptive resolution simulations

    NASA Astrophysics Data System (ADS)

    Kreis, Karsten; Potestio, Raffaello

    2016-07-01

    Adaptive resolution techniques are powerful methods for the efficient simulation of soft matter systems in which they simultaneously employ atomistic and coarse-grained (CG) force fields. In such simulations, two regions with different resolutions are coupled with each other via a hybrid transition region, and particles change their description on the fly when crossing this boundary. Here we show that the relative entropy, which provides a fundamental basis for many approaches in systematic coarse-graining, is also an effective instrument for the understanding of adaptive resolution simulation methodologies. We demonstrate that the use of coarse-grained potentials which minimize the relative entropy with respect to the atomistic system can help achieve a smoother transition between the different regions within the adaptive setup. Furthermore, we derive a quantitative relation between the width of the hybrid region and the seamlessness of the coupling. Our results do not only shed light on the what and how of adaptive resolution techniques but will also help setting up such simulations in an optimal manner.

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

    PubMed Central

    Davis, James J.; Olsen, Gary J.

    2010-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Makhija, Aditi; Kumar, Sachin

    2015-12-01

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

  14. Premature termination codons in modern human genomes

    PubMed Central

    Fujikura, Kohei

    2016-01-01

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

  15. Premature termination codons in modern human genomes.

    PubMed

    Fujikura, Kohei

    2016-01-01

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

  16. 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

  17. Codon preferences in free-living microorganisms.

    PubMed Central

    Andersson, S G; Kurland, C G

    1990-01-01

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

  18. 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.

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

    PubMed Central

    Gil, Manuel; Zoller, Stefan; Anisimova, Maria

    2013-01-01

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

  20. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2009-01-01

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

  3. Adaptive functioning in Williams syndrome and its relation to demographic variables and family environment.

    PubMed

    Brawn, Gabrielle; Porter, Melanie

    2014-12-01

    This study assessed adaptive functioning in children and adults with Williams syndrome. The aims were to: (1) profile adaptive functioning; (2) investigate the relationship between adaptive functions and gender, CA, and IQ; (3) investigate the relationship between levels of adaptive functioning and family environment characteristics. In line with predictions: (1) there was extensive variability in adaptive functions; (2) neither gender nor IQ were significantly related to adaptive skills, but Communication skills and Interpersonal Relationship skills failed to make appropriate gains relative to same aged peers and (3) adaptive functioning was significantly related to family environment. Practical and clinical implications are discussed. PMID:25310713

  4. Codon compression algorithms for saturation mutagenesis.

    PubMed

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

    2015-05-15

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

  5. Codon usage trend in mitochondrial CYB gene.

    PubMed

    Uddin, Arif; Chakraborty, Supriyo

    2016-07-15

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

  6. The characteristics of synonymous codon usage in the initial and terminal translation regions of encephalomyocarditis virus.

    PubMed

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

    2014-01-01

    The synonymous codon usage patterns in the initial and terminal translation regions (ITR, TTR) of the whole coding sequence of encephalomyocarditis virus (EMCV) were analyzed in relation to those in its natural hosts using the sequences accessible in databases. In general, some low-usage host codons were found over-represented in the ITR and TTR of the virus, while some high-usage host codons were found under-represented in the two viral regions. These relationships are thought to participate in the regulation of the speed of translation of viral proteins and in the suppression of ribosomal traffic jams, both aiming at the increase of virus yields. PMID:24720745

  7. 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

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

    PubMed

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

    2016-01-01

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

  9. Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins

    PubMed Central

    Goncearenco, Alexander; Ma, Bin-Guang; Berezovsky, Igor N.

    2014-01-01

    DNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea. PMID:24371267

  10. 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.…

  11. Hand gesture recognition by analysis of codons

    NASA Astrophysics Data System (ADS)

    Ramachandra, Poornima; Shrikhande, Neelima

    2007-09-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  13. Computational codon optimization of synthetic gene for protein expression

    PubMed Central

    2012-01-01

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

  14. CodHonEditor: Spreadsheets for Codon Optimization and Editing of Protein Coding Sequences.

    PubMed

    Takai, Kazuyuki

    2016-05-01

    Gene synthesis is getting more important with the growing availability of low-cost commercial services. The coding sequences are often "optimized" as for the relative synonymous codon usage (RSCU) before synthesis, which is generally included in the commercial services. However, the codon optimization processes are different among different providers and are often hidden from the users. Here, the d'Hondt method, which is widely adopted as a method for determining the number of seats for each party in proportional-representation public elections, is applied to RSCU fitting. This allowed me to make a set of electronic spreadsheets for manual design of protein coding sequences for expression in Escherichia coli, with which users can see the process of codon optimization and can manually edit the codons after the automatic optimization. The spreadsheets may also be useful for molecular biology education. PMID:27002987

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

    PubMed

    Sanbonmatsu, K Y; Joseph, S

    2003-04-18

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

  16. Cognitive adaptations for gathering-related navigation in humans

    PubMed Central

    Krasnow, Max M.; Truxaw, Danielle; Gaulin, Steven J.C.; New, Joshua; Ozono, Hiroki; Uono, Shota; Ueno, Taiji; Minemoto, Kazusa

    2013-01-01

    Current research increasingly suggests that spatial cognition in humans is accomplished by many specialized mechanisms, each designed to solve a particular adaptive problem. A major adaptive problem for our hominin ancestors, particularly females, was the need to efficiently gather immobile foods which could vary greatly in quality, quantity, spatial location and temporal availability. We propose a cognitive model of a navigational gathering adaptation in humans and test its predictions in samples from the US and Japan. Our results are uniformly supportive: the human mind appears equipped with a navigational gathering adaptation that encodes the location of gatherable foods into spatial memory. This mechanism appears to be chronically active in women and activated under explicit motivation in men. PMID:23833551

  17. 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

  18. Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR.

