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Sample records for relative codon adaptation

  1. Codon Adaptation of Plastid Genes

    PubMed Central

    Suzuki, Haruo; Morton, Brian R.

    2016-01-01

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

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

    PubMed

    Xia, Xuhua

    2015-02-01

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

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

    PubMed Central

    Wang, Hongju; Liu, Siqing; Zhang, Bo

    2016-01-01

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

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

    PubMed Central

    2012-01-01

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

  5. 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.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-10-01

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

  8. 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

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

    PubMed Central

    Zhao, Yang; Ren, Ji-Long; Wang, Ming-Yang; Zhang, Sheng-Ting; Liu, Yu; Li, Min; Cao, Yi-Bin; Zu, Hu-Yue; Chen, Xiao-Cheng; Wu, Chung-I; Nevo, Eviatar; Chen, Xue-Qun; Du, Ji-Zeng

    2013-01-01

    Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau. PMID:24297887

  10. 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.

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

    PubMed

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

    2013-11-01

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

  12. 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

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

    PubMed

    Singh, Niraj K; Tyagi, Anuj

    2017-03-21

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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2014-01-01

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

  17. 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

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

    PubMed

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

    2015-05-26

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

  19. Codon optimization underpins generalist parasitism in fungi

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Chater, Keith F; Chandra, Govind

    2008-02-01

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

  2. What drives codon choices in human genes?

    PubMed

    Karlin, S; Mrázek, J

    1996-10-04

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

  3. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-26

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

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2009-10-01

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

  13. 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

  14. Codon reassignment and amino acid composition in hemichordate mitochondria

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

    2011-01-01

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

  16. 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.

  17. 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.

  18. 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

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

    PubMed

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

    2015-01-01

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

  20. 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

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

    PubMed

    Massey, Steven E

    2017-03-27

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

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

    PubMed Central

    2011-01-01

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

  3. Age-related forgetting in locomotor adaptation.

    PubMed

    Malone, Laura A; Bastian, Amy J

    2016-02-01

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

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

    PubMed Central

    Moore, Gregory L.; Maranas, Costas D.

    2002-01-01

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

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

    PubMed

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

    2010-06-01

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

  6. Divergence in codon usage of Lactobacillus species.

    PubMed Central

    Pouwels, P H; Leunissen, J A

    1994-01-01

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

  7. 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.

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

    PubMed

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

    2016-09-23

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

  9. Principles of start codon recognition in eukaryotic translation initiation

    PubMed Central

    Lind, Christoffer; Åqvist, Johan

    2016-01-01

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

  10. Properties and determinants of codon decoding time distributions

    PubMed Central

    2014-01-01

    Background Codon decoding time is a fundamental property of mRNA translation believed to affect the abundance, function, and properties of proteins. Recently, a novel experimental technology--ribosome profiling--was developed to measure the density, and thus the speed, of ribosomes at codon resolution. Specifically, this method is based on next-generation sequencing, which theoretically can provide footprint counts that correspond to the probability of observing a ribosome in this position for each nucleotide in each transcript. Results In this study, we report for the first time various novel properties of the distribution of codon footprint counts in five organisms, based on large-scale analysis of ribosomal profiling data. We show that codons have distinctive footprint count distributions. These tend to be preserved along the inner part of the ORF, but differ at the 5' and 3' ends of the ORF, suggesting that the translation-elongation stage actually includes three biophysical sub-steps. In addition, we study various basic properties of the codon footprint count distributions and show that some of them correlate with the abundance of the tRNA molecule types recognizing them. Conclusions Our approach emphasizes the advantages of analyzing ribosome profiling and similar types of data via a comparative genomic codon-distribution-centric view. Thus, our methods can be used in future studies related to translation and even transcription elongation. PMID:25572668

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

    PubMed

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

    2016-09-02

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

  12. 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.

  13. 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

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

    PubMed Central

    Wolf, Andrew S.; Grayhack, Elizabeth J.

    2015-01-01

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

  15. Preschooler Sleep Patterns Related to Cognitive and Adaptive Functioning

    ERIC Educational Resources Information Center

    Keefe-Cooperman, Kathleen; Brady-Amoon, Peggy

    2014-01-01

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

  16. 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…

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

    PubMed Central

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

    2016-01-01

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

  18. Role of premature stop codons in bacterial evolution.

    PubMed

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

    2008-10-01

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

  19. Codon Preference Optimization Increases Prokaryotic Cystatin C Expression

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Huang, Yuan; Chen, Zhonge

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Zhang, Zhicheng; Dai, Wei; Dai, Dingzhen

    2013-01-01

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

  3. 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

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

    PubMed

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

    2016-10-12

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

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

    PubMed Central

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

    2016-01-01

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

  6. Universal response-adaptation relation in bacterial chemotaxis.

    PubMed

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

    2015-01-01

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

  7. 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.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Nissley, Daniel A; O'Brien, Edward P

    2014-12-31

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Codon Constraints on Closed 2D Shapes,

    DTIC Science & Technology

    2014-09-26

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

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

    PubMed Central

    Yap, Von Bing; Huttley, Gavin A.