    PubMed

    Kianmehr, Anvarsadat; Golavar, Raziyeh; Rouintan, Mandana; Mahrooz, Abdolkarim; Fard-Esfahani, Pezhman; Oladnabi, Morteza; Khajeniazi, Safoura; Mostafavi, Seyede Samaneh; Omidinia, Eskandar

    2016-02-01

    Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse-transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC% content changed from 56% to 58%. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa. PMID:26546410

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

    PubMed

    Whittle, Carrie A; Extavour, Cassandra G

    2015-11-01

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

  20. 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

  1. 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…

  2. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli

    PubMed Central

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

  3. Pangenome Evidence for Higher Codon Usage Bias and Stronger Translational Selection in Core Genes of Escherichia coli.

    PubMed

    Sun, Shixiang; Xiao, Jingfa; Zhang, Huiyong; Zhang, Zhang

    2016-01-01

    Codon usage bias, as a combined interplay from mutation and selection, has been intensively studied in Escherichia coli. However, codon usage analysis in an E. coli pangenome remains unexplored and the relative importance of mutation and selection acting on core genes and strain-specific genes is unknown. Here we perform comprehensive codon usage analyses based on a collection of multiple complete genome sequences of E. coli. Our results show that core genes that are present in all strains have higher codon usage bias than strain-specific genes that are unique to single strains. We further explore the forces in influencing codon usage and investigate the difference of the major force between core and strain-specific genes. Our results demonstrate that although mutation may exert genome-wide influences on codon usage acting similarly in different gene sets, selection dominates as an important force to shape biased codon usage as genes are present in an increased number of strains. Together, our results provide important insights for better understanding genome plasticity and complexity as well as evolutionary mechanisms behind codon usage bias. PMID:27536275

  4. 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…

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

    PubMed

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

    2015-08-01

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

  6. 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

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

    PubMed Central

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

    1984-01-01

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

  8. 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

  9. 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

  10. Big Data, Evolution, and Metagenomes: Predicting Disease from Gut Microbiota Codon Usage Profiles.

    PubMed

    Fabijanić, Maja; Vlahoviček, Kristian

    2016-01-01

    Metagenomics projects use next-generation sequencing to unravel genetic potential in microbial communities from a wealth of environmental niches, including those associated with human body and relevant to human health. In order to understand large datasets collected in metagenomics surveys and interpret them in context of how a community metabolism as a whole adapts and interacts with the environment, it is necessary to extend beyond the conventional approaches of decomposing metagenomes into microbial species' constituents and performing analysis on separate components. By applying concepts of translational optimization through codon usage adaptation on entire metagenomic datasets, we demonstrate that a bias in codon usage present throughout the entire microbial community can be used as a powerful analytical tool to predict for community lifestyle-specific metabolism. Here we demonstrate this approach combined with machine learning, to classify human gut microbiome samples according to the pathological condition diagnosed in the human host. PMID:27115650

  11. 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

  12. The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

    PubMed Central

    Sengupta, Supratim; Yang, Xiaoguang

    2007-01-01

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

  13. 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

  14. Adapting Law-Related Education to Juvenile Justice Settings.

    ERIC Educational Resources Information Center

    Curd-Larkin, Mary C.

    1987-01-01

    Notes that juvenile justice systems are increasingly turning to law-related education (LRE) programs as a means of providing youths with some of the skills and knowledge which might deter continued delinquent behavior. Describes issues which must be addressed when implementing LRE in juvenile justice settings. (JDH)

  15. 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

  16. 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

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

    PubMed

    Wohlin, Åsa

    2015-03-21

    The distribution of codons in the nearly universal genetic code is a long discussed issue. At the atomic level, the numeral series 2x(2) (x=5-0) lies behind electron shells and orbitals. Numeral series appear in formulas for spectral lines of hydrogen. The question here was if some similar scheme could be found in the genetic code. A table of 24 codons was constructed (synonyms counted as one) for 20 amino acids, four of which have two different codons. An atomic mass analysis was performed, built on common isotopes. It was found that a numeral series 5 to 0 with exponent 2/3 times 10(2) revealed detailed congruency with codon-grouped amino acid side-chains, simultaneously with the division on atom kinds, further with main 3rd base groups, backbone chains and with codon-grouped amino acids in relation to their origin from glycolysis or the citrate cycle. Hence, it is proposed that this series in a dynamic way may have guided the selection of amino acids into codon domains. Series with simpler exponents also showed noteworthy correlations with the atomic mass distribution on main codon domains; especially the 2x(2)-series times a factor 16 appeared as a conceivable underlying level, both for the atomic mass and charge distribution. Furthermore, it was found that atomic mass transformations between numeral systems, possibly interpretable as dimension degree steps, connected the atomic mass of codon bases with codon-grouped amino acids and with the exponent 2/3-series in several astonishing ways. Thus, it is suggested that they may be part of a deeper reference system. PMID:25623487

  18. Age-related changes in the adaptability of neuromuscular output.

    PubMed

    Morrison, Steven; Sosnoff, Jacob J

    2009-05-01

    The aging process is associated with a general decline in biological function. One characteristic that researchers believe represents this diminished functioning of the aging neuromuscular system is increased physiological tremor. The present study is constructed to assess what age-related differences exist in the dynamics of tremor and forearm muscle activity under postural conditions in which the number of arm segments involved in the task was altered. The authors predicted that any alteration in the tremor or electromyographic (EMG) output of these two groups would provide a clearer understanding of the differential effects of aging or task dynamics on physiological function. Results reveal no age-related differences in finger tremor or forearm extensor muscle EMG activity under conditions in which participants were only required to extend their index finger against gravity. However, when participants had to hold their entire upper limb steady against gravity, the authors observed significant increases in forearm EMG activity, finger-tremor amplitude, power in the 8-12-Hz range, and signal regularity between the 2 age groups. The selective changes in signal regularity, EMG activity, and 8-12-Hz tremor amplitude under more challenging postural demands support the view that the age-related changes in neuromuscular dynamics are not fully elucidated when single task demands are utilized. PMID:19366659

  19. 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

  20. 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

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

    PubMed

    Sirotkin, K

    1988-04-01

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

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

    PubMed Central

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

    2005-01-01

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

  3. 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

  4. An empirical test of the concomitantly variable codon hypothesis

    PubMed Central

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

    2007-01-01

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

  5. 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

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

    PubMed

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

    2014-02-01

    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

  7. Nonsense codons trigger an RNA partitioning shift.

    PubMed

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

    2009-02-13

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

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

    PubMed

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

    2013-04-01

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

  9. 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

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

    PubMed

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

    2014-09-01

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

  11. 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

  12. 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. PMID:25459295

  13. Physiology-driven adaptive virtual reality stimulation for prevention and treatment of stress related disorders.

    PubMed

    Cosić, Kresimir; Popović, Sinisa; Kukolja, Davor; Horvat, Marko; Dropuljić, Branimir

    2010-02-01

    The significant proportion of severe psychological problems related to intensive stress in recent large peacekeeping operations underscores the importance of effective methods for strengthening the prevention and treatment of stress-related disorders. Adaptive control of virtual reality (VR) stimulation presented in this work, based on estimation of the person's emotional state from physiological signals, may enhance existing stress inoculation training (SIT). Physiology-driven adaptive VR stimulation can tailor the progress of stressful stimuli delivery to the physiological characteristics of each individual, which is indicated for improvement in stress resistance. Following an overview of physiology-driven adaptive VR stimulation, its major functional subsystems are described in more detail. A specific algorithm of stimuli delivery applicable to SIT is outlined. PMID:20528296

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

    PubMed

    Kessler, Michael D; Dean, Matthew D

    2014-10-01

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

  15. 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

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

    PubMed

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

    2015-05-01

    Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease. PMID:25839760

  17. Effects of codon modification on human BMP2 gene expression in tobacco plants.

    PubMed

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Duan, Ziyuan; He, Zhengquan; Yao, Wei; Yue, Chaoyin; Dai, Jianwu

    2006-07-01

    Bone morphogenetic protein 2 (BMP2) has great potential in therapeutic applications. We are working on generating transgenic plants as a bioreactor to produce BMP2. We have studied the effects of codon optimization on the expression of human BMP2 (hBMP2) in tobacco plants. Three modified hBMP2 genes were transformed into tobacco under the control of either cauliflower mosaic virus 35S (CaMV35S) promoter or double-CaMV35S promoter plus alfalfa mosaic virus (AMV) enhancer. The fused beta-glucuronidase (GUS) reporter gene was used to facilitate the assay of protein expression. The results indicated that codon optimization could increase the protein expression level obviously under CaMV35S promoter. However, under relatively stronger initiation condition (double-CaMV35S promoter plus AMV enhancer), only the gene with the lowest degree of codon optimization could increase the protein expression level. Our findings suggest that the action of codon optimization may be influenced by the factors of promoter strength and A+T content in tobacco plants. PMID:16491379

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

    PubMed

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

    2016-05-22

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

  19. Adaptive, maladaptive, mediational, and bidirectional processes of relational and physical aggression, relational and physical victimization, and peer liking.

    PubMed

    Kawabata, Yoshito; Tseng, Wan-Ling; Crick, Nicki R

    2014-01-01

    A three-wave longitudinal study among ethnically diverse preadolescents (N = 597 at Time 1, ages 9-11) was conducted to examine adaptive, maladaptive, mediational, and bidirectional processes of relational and physical aggression, victimization, and peer liking indexed by peer acceptance and friendships. A series of nested structural equation models tested the hypothesized links among these peer-domain factors. It was hypothesized that (1) relational aggression trails both adaptive and maladaptive processes, linking to more peer victimization and more peer liking, whereas physical aggression is maladaptive, resulting in more peer victimization and less peer liking; (2) physical and relational victimization is maladaptive, relating to more aggression and less peer liking; (3) peer liking may be the social context that promotes relational aggression (not physical aggression), whereas peer liking may protect against peer victimization, regardless of its type; and (4) peer liking mediates the link between forms of aggression and forms of peer victimization. Results showed that higher levels of peer liking predicted relative increases in relational aggression (not physical aggression), which in turn led to more peer liking. On the other hand, more peer liking was predictive of relative decreases in relational aggression and relational victimization in transition to the next grade (i.e., fifth grade). In addition, relational victimization predicted relative increases in relational aggression and relative decreases in peer liking. Similarly, physical aggression was consistently and concurrently associated more physical victimization and was marginally predictive of relative increases in physical victimization in transition to the next grade. More peer liking predicted relative decreases in physical victimization, which resulted in lower levels of peer liking. The directionality and magnitude of these paths did not differ between boys and girls. PMID:24318459

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

    PubMed

    Dohra, Hideo; Fujishima, Masahiro; Suzuki, Haruo

    2015-10-01

    The ciliate Paramecium bursaria harbors the green-alga Chlorella symbionts. We reassembled the P. bursaria transcriptome to minimize falsely fused transcripts, and investigated amino acid and codon usage using the transcriptome data. Surface proteins preferentially use smaller amino acid residues like cysteine. Unusual synonymous codon and amino acid usage in highly expressed genes can reflect a balance between translational selection and other factors. A correlation of gene expression level with synonymous codon or amino acid usage is emphasized in genes down-regulated in symbiont-bearing cells compared to symbiont-free cells. Our results imply that the selection is associated with P. bursaria-Chlorella symbiosis. PMID:26341535