    2017-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Evolutionary Dynamics of Abundant Stop Codon Readthrough

    PubMed Central

    Jungreis, Irwin; Kellis, Manolis

    2016-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Nayak, Kinshuk Chandra

    2013-01-15

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

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

    PubMed Central

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

    1994-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Lande, Russell

    2007-08-01

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

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

    PubMed Central

    Santos, M A; Tuite, M F

    1995-01-01

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

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

    PubMed

    Jiang, Peng; Sun, Xiao; Lu, Zuhong

    2007-03-01

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

  5. 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

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

    PubMed

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

    2011-03-01

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

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

    PubMed

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

    2003-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

    Rima, Bert K

    2015-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. 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.…

  13. 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…

  14. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-03-25

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

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

    PubMed

    Seligmann, Hervé

    2015-12-21

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

    Deb, Sushanta; Basak, Surajit

    2016-01-01

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

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

    PubMed

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

    2016-11-21

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

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

    NASA Astrophysics Data System (ADS)

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

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

  4. Stop codon reassignments in the wild.

    PubMed

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

    2014-05-23

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

  5. 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

  6. 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.

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

    PubMed

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

    2011-10-01

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

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

    PubMed

    Mauro, Vincent P; Chappell, Stephen A

    2014-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Telfer, Brian A.

    1994-07-01

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

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

    PubMed

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

    2015-05-01

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

  11. 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

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

    PubMed

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

    2015-01-01

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

  13. 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

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

    PubMed Central

    Chartier, Matthieu; Gaudreault, Francis; Najmanovich, Rafael

    2012-01-01

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

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

    PubMed Central

    Ahn, Insung; Bae, Se-Eun

    2011-01-01

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

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

    PubMed

    Dass, J Febin Prabhu; Sudandiradoss, C

    2012-07-15

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

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

    PubMed

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

    2017-03-20

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

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

    NASA Astrophysics Data System (ADS)

    Choptuik, M. W.

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

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

    PubMed

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

    2003-06-27

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

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

    PubMed

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

    2010-03-01

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

  1. 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.

  2. 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

  3. 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

  4. 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

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

    PubMed

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

    2005-02-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2007-01-01

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

  8. 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

  9. 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.

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

    PubMed

    Rudorf, Sophia; Lipowsky, Reinhard

    2015-01-01

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

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

    PubMed

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

    2008-01-01

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

  12. Structural basis for stop codon recognition in eukaryotes.

    PubMed

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

    2015-08-27

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

  13. 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

  14. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Qi, C; Liang, D; Jiang, X

    2001-03-01

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

  17. Efficient translation initiation dictates codon usage at gene start

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-10-28

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

  19. 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

  20. 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.

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

    PubMed

    Sueoka, N; Kawanishi, Y

    2000-12-30

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

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

    PubMed

    Rowe, G W; Trainor, L E

    1983-03-21

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

  3. 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...

  4. 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…

  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. 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…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Kenny, Maureen E.; Bledsoe, Meredith

    2005-01-01

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

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

    ERIC Educational Resources Information Center

    Roessger, Kevin M.

    2014-01-01

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

  10. 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…

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

    PubMed

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

    2008-09-01

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

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

    PubMed

    Kollmar, Martin; Mühlhausen, Stefanie

    2017-03-04

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

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

    PubMed

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

    2016-02-22

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

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

    PubMed

    Lujan, Josefina

    2008-07-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed

    Behura, Susanta K; Severson, David W

    2014-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. 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…

  20. 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…

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

    PubMed

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

    2016-01-01

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

  2. 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.

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

    PubMed

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

    1993-11-01

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

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

    PubMed

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

    2014-01-01

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

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2004-05-01

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

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

    PubMed

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

    2017-03-17

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

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

    PubMed

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

    2014-06-01

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

  13. 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

  14. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise

    PubMed Central

    Jørgensen, Sebastian B; Richter, Erik A; Wojtaszewski, Jørgen F P

    2006-01-01

    The 5′-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We furthermore discuss the possible role of AMPK as a master switch in skeletal muscle metabolism with the main focus on AMPK in metabolic regulation during muscle work. Finally, AMPK has a well established role in regulating expression of genes encoding various enzymes in muscle, and this issue is discussed in relation to adaptation of skeletal muscle to exercise training. PMID:16690705

  15. 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.

  16. 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.

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

    PubMed Central

    Asano, Katsura

    2014-01-01

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

  18. Aeromonas phages encode tRNAs for their overused codons.

    PubMed

    Prabhakaran, Ramanandan; Chithambaram, Shivapriya; Xia, Xuhua

    2014-01-01

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

  19. 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.

  20. 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

  1. 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.

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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…

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

    PubMed

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

    2011-12-01

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

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

    PubMed Central

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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

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

    PubMed

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

    2014-03-06

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

  16. 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.

  17. 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

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

    PubMed Central

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

    2004-01-01

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

  19. 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

  20. 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

  1. 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.

  2. Vulnerability and adaptation to climate-related fire impacts in rural and urban interior Alaska

    USGS Publications Warehouse

    Trainor, Sarah F.; Calef, Monika; Natcher, David; Chapin, F. Stuart; McGuire, Anthony; Huntington, Orville; Duffy, Paul A; Rupp, T. Scott; DeWilde, La'Ona; Kwart, Mary; Fresco, Nancy; Lovecraft, Amy Lauren

    2009-01-01

    This paper explores whether fundamental differences exist between urban and rural vulnerability to climate-induced changes in the fire regime of interior Alaska. We further examine how communities and fire managers have responded to these changes and what additional adaptations could be put in place. We engage a variety of social science methods, including demographic analysis, semi-structured interviews, surveys, workshops and observations of public meetings. This work is part of an interdisciplinary study of feedback and interactions between climate, vegetation, fire and human components of the Boreal forest social–ecological system of interior Alaska. We have learned that although urban and rural communities in interior Alaska face similar increased exposure to wildfire as a result of climate change, important differences exist in their sensitivity to these biophysical, climate-induced changes. In particular, reliance on wild foods, delayed suppression response, financial resources and institutional connections vary between urban and rural communities. These differences depend largely on social, economic and institutional factors, and are not necessarily related to biophysical climate impacts per se. Fire management and suppression action motivated by political, economic or other pressures can serve as unintentional or indirect adaptation to climate change. However, this indirect response alone may not sufficiently reduce vulnerability to a changing fire regime. More deliberate and strategic responses may be required, given the magnitude of the expected climate change and the likelihood of an intensification of the fire regime in interior Alaska.

  3. Adaptive evolution of foraging-related traits in a predator-prey community.

    PubMed

    Zu, Jian; Mimura, Masayasu; Takeuchi, Yasuhiro

    2011-01-07

    In this paper, with the method of adaptive dynamics and geometric technique, we investigate the adaptive evolution of foraging-related phenotypic traits in a predator-prey community with trade-off structure. Specialization on one prey type is assumed to go at the expense of specialization on another. First, we identify the ecological and evolutionary conditions that allow for evolutionary branching in predator phenotype. Generally, if there is a small switching cost near the singular strategy, then this singular strategy is an evolutionary branching point, in which predator population will change from monomorphism to dimorphism. Second, we find that if the trade-off curve is globally convex, predator population eventually branches into two extreme specialists, each completely specializing on a particular prey species. However, if the trade-off curve is concave-convex-concave, after branching in predator phenotype, the two predator species will evolve to an evolutionarily stable dimorphism at which they can continue to coexist. The analysis reveals that an attractive dimorphism will always be evolutionarily stable and that no further branching is possible under this model.

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

    PubMed

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

    2015-02-01

    Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source population climate. Common gardens were established at two intermountain west sites with progeny from two maternal parents from each of 130 wild populations. Data were collected over 2 years at each site on fifteen plant traits associated with production, phenology, and morphology. Analyses of variance revealed strong population differences for all plant traits (P < 0.0001), indicating genetic variation. Both the canonical correlation and linear correlation established associations between source populations and climate variability. Populations from warmer, more arid climates had generally lower dry weight, earlier phenology, and smaller, narrower leaves than those from cooler, moister climates. The first three canonical variates were regressed with climate variables resulting in significant models (P < 0.0001) used to map 12 seed zones. Of the 700 981 km(2) mapped, four seed zones represented 92% of the area in typically semi-arid and arid regions. The association of genetic variation with source climates in the intermountain west suggested climate driven natural selection and evolution. We recommend seed transfer zones and population movement guidelines to enhance adaptation and diversity for large-scale restoration projects.

  5. 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

  6. 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

  7. 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

  8. 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…

  9. Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

    NASA Astrophysics Data System (ADS)

    Qiao, Qin; Wang, Qia; Han, Xi; Guan, Yanlong; Sun, Hang; Zhong, Yang; Huang, Jinling; Zhang, Ticao

    2016-02-01

    The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants.

  10. 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

  11. 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

  12. 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.

  13. THE RELATION OF ENZYMATIC ADAPTATION TO THE METABOLISM OF ENDOGENOUS AND EXOGENOUS SUBSTRATES

    PubMed Central

    Spiegelman, S.; Reiner, John M.; Cohnberg, Rosellen

    1947-01-01

    The source of energy for enzymatic adaptation has been investigated. Aerobically, it is found that the endogenous carbohydrate reserves may be used as such a source. In cells depleted of their reserves, the adaptive substrate itself can be oxidized even while it cannot be fermented, and so can serve as a source of energy for the adaptation to a fermentative mode of utilization. Anaerobically, adaptation may occur at the expense of stored energy-rich compounds, while the reserves and the adaptive substrate are now useless as fuel. Such compounds appear to be more plentiful in young than in old cells. The addition of any fermentable substrate, such as glucose, leads to rapid anaerobic adaptation. Experiments in which maltose-adapted cells are adapted anaerobically to galactose with the aid of a little added maltose, and conversely, show that fermentability is the criterion of usefulness for an exogenous substrate in aiding the adaptive process. None of the endogenous and exogenous energy sources which have been investigated will facilitate adaptation unless the adaptive substrate is present while they are being consumed. The significance of these findings and the adequacy of "activation" hypotheses to explain enzymatic adaptation has been discussed. PMID:19873518

  14. 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…

  15. High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene.

    PubMed

    Sills, R C; Hong, H L; Melnick, R L; Boorman, G A; Devereux, T R

    1999-04-01

    Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras proto-oncogenes in chloroprene-induced lung and HG neoplasms. K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82). Both K- and H-ras codon 61 A-->T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A-->T transversion at K-ras codon 61. This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A-->T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A-->T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A-->T transversion at K-ras codon 61. This differed from 1,3-butadiene, where K-ras codon 13 G-->C transitions and H-ras codon 61 A-->G transitions were the predominant mutations. The major finding of K-ras A-->T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens.

  16. 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…

  17. Adaptive relative pose control for autonomous spacecraft rendezvous and proximity operations with thrust misalignment and model uncertainties

    NASA Astrophysics Data System (ADS)

    Sun, Liang; Zheng, Zewei

    2017-04-01

    An adaptive relative pose control strategy is proposed for a pursue spacecraft in proximity operations on a tumbling target. Relative position vector between two spacecraft is required to direct towards the docking port of the target while the attitude of them must be synchronized. With considering the thrust misalignment of pursuer, an integrated controller for relative translational and relative rotational dynamics is developed by using norm-wise adaptive estimations. Parametric uncertainties, unknown coupled dynamics, and bounded external disturbances are compensated online by adaptive update laws. It is proved via Lyapunov stability theory that the tracking errors of relative pose converge to zero asymptotically. Numerical simulations including six degrees-of-freedom rigid body dynamics are performed to demonstrate the effectiveness of the proposed controller.