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed Central

    2013-01-01

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

  8. 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

    2016-01-01

    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. PMID:26909997

  9. Highly reproductive Escherichia coli cells with no specific assignment to the UAG codon

    PubMed Central

    Mukai, Takahito; Hoshi, Hiroko; Ohtake, Kazumasa; Takahashi, Mihoko; Yamaguchi, Atsushi; Hayashi, Akiko; Yokoyama, Shigeyuki; Sakamoto, Kensaku

    2015-01-01

    Escherichia coli is a widely used host organism for recombinant technology, and the bacterial incorporation of non-natural amino acids promises the efficient synthesis of proteins with novel structures and properties. In the present study, we developed E. coli strains in which the UAG codon was reserved for non-natural amino acids, without compromising the reproductive strength of the host cells. Ninety-five of the 273 UAG stop codons were replaced synonymously in the genome of E. coli BL21(DE3), by exploiting the oligonucleotide-mediated base-mismatch-repair mechanism. This genomic modification allowed the safe elimination of the UAG-recognizing cellular component (RF-1), thus leaving the remaining 178 UAG codons with no specific molecule recognizing them. The resulting strain B-95.ΔA grew as vigorously as BL21(DE3) in rich medium at 25–42°C, and its derivative B-95.ΔAΔfabR was better adapted to low temperatures and minimal media than B-95.ΔA. UAG was reassigned to synthetic amino acids by expressing the specific pairs of UAG-reading tRNA and aminoacyl-tRNA synthetase. Due to the preserved growth vigor, the B-95.ΔA strains showed superior productivities for hirudin molecules sulfonated on a particular tyrosine residue, and the Fab fragments of Herceptin containing multiple azido groups. PMID:25982672

  10. Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

    PubMed Central

    Miyazawa, Sanzo

    2011-01-01

    Background Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Results Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. Conclusions/Significance The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences. PMID:21445250

  11. Bicluster Pattern of Codon Context Usages between Flavivirus and Vector Mosquito Aedes aegypti: Relevance to Infection and Transcriptional Response of Mosquito Genes

    PubMed Central

    Behura, Susanta K.; Severson, David W.

    2014-01-01

    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 inusages 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 contexts bias in evolution of vector-virus interactions at the molecular level. PMID:24838953

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

    PubMed

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

    2016-03-01

    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

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

    PubMed

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

    2016-07-01

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

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

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

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

  15. Self-regulation and its relations to adaptive functioning in low income youths.

    PubMed

    Buckner, John C; Mezzacappa, Enrico; Beardslee, William R

    2009-01-01

    Most studies of self-regulation involving children have linked it to specific outcomes within a single domain of adaptive functioning. The authors examined the association of self-regulation with a range of indices of adaptive functioning among 155 youth ages 8-18 years from families with very low income. Controlling for other explanatory variables, self-regulation was strongly associated with various outcome measures in the areas of mental health, behavior, academic achievement, and social competence. The authors also contrasted youths relatively high and low in self-regulation (the top and bottom quartiles). Youths with good self-regulation had much better indices of adaptive functioning across measures of social competence, academic achievement, grades, problem behaviors, and depression and anxiety than their counterparts with more diminished self-regulatory capacities. In addition, youths with better self-regulation skills stated more adaptive responses both in terms of how they coped with past stressful live events and how they would deal with hypothetical stressors. This study indicates that self-regulation is robustly associated with a range of important indices of adaptive functioning across many domains. Findings are discussed in light of their implications for theory and intervention for children of diverse economic backgrounds. PMID:19290722

  16. 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…

  17. Relational Benefits of Relational Aggression: Adaptive and Maladaptive Associations with Adolescent Friendship Quality

    ERIC Educational Resources Information Center

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

    2011-01-01

    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…

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

    PubMed

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

    2015-12-01

    The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome. PMID:26797435

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

    PubMed Central

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

    2015-01-01

    The tapeworm Taenia solium is an important human zoonotic parasite that causes great economic loss and also endangers public health. At present, an effective vaccine that will prevent infection and chemotherapy without any side effect remains to be developed. In this study, codon usage patterns in the T. solium genome were examined through 8,484 protein-coding genes. Neutrality analysis showed that T. solium had a narrow GC distribution, and a significant correlation was observed between GC12 and GC3. Examination of an NC (ENC vs GC3s)-plot showed a few genes on or close to the expected curve, but the majority of points with low-ENC (the effective number of codons) values were detected below the expected curve, suggesting that mutational bias plays a major role in shaping codon usage. The Parity Rule 2 plot (PR2) analysis showed that GC and AT were not used proportionally. We also identified 26 optimal codons in the T. solium genome, all of which ended with either a G or C residue. These optimal codons in the T. solium genome are likely consistent with tRNAs that are highly expressed in the cell, suggesting that mutational and translational selection forces are probably driving factors of codon usage bias in the T. solium genome. PMID:26797435

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

    PubMed Central

    Cao, Liaoran; Li, Guohui; Cheng, Hong

    2016-01-01

    Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5’ ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer. PMID:26840415

  1. 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites.

    PubMed

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

    2002-12-01

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

  2. 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. PMID:26993103

  3. 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

  4. 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

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

    PubMed

    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

  6. 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

  7. On the relationship between human sensorimotor adaptability and event-related potentials.

    PubMed

    Dinh, Tram Hong; Jansen, Ben H

    2011-06-01

    It was explored if the speed with which an individual learns to deal with new environments and challenges can be predicted on the basis of his/her brain's response to irrelevant (repeating) and novel auditory stimuli. In this study, 26 subjects threw 30 light-weight balls at a target with and without vision-distorting goggles. The horizontal displacement from a bull's-eye target was measured and the rate and degree of adaptation were computed. The adaptation parameters were correlated with evoked and event-related potential (EP/ERP) measures of the subject's ability to suppress irrelevant information and respond to novel stimuli. Only a weak (or a trend to) correlation was found between the behavioral adaptation and some of the EP/ERP measures. The correlations were limited to EP parameters in the 100 to 200 ms post-stimulus range reflecting the ability to suppress irrelevant information. Thus we conclude that the speed with which an individual adapts to a new environment is at best weakly correlated with brain activity associated with stimulus memory and classification. PMID:21714139