  18. Compromised respiratory adaptation and thermoregulation in aging and age-related diseases.

    PubMed

    Chan, Sic L; Wei, Zelan; Chigurupati, Srinivasulu; Tu, Weihong

    2010-01-01

    Mitochondrial dysfunction and reactive oxygen species (ROS) production are at the heart of the aging process and are thought to underpin age-related diseases. Mitochondria are not only the primary energy-generating system but also the dominant cellular source of metabolically derived ROS. Recent studies unravel the existence of mechanisms that serve to modulate the balance between energy metabolism and ROS production. Among these is the regulation of proton conductance across the inner mitochondrial membrane that affects the efficiency of respiration and heat production. The field of mitochondrial respiration research has provided important insight into the role of altered energy balance in obesity and diabetes. The notion that respiration and oxidative capacity are mechanistically linked is making significant headway into the field of aging and age-related diseases. Here we review the regulation of cellular energy and ROS balance in biological systems and survey some of the recent relevant studies that suggest that respiratory adaptation and thermodynamics are important in aging and age-related diseases.

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

    PubMed

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

    2014-11-04

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

  20. Effect of replication on the third base of codons

    NASA Astrophysics Data System (ADS)

    Cebrat, S.; Dudek, M. R.; Gierlik, A.; Kowalczuk, M.; Mackiewicz, P.

    We have analyzed third position in codons and have observed strong long-range correlations along DNA sequence. We have shown that the correlations are caused mostly by asymmetric replication. In the analysis, we have used a DNA walk (spider analysis Cebrat et al., Microbial Comparative Genomics 2(4) (1997) 259-268) in two-dimensional space [A-T,G-C]. The particular case of the E.coli sequence has been studied in detail.

  1. Synonymous codon usage pattern in mitochondrial CYB gene in pisces, aves, and mammals.

    PubMed

    Uddin, Arif; Chakraborty, Supriyo

    2017-03-01

    Cytochrome b (CYB) protein plays an important role in complex III of the mitochondrial oxidative phosphorylation. Codon usage is the phenomenon of non-uniform usage of synonymous codons. In the present study, we report the pattern of codon usage in MT-CYB gene using various codon usage parameters. Nucleotide composition such as % of C and T was higher than A and G in pisces. In aves, % of A and C was higher than T and G but in mammals, A and T was higher than C and G. Heat map shows that AT-ending codons were mostly negative and GC-ending codons were mostly positive. From the heat map based on RSCU values, it is evident that codon usage prefers A/C at the third codon position and it was less towards T/G in its third codon position. The codons absent in pisces were AGT (except Toxotes chatareus), TGT, and CAG (except Elasma zonatum). The codons such as AGT (except Falco peregrinus), CGT (except Vidua chalybeata), and ACG (except Aythya americana) were absent in aves whereas, in mammals, the absent codons were namely CAG (except Canis familiaris) and ACG (except Rattus norvegicus). Codon usage bias was low in pisces, aves, and mammals. The frequency of leucine was the highest in the amino acid and cysteine was the lowest. Correlation analysis further suggests that mutation pressure is mainly responsible for codon usage pattern. Natural selection might also play a vital role in codon usage pattern but it was weaker than mutation pressure.

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

    PubMed Central

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

    2016-01-01

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

  3. Codon Distribution in Error-Detecting Circular Codes.

    PubMed

    Fimmel, Elena; Strüngmann, Lutz

    2016-03-15

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

  4. Inducible suppression of global translation by overuse of rare codons.

    PubMed

    Kobayashi, Hideki

    2015-04-01

    Recently, artificial gene networks have been developed in synthetic biology to control gene expression and make organisms as controllable as robots. Here, I present an artificial posttranslational gene-silencing system based on the codon usage bias and low tRNA content corresponding to minor codons. I engineered the green fluorescent protein (GFP) gene to inhibit translation indirectly with the lowest-usage codons to monopolize various minor tRNAs (lgfp). The expression of lgfp interfered nonspecifically with the growth of Escherichia coli, Saccharomyces cerevisiae, human HeLa cervical cancer cells, MCF7 breast cancer cells, and HEK293 kidney cells, as well as phage and adenovirus expansion. Furthermore, insertion of lgfp downstream of a phage response promoter conferred phage resistance on E. coli. Such engineered gene silencers could act as components of biological networks capable of functioning with suitable promoters in E. coli, S. cerevisiae, and human cells to control gene expression. The results presented here show general suppressor artificial genes for live cells and viruses. This robust system provides a gene expression or cell growth control device for artificially synthesized gene networks.

  5. 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

  6. A Synthetic Approach to Stop-Codon Scanning Mutagenesis

    PubMed Central

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

    2011-01-01

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

  7. Age-related differences in pelvic and trunk motion and gait adaptability at different walking speeds.

    PubMed

    Gimmon, Yoav; Riemer, Raziel; Rashed, Hisham; Shapiro, Amir; Debi, Ronen; Kurz, Ilan; Melzer, Itshak

    2015-10-01

    This study aimed at investigating age-related changes in gait kinematics and in kinematic adaptations over a wide range of walking velocities. Thirty-four older adults and 14 younger adults walked on a treadmill; the treadmill velocity was gradually increased in increments of 0.2miles/hour (mph) (1.1-1.9mph) and then decreased in the same increments. Pelvic, trunk, upper limbs and lower limbs angular total ranges of motion (tROM), stride time, stride length, and step width were measured. The older adults had lower pelvic, trunk tROM and shorter strides and stride time compared with the younger adults. As the treadmill speed was gradually increased, the older adults showed an inability to change the pelvic list angular motions (3.1±1.3° to 3.2±1.4°) between different walking velocities, while the younger adults showed changes (5.1±1.8° to 6.3±1.7°) as a function of the walking velocity. As the walking velocity increased, the older adults increased their stride length (from 57.0±10cm to 90.2±0.1cm) yet stride times remained constant (from 1.17±0.3sec to 1.08±0.1sec), while the younger adults increased stride length and reduced stride times (from 71.4±10cm to 103.0±7.9m and from 1.45±0.2sec to 1.22±0.1sec, respectively). In conclusion, the older adults were unable to make adaptations in pelvic and trunk kinematics between different walking speeds (rigid behavior), while the younger adults showed more flexible behavior. Pelvic and trunk kinematics in different walking speeds can be used as variables in the assessment of gait in older adults.

  8. Global Adaptation to a Lipid Environment Triggers the Dormancy-Related Phenotype of Mycobacterium tuberculosis

    PubMed Central

    Rodríguez, Juan G.; Hernández, Adriana C.; Helguera-Repetto, Cecilia; Aguilar Ayala, Diana; Guadarrama-Medina, Rosalina; Anzóla, Juan M.; Bustos, Jose R.; Zambrano, María M.; González-y-Merchand, Jorge

    2014-01-01

    ABSTRACT Strong evidence supports the idea that fatty acids rather than carbohydrates are the main energy source of Mycobacterium tuberculosis during infection and latency. Despite that important role, a complete scenario of the bacterium’s metabolism when lipids are the main energy source is still lacking. Here we report the development of an in vitro model to analyze adaptation of M. tuberculosis during assimilation of long-chain fatty acids as sole carbon sources. The global lipid transcriptome revealed a shift toward the glyoxylate cycle, the overexpression of main regulators whiB3, dosR, and Rv0081, and the increased expression of several genes related to reductive stress. Our evidence showed that lipid storage seems to be the selected mechanism used by M. tuberculosis to ameliorate the assumed damage of reductive stress and that concomitantly the bacilli acquired a slowed-growth and drug-tolerant phenotype, all characteristics previously associated with the dormant stage. Additionally, intergenic regions were also detected, including the unexpected upregulation of tRNAs that suggest a new role for these molecules in the acquisition of a drug-tolerant phenotype by dormant bacilli. Finally, a set of lipid signature genes for the adaptation process was also identified. This in vitro model represents a suitable condition to illustrate the participation of reductive stress in drugs’ activity against dormant bacilli, an aspect scarcely investigated to date. This approach provides a new perspective to the understanding of latent infection and suggests the participation of previously undetected molecules. PMID:24846381

  9. Codon usage in mammalian genes is biased by sequence slippage mechanisms.

    PubMed

    Bains, W

    1993-01-01

    The codons for some conserved amino acids are found to be the same between homologous genes from different species when the statistics of codon usage would suggest that they should be different. I examine whether this 'coincidence' of codon usage could be due to genetic mechanisms homogenising the DNA around specific sites. This paper describes the further analysis of the coincident codons in 19 genes (a total of 96 homologues) for slippage. Coincident codons arise in contexts of increased sequence simplicity, and have a high chance of occurring within sequences similar to the recombination-prone minisatellite 'core' sequence. This suggests a role of genetic homogenisation in their generation.

  10. 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.

  11. Experimental demonstration of single-mode fiber coupling over relatively strong turbulence with adaptive optics.

    PubMed

    Chen, Mo; Liu, Chao; Xian, Hao

    2015-10-10

    High-speed free-space optical communication systems using fiber-optic components can greatly improve the stability of the system and simplify the structure. However, propagation through atmospheric turbulence degrades the spatial coherence of the signal beam and limits the single-mode fiber (SMF) coupling efficiency. In this paper, we analyze the influence of the atmospheric turbulence on the SMF coupling efficiency over various turbulences. The results show that the SMF coupling efficiency drops from 81% without phase distortion to 10% when phase root mean square value equals 0.3λ. The simulations of SMF coupling with adaptive optics (AO) indicate that it is inevitable to compensate the high-order aberrations for SMF coupling over relatively strong turbulence. The SMF coupling efficiency experiments, using an AO system with a 137-element deformable mirror and a Hartmann-Shack wavefront sensor, obtain average coupling efficiency increasing from 1.3% in open loop to 46.1% in closed loop under a relatively strong turbulence, D/r0=15.1.

  12. Adaptive and maladaptive components of rumination? Diagnostic specificity and relation to depressive biases.

    PubMed

    Joormann, Jutta; Dkane, Marco; Gotlib, Ian H

    2006-09-01

    The present study investigated the validity of the two-factor solution of items selected from the Rumination Scale of the Response Style Questionnaire proposed by Treynor, Gonzalez, and Nolen-Hoeksema (2003). In the first part of this study we used samples of currently depressed (MDD), formerly depressed (FD), socially anxious (SP), and healthy control participants to examine whether the brooding and reflective pondering components differentiate participants with an anxiety disorder from participants with depression. In the second part of this study we examined whether these components of rumination were differentially related to cognitive biases in depression. Overall, the MDD group exhibited higher brooding scores than did all other groups; SP and FD groups did not differ from each other but obtained higher brooding scores than did the control participants. Only the MDD and the control groups differed on the reflective pondering factor. Importantly, brooding and reflective pondering were differentially related to cognitive biases. Specifically, the correlation between brooding/reflective pondering and memory bias was not significant when depressive symptoms were partialed out. The correlation between brooding and attentional bias for sad faces, however, remained significant even when current depressive symptoms were taken into account. In sum, our results support the formulation that rumination is composed of an adaptive reflective pondering factor and a maladaptive brooding factor.