  8. Adaptive differentiation of traits related to resource use in a desert annual along a resource gradient.

    PubMed

    Brouillette, Larry C; Mason, Chase M; Shirk, Rebecca Y; Donovan, Lisa A

    2014-03-01

    • Plant resource-use traits are generally hypothesized to be adaptively differentiated for populations distributed along resource gradients. Although nutrient limitations are expected to select for resource-conservative strategies, water limitations may select for either resource-conservative or -acquisitive strategies. We test whether population differentiation reflects local adaptation for traits associated with resource-use strategies in a desert annual (Helianthus anomalus) distributed along a gradient of positively covarying water and nutrient availability. • We compared quantitative trait variation (Q(ST)) with neutral genetic differentiation (F(ST)), in a common garden glasshouse study, for leaf economics spectrum (LES) and related traits: photosynthesis (A(mass), A(area)), leaf nitrogen (N(mass), N(area)), leaf lifetime (LL), leaf mass per area (LMA), leaf water content (LWC), water-use efficiency (WUE, estimated as δ(13)C) and days to first flower (DFF). • Q(ST)-F(ST) differences support adaptive differentiation for Amass , N(mass), N(area), LWC and DFF. The trait combinations associated with drier and lower fertility sites represent correlated trait evolution consistent with the more resource-acquisitive end of the LES. There was no evidence for adaptive differentiation for A(area), LMA and WUE. • These results demonstrate that hot dry environments can selectively favor correlated evolution of traits contributing to a resource-acquisitive and earlier reproduction 'escape' strategy, despite lower fertility. PMID:24325125

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

    PubMed

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

    2002-06-01

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

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

    PubMed

    Pluhar, Wolfgang

    2006-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. K-ras mutation at codon 12 in stage I pancreatic adenocarcinoma: analysis by laser capture microdissection and direct sequencing.

    PubMed

    Chang, M C; Chang, Y T; Wu, M S; Shun, C T; Tien, Y W; Lin, J T

    2001-05-01

    Pancreatic ductal adenocarcinoma has been reported to carry a rate mutation high in codon 12 of the K-ras oncogene. To avoid the pitfalls of conventional methods of tissue dissection that might affect the sensitivity and specificity of detecting K-ras mutation, laser capture microdissection (LCM) technique was used. Pancreatic adenocarcinoma tissues were obtained from 15 patients who underwent Whipple's procedure. Selected tissues procured by LCM were analyzed by direct sequencing after polymerase chain reaction amplification of K-ras sequences at codon 12. K-ras mutation was noted in nine patients. All mutations showed G to A substitution at codon 12. The mutational pattern (GGT to GAT) is similar in both western and eastern reports. LCM is a feasible method to effectively obtain pure tumor cells from a surgical specimen. It remains to be determined whether this low mutation rate is a result of relatively early stage of disease or different carcinogenesis in different geographic regions. PMID:11432318

  14. 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

  15. A Comprehensive MicroRNA Expression Profile Related to Hypoxia Adaptation in the Tibetan Pig.

    PubMed

    Zhang, Bo; Qiangba, Yangzong; Shang, Peng; Wang, Zhixiu; Ma, Jun; Wang, Liyuan; Zhang, Hao

    2015-01-01

    Tibetan pigs live between 2500 and 4300 m above sea level on the Tibetan Plateau, and are better adapted to hypoxia than lowland pigs. MicroRNAs (miRNAs) are involved in a wide variety of cellular processes; however, their regulatory role in hypoxia adaptation remains unclear. In this study, miRNA-seq was used to identify differentially expressed miRNAs (DE miRNAs) in the cardiac muscle of Tibetan and Yorkshire pigs, which were both raised in high elevation environments. We obtained 108 M clean reads and 372 unique miRNAs, which included 210 known porcine miRNAs, 136 conserved in other mammals, and 26 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 up-regulated and 10 down-regulated miRNAs, were also found after comparison between Tibetan and Yorkshire pigs. We predicted miRNA targets based on differential expression and abundance in the two populations. Furthermore, the results of a Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that DE miRNAs in Tibetan and Yorkshire pigs are involved in hypoxia-related signaling pathways such as the mitogen-activated protein kinase, which is the mechanistic target of rapamycin, and the vascular endothelial growth factor, as well as cancer-related signaling pathways. Five DE miRNAs were randomly selected to validate the results of miRNA-seq using real-time polymerase chain reaction, and the results corresponded to those from the miRNA-seq, confirming that deep-sequencing methods are feasible and efficient. In our study, we identified various previously unknown hypoxia-related miRNAs in pigs, and the data obtained suggest that hypoxia-related miRNA expression patterns are significantly altered in the Tibetan pig compared to other species. Therefore, DE miRNAs may play an important role in organisms that have adapted to hypoxic environments. PMID:26571238