  13. Nucleotide diversity patterns of local adaptation at drought-related candidate genes in wild tomatoes.

    PubMed

    Xia, Hui; Camus-Kulandaivelu, Létizia; Stephan, Wolfgang; Tellier, Aurélien; Zhang, Zhenwen

    2010-10-01

    We surveyed nucleotide diversity at two candidate genes LeNCED1 and pLC30-15, involved in an ABA (abscisic acid) signalling pathway, in two closely related tomato species Solanum peruvianum and Solanum chilense. Our six population samples (three for each species) cover a range of mesic to very dry habitats. The ABA pathway plays an important role in the plants' response to drought stress. LeNCED1 is an upstream gene involved in ABA biosynthesis, and pLC30-15 is a dehydrin gene positioned downstream in the pathway. The two genes show very different patterns of nucleotide variation. LeNCED1 exhibits very low nucleotide diversity relative to the eight neutral reference loci that were previously surveyed in these populations. This suggests that strong purifying selection has been acting on this gene. In contrast, pLC30-15 exhibits higher levels of nucleotide diversity and, in particular in S. chilense, higher genetic differentiation between populations than the reference loci, which is indicative of local adaptation. In the more drought-tolerant species S. chilense, one population (from Quicacha) shows a significant haplotype structure, which appears to be the result of positive (diversifying) selection.

  14. 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

  15. Putative mitochondrial polypeptides coded by expanded quadruplet codons, decoded by antisense tRNAs with unusual anticodons.

    PubMed

    Seligmann, Hervé

    2012-11-01

    Weak triplet codon-anticodon interactions render ribosome-free translation unlikely. Some modern tRNAs read quadruplet codons (tetracodons), suggesting vestigial ribosome-free translation. Here, mitochondrial genomes are explored for tetracoded overlapping protein coding (tetra)genes. Occasional single tetracodons within regular mitochondrial genes coevolve positively/negatively with antisense tRNAs with predicted reduced/expanded anticodons (depending on taxon), suggesting complex tetra-decoding mechanisms. Transcripts of antisense tRNAs with unusual anticodons are more abundant than of homologues with regular anticodons. Assuming overlapping tetracoding with silent 4th tetracodon position, BLAST aligns 10 putative tetragenes spanning 17% of regular human mitochondrial protein coding tricodons with 14 GenBank proteins. Various tests including predicted peptide secondary structures, 3rd codon position (of the regular main frame of the protein coding gene) conservation against replicational deamination mutation gradients, and circular code usage (overlapping genes avoid using circular code codons) confirm tetracoding in these overlapping tetragenes with silent 4th position, but not for BLAST-predicted tetragenes assuming silent 2nd or 3rd positions. This converges with tetradecoding mechanisms that are more compatible with silent 4th, than at other, tetracodon positions. Tetracoding increases with (a) GC-contents, perhaps conserved or switched on in high temperature conditions; (b) usage of theoretically predicted 'tessera' tetracodons; (c) 12s rRNA stability; and d) antisense tRNA numbers with predicted expanded anticodons. Most detected tetragenes are not evolutionarily conserved, apparently reflect specific, transient adaptations. Tetracoding increases with mammal longevity.

  16. 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.

  17. 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

  18. The Relation between Intellectual Functioning and Adaptive Behavior in the Diagnosis of Intellectual Disability

    ERIC Educational Resources Information Center

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

    2016-01-01

    Intellectual disability originates during the developmental period and is characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. In this article, we present a brief history of the diagnostic criteria of intellectual disability for both…

  19. Evaluation of the field-adapted ADMA approach: absolute and relative energies of crambin and derivatives.

    PubMed

    Exner, Thomas E; Mezey, Paul G

    2005-12-21

    A large number of conformations and chemically modified variants of the protein crambin were used to extensively test the field-adapted adjustable density matrix assembler (FA-ADMA) method developed for ab initio quality quantum chemistry computations of proteins and other macromolecules, introduced in an earlier publication. In this method, the fuzzy density matrix fragmentation scheme of the original adjustable density matrix assembler (ADMA) method has been made more efficient by combining it with an approach of using point charges to approximate the effects of additional, distant parts of a given macromolecule in the quantum chemical calculation of each fragment. In this way, smaller parent molecules can be used for fragment generation, while achieving accuracy that can be obtained only with large parent molecules in the original ADMA method. Whereas in both methods the error relative to the Hartree-Fock result can be reduced below any threshold by choosing large enough parent molecules, this can be done more efficiently with the new method. In order to obtain reliable test results for the accuracy obtainable by the new method when compared to conventional Hartree-Fock calculations, we performed a large number of energy calculations for the protein crambin using various conformations available in the Protein Data Bank, various protonation states, and side chain mutations. Additionally, in order to test the performance of the method for protein-solvent interaction studies, the energy changes due to the formation of complexes with ethanol and single and multiple water molecules were investigated.

  20. Adapting to changing memory retrieval demands: evidence from event-related potentials.

    PubMed

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

    2009-06-01

    This study investigated preparatory processes involved in adapting to changing episodic memory retrieval demands. Event-related potentials (ERPs) were recorded while participants performed a general old/new recognition task and a specific task that also required retrieval of perceptual details. The relevant task remained either constant or changed (predictably or randomly) across trials. Responses were slowed when participants switched from the specific to the general task but not vice versa. Hence, asymmetrical switch costs were observed, suggesting that retrieval preparation is dependent not only on the current retrieval goal but also influenced by recent retrieval attempts. Consistently, over posterior scalp regions ERPs associated with advance preparation were modulated by the preceding task, reflecting increased attentional selection requirements for the general task, and by the foreknowledge about the task sequence. When retrieval demands remained constant, frontal slow-waves elicited by retrieval-cues were more positive going for the specific task, indicating full implementation of a retrieval orientation that allows more efficient retrieval of perceptual details.

  1. 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

  2. Adaptation of hybrid human-computer interaction systems using EEG error-related potentials.

    PubMed

    Chavarriaga, Ricardo; Biasiucci, Andrea; Forster, Killian; Roggen, Daniel; Troster, Gerhard; Millan, Jose Del R

    2010-01-01

    Performance improvement in both humans and artificial systems strongly relies in the ability of recognizing erroneous behavior or decisions. This paper, that builds upon previous studies on EEG error-related signals, presents a hybrid approach for human computer interaction that uses human gestures to send commands to a computer and exploits brain activity to provide implicit feedback about the recognition of such commands. Using a simple computer game as a case study, we show that EEG activity evoked by erroneous gesture recognition can be classified in single trials above random levels. Automatic artifact rejection techniques are used, taking into account that subjects are allowed to move during the experiment. Moreover, we present a simple adaptation mechanism that uses the EEG signal to label newly acquired samples and can be used to re-calibrate the gesture recognition system in a supervised manner. Offline analysis show that, although the achieved EEG decoding accuracy is far from being perfect, these signals convey sufficient information to significantly improve the overall system performance.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Electrophoresis and spectrometric analyses of adaptation-related proteins in thermally stressed Chromobacterium violaceum.

    PubMed

    Cordeiro, I B; Castro, D P; Nogueira, P P O; Angelo, P C S; Nogueira, P A; Gonçalves, J F C; Pereira, A M R F; Garcia, J S; Souza, G H M F; Arruda, M A Z; Eberlin, M N; Astolfi-Filho, S; Andrade, E V; López-Lozano, J L

    2013-10-29

    Chromobacterium violaceum is a Gram-negative proteobacteria found in water and soil; it is widely distributed in tropical and subtropical regions, such as the Amazon rainforest. We examined protein expression changes that occur in C. violaceum at different growth temperatures using electrophoresis and mass spectrometry. The total number of spots detected was 1985; the number ranged from 99 to 380 in each assay. The proteins that were identified spectrometrically were categorized as chaperones, proteins expressed exclusively under heat stress, enzymes involved in the respiratory and fermentation cycles, ribosomal proteins, and proteins related to transport and secretion. Controlling inverted repeat of chaperone expression and inverted repeat DNA binding sequences, as well as regions recognized by sigma factor 32, elements involved in the genetic regulation of the bacterial stress response, were identified in the promoter regions of several of the genes coding proteins, involved in the C. violaceum stress response. We found that 30 °C is the optimal growth temperature for C. violaceum, whereas 25, 35, and 40 °C are stressful temperatures that trigger the expression of chaperones, superoxide dismutase, a probable small heat shock protein, a probable phasing, ferrichrome-iron receptor protein, elongation factor P, and an ornithine carbamoyltransferase catabolite. This information improves our comprehension of the mechanisms involved in stress adaptation by C. violaceum.

  8. Natural reassignment of CUU and CUA sense codons to alanine in Ashbya mitochondria

    PubMed Central

    Ling, Jiqiang; Daoud, Rachid; Lajoie, Marc J.; Church, George M.; Söll, Dieter; Lang, B. Franz

    2014-01-01

    The discovery of diverse codon reassignment events has demonstrated that the canonical genetic code is not universal. Studying coding reassignment at the molecular level is critical for understanding genetic code evolution, and provides clues to genetic code manipulation in synthetic biology. Here we report a novel reassignment event in the mitochondria of Ashbya (Eremothecium) gossypii, a filamentous-growing plant pathogen related to yeast (Saccharomycetaceae). Bioinformatics studies of conserved positions in mitochondrial DNA-encoded proteins suggest that CUU and CUA codons correspond to alanine in A. gossypii, instead of leucine in the standard code or threonine in yeast mitochondria. Reassignment of CUA to Ala was confirmed at the protein level by mass spectrometry. We further demonstrate that a predicted is transcribed and accurately processed in vivo, and is responsible for Ala reassignment. Enzymatic studies reveal that is efficiently recognized by A. gossypii mitochondrial alanyl-tRNA synthetase (AgAlaRS). AlaRS typically recognizes the G3:U70 base pair of tRNAAla; a G3A change in Ashbya abolishes its recognition by AgAlaRS. Conversely, an A3G mutation in Saccharomyces cerevisiae confers tRNA recognition by AgAlaRS. Our work highlights the dynamic feature of natural genetic codes in mitochondria, and the relative simplicity by which tRNA identity may be switched. PMID:24049072