  16. A Comprehensive MicroRNA Expression Profile Related to Hypoxia Adaptation in the Tibetan Pig

    PubMed Central

    Shang, Peng; Wang, Zhixiu; Ma, Jun; Wang, Liyuan; Zhang, Hao

    2015-01-01

    Tibetan pigs live between 2500 and 4300 m above sea level on the Tibetan Plateau, and are better adapted to hypoxia than lowland pigs. MicroRNAs (miRNAs) are involved in a wide variety of cellular processes; however, their regulatory role in hypoxia adaptation remains unclear. In this study, miRNA-seq was used to identify differentially expressed miRNAs (DE miRNAs) in the cardiac muscle of Tibetan and Yorkshire pigs, which were both raised in high elevation environments. We obtained 108 M clean reads and 372 unique miRNAs, which included 210 known porcine miRNAs, 136 conserved in other mammals, and 26 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 up-regulated and 10 down-regulated miRNAs, were also found after comparison between Tibetan and Yorkshire pigs. We predicted miRNA targets based on differential expression and abundance in the two populations. Furthermore, the results of a Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that DE miRNAs in Tibetan and Yorkshire pigs are involved in hypoxia-related signaling pathways such as the mitogen-activated protein kinase, which is the mechanistic target of rapamycin, and the vascular endothelial growth factor, as well as cancer-related signaling pathways. Five DE miRNAs were randomly selected to validate the results of miRNA-seq using real-time polymerase chain reaction, and the results corresponded to those from the miRNA-seq, confirming that deep-sequencing methods are feasible and efficient. In our study, we identified various previously unknown hypoxia-related miRNAs in pigs, and the data obtained suggest that hypoxia-related miRNA expression patterns are significantly altered in the Tibetan pig compared to other species. Therefore, DE miRNAs may play an important role in organisms that have adapted to hypoxic environments. PMID:26571238

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

    PubMed

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

    2016-08-19

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

  18. 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.

  19. 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.

  20. 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.

  1. Factors Related to Adaptation to Cystectomy With Urinary Diversion: An Integrative Review.

    PubMed

    Merandy, Kyle

    2016-01-01

    Patients with bladder (urothelial) cancer undergoing urinary diversion (UD) experience physical changes that require important adjustments in their daily lives. This integrative review aims to identify factors that influence adult adaptation to life after cystectomy with the creation of a UD. A review of primary research articles published between 1990 and 2014 was conducted using the PubMed and CINAHL Plus electronic databases. Results of the studies were summarized into 5 categories: (1) individual and family factors, (2) technical aspects related to the individual's ability to care for his or her UD, (3) perioperative nursing care, (4) educational needs, and (5) symptom experience. Bladder cancer patients treated with a cystectomy with a UD have a complex set of needs during postoperative adaptation to their reconstructed urinary system. This integrative review summarizes existing knowledge of factors that affect adaptation to a UD in patients with bladder cancer and may guide future studies. Research on this is limited and more studies are needed. PMID:27607746

  2. 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. PMID:25419980

  3. 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

  4. 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. PMID:21306459

  5. Prenatal and Perinatal Factors Related to Autism, IQ, and Adaptive Functioning.

    PubMed

    Perrone-McGovern, Kristin; Simon-Dack, Stephanie; Niccolai, Lindsay

    2015-01-01

    This study focused on prenatal and perinatal factors related to autism spectrum disorder (ASD). The authors hypothesized that mothers who exposed their infants to intrauterine toxicity or who had complications with labor or delivery would be more likely to give birth to individuals with lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. This clinical sample consisted of 33 children who presented for neuropsychological assessment with symptoms of ASD. Results indicated that individuals with a history of intrauterine toxicity had lower IQ scores than individuals who did not have a history of intrauterine toxicity. However, no significant effects were found for intrauterine toxicity and ASD or adaptive functioning. Results indicated that individuals with a history of complications during labor and delivery had lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. Findings may lend support to the oxidative stress theory of ASD. PMID:25608037

  6. A backtranslation method based on codon usage strategy.

    PubMed Central

    Pesole, G; Attimonelli, M; Liuni, S

    1988-01-01

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

  7. 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. PMID:27195118

  8. 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

  9. 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.

  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)

    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.

  11. 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…

  12. 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

  13. 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

  14. 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

  15. Double Trouble at High Density: Cross-Level Test of Resource-Related Adaptive Plasticity and Crowding-Related Fitness

    PubMed Central

    Gergs, André; Preuss, Thomas G.; Palmqvist, Annemette

    2014-01-01

    Population size is often regulated by negative feedback between population density and individual fitness. At high population densities, animals run into double trouble: they might concurrently suffer from overexploitation of resources and also from negative interference among individuals regardless of resource availability, referred to as crowding. Animals are able to adapt to resource shortages by exhibiting a repertoire of life history and physiological plasticities. In addition to resource-related plasticity, crowding might lead to reduced fitness, with consequences for individual life history. We explored how different mechanisms behind resource-related plasticity and crowding-related fitness act independently or together, using the water flea Daphnia magna as a case study. For testing hypotheses related to mechanisms of plasticity and crowding stress across different biological levels, we used an individual-based population model that is based on dynamic energy budget theory. Each of the hypotheses, represented by a sub-model, is based on specific assumptions on how the uptake and allocation of energy are altered under conditions of resource shortage or crowding. For cross-level testing of different hypotheses, we explored how well the sub-models fit individual level data and also how well they predict population dynamics under different conditions of resource availability. Only operating resource-related and crowding-related hypotheses together enabled accurate model predictions of D. magna population dynamics and size structure. Whereas this study showed that various mechanisms might play a role in the negative feedback between population density and individual life history, it also indicated that different density levels might instigate the onset of the different mechanisms. This study provides an example of how the integration of dynamic energy budget theory and individual-based modelling can facilitate the exploration of mechanisms behind the regulation

  16. 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

    2014-01-01

    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

  17. 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

  18. 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. PMID:26767379

  19. 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

  20. 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

  1. Relative crystallinity of plant biomass: studies on assembly, adaptation and acclimation.

    PubMed

    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

  2. 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

  3. Codon optimization, expression, purification, and functional characterization of recombinant human IL-25 in Pichia pastoris.

    PubMed

    Liu, Yushan; Wu, Chengsheng; Wang, Jinyu; Mo, Wei; Yu, Min

    2013-12-01

    Interleukin (IL)-25 (also known as IL-17E) is a distinct member of the IL-17 cytokine family which induces IL-4, IL-5, and IL-13 expression and promotes pathogenic T helper (Th)-2 cell responses in various organs. IL-25 has been shown to have crucial role between innate and adaptive immunity and also a key component of the protection of gastrointestinal helminthes. In this study, to produce bioactive recombinant human IL-25 (rhIL-25), the cDNA of mature IL-25 was performed codon optimization based on methylotropic yeast Pichia pastoris codon bias and cloned into the expression vector pPICZαA. The recombinant vector was transformed into P. pichia strain X-33 and selected by zeocin resistance. Benchtop fermentation and simple purification strategy were established to purify the rhIL-25 with about 17 kDa molecular mass. Functional analysis showed that purified rhIL-25 specifically bond to receptor IL-17BR and induce G-CSF production in vitro. Further annexin V-FITC/PI staining assay indicated that rhIL-25 induced apoptosis in two breast cancer cells, MDA-MB-231 and HBL-100. This study provides a new strategy for the large-scale production of bioactive IL-25 for biological and therapeutic applications. PMID:24100683

  4. 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. PMID:25630906

  5. 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, III; 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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…

  11. 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. PMID:24964213

  12. 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

  13. 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…

  14. An adaptive governance approach to disaster-related behavioural health services.

    PubMed

    Andrew, Simon A; Kendra, James M

    2012-07-01

    This paper explores the provision of disaster-related behavioural and mental health (DBH) services as a problem of institutional collective action in the United States. This study reviews the challenges that providers have in surmounting multi-organizational disconnects, unstable professional legitimacy, ambiguous information, and shifting disaster needs in developing a system for delivering DBH services. Based on the adaptive governance framework, it argues that existing protocols such as the National Incident Management System (NIMS) and Incident Command System (ICS) may be helpful in advancing collective action, but that real progress will depend on a recognition of norms, expectations, and credentials across many spheres-in other words, on the ability of responders to continuously adjust their procedures and administrative boundaries for behavioural health institutions. PMID:22066735

  15. Investigation of age-related differences in an adapted Hayling task.

    PubMed

    Tournier, Isabelle; Postal, Virginie; Mathey, Stéphanie

    2014-01-01

    The Hayling task is traditionally used to assess activation and inhibitory processes efficiency among various populations, such as elderly adults. However, the classical design of the task may also involve the influence of strategy use and efficiency of sentence processing in the possible differences between individuals. Therefore, the present study investigated activation and inhibitory processes in aging with two formats of an adapted Hayling task designed to reduce the involvement of these alternative factors. Thirty young adults (M=20.7 years) and 31 older adults (M=69.6 years) performed an adapted Hayling task including a switching block (i.e., unblocked design) in addition to the classical task (i.e., blocked design), and the selection of the response between two propositions. The results obtained with the classical blocked design showed age-related deficits in the suppression sections of the task but also in the initiation ones. These findings can be explained by a co-impairment of both inhibition and activation processes in aging. The results of the unblocked Hayling task, in which strategy use would be reduced, confirmed this age-related decline in both activation and inhibition processes. Moreover, significant correlations between the unblocked design and the Trail Making Test revealed that flexibility is equally involved in the completion of both sections of this design. Finally, the use of a forced-response choice offers a format that is easy to administer to people with normal or pathological aging. This seems particularly relevant for these populations in whom the production of an unrelated word often poses problems. PMID:25139228

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

    PubMed Central

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

    2013-01-01

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

  17. 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…

  18. 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. PMID:27017544

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

    PubMed Central

    He, Shan L.; Green, Rachel

    2010-01-01

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

  20. Decoding RAS isoform and codon-specific signalling

    PubMed Central

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

    2014-01-01

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

  1. 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

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

    PubMed

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

    2016-08-19

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

  3. Agouti-related peptide neural circuits mediate adaptive behaviors in the starved state.

    PubMed

    Padilla, Stephanie L; Qiu, Jian; Soden, Marta E; Sanz, Elisenda; Nestor, Casey C; Barker, Forrest D; Quintana, Albert; Zweifel, Larry S; Rønnekleiv, Oline K; Kelly, Martin J; Palmiter, Richard D

    2016-05-01

    In the face of starvation, animals will engage in high-risk behaviors that would normally be considered maladaptive. Starving rodents, for example, will forage in areas that are more susceptible to predators and will also modulate aggressive behavior within a territory of limited or depleted nutrients. The neural basis of these adaptive behaviors likely involves circuits that link innate feeding, aggression and fear. Hypothalamic agouti-related peptide (AgRP)-expressing neurons are critically important for driving feeding and project axons to brain regions implicated in aggression and fear. Using circuit-mapping techniques in mice, we define a disynaptic network originating from a subset of AgRP neurons that project to the medial nucleus of the amygdala and then to the principal bed nucleus of the stria terminalis, which suppresses territorial aggression and reduces contextual fear. We propose that AgRP neurons serve as a master switch capable of coordinating behavioral decisions relative to internal state and environmental cues. PMID:27019015

  4. 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. PMID:24146305

  5. 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

  6. 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.

  7. Lower mitochondrial DNA content relates to high-altitude adaptation in Tibetans.

    PubMed

    Li, Yue; Huang, Wei; Yu, Qin; Cheng, Yao-Ting; Kong, Qing-Peng

    2016-01-01

    Mitochondrial DNA (mtDNA) is crucial to mitochondria in energy production and other physiological functions. When lowlanders arrive at high altitude, the mitochondrial content tends to decrease. However, the mtDNA content of native highlanders share the same feature as lowlanders remains unknown. It is also interesting to dissect the other changes in blood plasma that might accompany the change of mtDNA content. To address these issues, we recruited 241 Tibetan subjects in Tibet and 220 Han subjects in Shaanxi province. Relative mtDNA copy number and blood biochemical indexes were measured. Results show that relative mtDNA copy number in Tibetans is significantly lower as compared to Han subjects; sex, age, blood glucose, triglyceride and total cholesterol show no influence on mtDNA content, but carbon dioxide combining power is negatively correlated with mtDNA content. These results indicate that an increase in CO2 combining power along with lower mtDNA content may provide adaptive potential. PMID:24845439

  8. Adaptive style and differences in parent and child report of health-related quality of life in children with cancer.

    PubMed

    Jurbergs, Nichole; Russell, Kathryn M W; Long, Alanna; Phipps, Sean

    2008-01-01

    The objective of this study was to examine the self-reported health-related quality of life (HRQL) of children with cancer, and the consistency between child and parent reports of child HRQL, as a function of the child's adaptive style. Participants included 199 children with cancer, 108 healthy children, and their parents. Children completed self-report measures of HRQL and adaptive style. Measures of adaptive style were used to categorize children as high anxious, low anxious, defensive high anxious or repressor. Parents completed measures reporting their children's HRQL. Adaptive style was a significant predictor of child-reported HRQL, particularly on the psychosocial scales, with children identified as repressors reporting the best HRQL. Adaptive style was also predictive of discrepancies between parent and child report of child HRQL. Repressor and low anxious children reported better HRQL than did their parents, while high anxious children reported poorer HRQL, regardless of health status. Adaptive style is a significant determinant of self-reported HRQL in children, particularly in psychosocial domains, while health status (i.e. cancer patient vs healthy control) is predictive only of physical health domains. Researchers and clinicians should be aware of the impact of child adaptive style when assessing HRQL outcomes using self- or parent report. PMID:17410520

  9. 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

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2016-08-01

    Bacteria and archaea have evolved with the ability to fix atmospheric dinitrogen in the form of ammonia, catalyzed by the nitrogenase enzyme complex which comprises three structural genes nifK, nifD and nifH. The nifK and nifD encodes for the beta and alpha subunits, respectively, of component 1, while nifH encodes for component 2 of nitrogenase. Phylogeny based on nifDHK have indicated that Cyanobacteria is closer to Proteobacteria alpha and gamma but not supported by the tree based on 16SrRNA. The evolutionary ancestor for the different trees was also different. The GC1 and GC2% analysis showed more consistency than GC3% which appeared to below for Firmicutes, Cyanobacteria and Euarchaeota while highest in Proteobacteria beta and clearly showed the proportional effect on the codon usage with a few exceptions. Few genes from Firmicutes, Euryarchaeota, Proteobacteria alpha and delta were found under mutational pressure. These nif genes with low and high GC3% from different classes of organisms showed similar expected number of codons. Distribution of the genes and codons, based on codon usage demonstrated opposite pattern for different orientation of mirror plane when compared with each other. Overall our results provide a comprehensive analysis on the evolutionary relationship of the three structural nif genes, nifK, nifD and nifH, respectively, in the context of codon usage bias, GC content relationship and amino acid composition of the encoded proteins and exploration of crucial statistical method for the analysis of positive data with non-constant variance to identify the shape factors of codon adaptation index. PMID:26309237

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. 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

  15. 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. PMID:26162887

  16. 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.

  17. 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. PMID:26019162

  18. 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

  19. Cross-cultural adaptation and validation of the voice-related quality of life into Persian.

    PubMed

    Moradi, Negin; Saki, Nader; Aghadoost, Ozra; Nikakhlagh, Soheila; Soltani, Majid; Derakhshandeh, Vita; Naderifar, Ehsan; Mahmoodi Bakhtiari, Behrooz; Javadipour, Shiva

    2014-11-01

    The purpose of this study was to adapt and determine reliability, validity, and responsiveness of voice-related quality of life (V-RQOL) for Persian. A total of 300 patients with voice disorders participated in the study. Also, 116 people without any voice disorders volunteered to participate in the study as a control group. All participants filled in the Persian version of V-RQOL. The reliability, validity, and responsiveness were studied. Results demonstrated that the discrimination coefficient is significant for all items. The V-RQOL measure showed a strong internal consistency (Cronbach alpha coefficient = 0.88-0.91) and a good test-retest reliability (r = 0.93-0.95). Pre- and post-treatment results showed a significant responsiveness (functioning, 0.000; social-emotional, 0.001; and total, 0.000). Effect size range of 1.26-1.59 and the standardized response mean range of 1.07-1.41 were obtained for V-RQOL. It seems that the Persian version of V-RQOL is valid, reliable, and responsive to change, and this questionnaire can be used for completing voice evaluation for patients with dysphonia. PMID:25008375

  20. 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

  1. 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. PMID:20034582

  2. 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

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

    PubMed

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

    2016-07-01

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

  4. 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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Carlini, David B; Makowski, Matthew

    2015-12-01

    The relationship between preferred codon use (PCU), developmental mode, and gene ontology (GO) was investigated in a sample of nine insect species with sequenced genomes. These species were selected to represent two distinct modes of insect development, holometabolism and hemimetabolism, with an aim toward determining whether the differences in developmental timing concomitant with developmental mode would be mirrored by differences in PCU in their developmental genes. We hypothesized that the developmental genes of holometabolous insects should be under greater selective pressure for efficient translation, manifest as increased PCU, than those of hemimetabolous insects because holometabolism requires abundant protein expression over shorter time intervals than hemimetabolism, where proteins are required more uniformly in time. Preferred codon sets were defined for each species, from which the frequency of PCU for each gene was obtained. Although there were substantial differences in the genomic base composition of holometabolous and hemimetabolous insects, both groups exhibited a general preference for GC-ending codons, with the former group having higher PCU averaged across all genes. For each species, the biological process GO term for each gene was assigned that of its Drosophila homolog(s), and PCU was calculated for each GO term category. The top two GO term categories for PCU enrichment in the holometabolous insects were anatomical structure development and cell differentiation. The increased PCU in the developmental genes of holometabolous insects may reflect a general strategy to maximize the protein production of genes expressed in bursts over short time periods, e.g., heat shock proteins. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 686-698, 2015. © 2015 Wiley Periodicals, Inc. PMID:26498580

  7. Synthetic approach to stop-codon scanning mutagenesis.

    PubMed

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

    2011-04-27

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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