  9. Likelihood models of somatic mutation and codon substitution in cancer genes.

    PubMed Central

    Yang, Ziheng; Ro, Simon; Rannala, Bruce

    2003-01-01

    The role of somatic mutation in cancer is well established and several genes have been identified that are frequent targets. This has enabled large-scale screening studies of the spectrum of somatic mutations in cancers of particular organs. Cancer gene mutation databases compile the results of many studies and can provide insight into the importance of specific amino acid sequences and functional domains in cancer, as well as elucidate aspects of the mutation process. Past studies of the spectrum of cancer mutations (in particular genes) have examined overall frequencies of mutation (at specific nucleotides) and of missense, nonsense, and silent substitution (at specific codons) both in the sequence as a whole and in a specific functional domain. Existing methods ignore features of the genetic code that allow some codons to mutate to missense, or stop, codons more readily than others (i.e., by one nucleotide change, vs. two or three). A new codon-based method to estimate the relative rate of substitution (fixation of a somatic mutation in a cancer cell lineage) of nonsense vs. missense mutations in different functional domains and in different tumor tissues is presented. Models that account for several potential influences on rates of somatic mutation and substitution in cancer progenitor cells and allow biases of mutation rates for particular dinucleotide sequences (CGs and dipyrimidines), transition vs. transversion bias, and variable rates of silent substitution across functional domains (useful in detecting investigator sampling bias) are considered. Likelihood-ratio tests are used to choose among models, using cancer gene mutation data. The method is applied to analyze published data on the spectrum of p53 mutations in cancers. A novel finding is that the ratio of the probability of nonsense to missense substitution is much lower in the DNA-binding and transactivation domains (ratios near 1) than in structural domains such as the linker, tetramerization

  10. Development of a Mediterranean diet score adapted to Japan and its relation to obesity risk

    PubMed Central

    Kanauchi, Masao; Kanauchi, Kimiko

    2016-01-01

    Background The Mediterranean diet (MD) is well known as a healthy diet that protects against several chronic diseases. However, there is no appropriate and easy index to assess adherence to the MD pattern in Japan. Objective The aim of this study was to develop a novel instrument to measure MD adherence adapted to a Japanese diet and to examine its association with overweight/obesity risk. Methods A cross-sectional nutritional survey provided the data for construction of a novel MD score. In total, 1,048 subjects who were employees and university students, aged 18–68 years (645 men and 403 women), completed a 58-item brief-type self-administered dietary history questionnaire. We constructed a Japanese-adapted MD score (jMD score) focusing on 13 components. Adherence to the jMD was categorized as low (score 0–4), moderate (5–7), or high (8–13). Results Men had higher jMD scores than women, and adherence to the jMD score increased with age. Only 11.6% of subjects showed high adherence to the jMD, whereas 29.6% showed low adherence. A higher jMD adherence was associated with a higher intake of favorable nutrients with the exception of salt. The jMD adherence was significantly associated with a reduced likelihood of having overweight/obesity for the highest category compared with lowest category (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.30–0.85, p-trend=0.017) after adjusting for age, sex, smoking, physical activity, alcohol intake, and hypertension. A two-point increment in jMD score was related to a reduced likelihood of having overweight/obesity with an odds ratio of 0.76 (95% CI 0.65–0.90, p=0.002). Conclusions Our novel jMD score confirmed reasonable associations with nutrient intakes, and higher MD adherence was associated with a lower prevalence of overweight/obesity. PMID:27806831

  11. Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation.

    PubMed

    Hu, Minyi; Cheng, Jiqi; Bethel, Neville; Serra-Hsu, Frederick; Ferreri, Suzanne; Lin, Liangjun; Qin, Yi-Xian

    2014-09-01

    Interstitial bone fluid flow (IBFF) is suggested as a communication medium that bridges external physical signals and internal cellular activities in the bone, which thus regulates bone remodeling. Intramedullary pressure (ImP) is one main regulatory factor of IBFF and bone adaptation related mechanotransduction. Our group has recently observed that dynamic hydraulic stimulation (DHS), as an external oscillatory muscle coupling, was able to induce local ImP with minimal bone strain as well as to mitigate disuse bone loss. The current study aimed to evaluate the dose dependent relationship between DHS's amplitude, i.e., 15 and 30mmHg, and in vivo ImP induction, as well as this correlation on bone's phenotypic change. Simultaneous measurements of ImP and DHS cuff pressures were obtained from rats under DHS with various magnitudes and a constant frequency of 2Hz. ImP inductions and cuff pressures upon DHS loading showed a positively proportional response over the amplitude sweep. The relationship between ImP and DHS cuff pressure was evaluated and shown to be proportional, in which ImP was raised with increases of DHS cuff pressure amplitudes (R(2)=0.98). A 4-week in vivo experiment using a rat hindlimb suspension model demonstrated that the mitigation effect of DHS on disuse trabecular bone was highly dose dependent and related to DHS's amplitude, where a higher ImP led to a higher bone volume. This study suggested that sufficient physiological DHS is needed to generate ImP. Oscillatory DHS, potentially induces local fluid flow, has shown dose dependence in attenuation of disuse osteopenia.

  12. 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

  13. Age-related changes and sex differences in postural control adaptability in children during periodic floor oscillation with eyes closed.

    PubMed

    Fujiwara, Katsuo; Kiyota, Takeo; Mammadova, Aida; Yaguchi, Chie

    2011-01-01

    We investigated age-related changes and sex differences in adaptability of anticipatory postural control in children. Subjects comprised 449 children (4-12 years old) and 109 young adults (18-29 years old). Subjects stood with eyes closed on a force-platform fixed to a floor oscillator. We conducted five trials of 1-minute oscillation (0.5 Hz frequency, 2.5 cm amplitude) in the anteroposterior direction. Postural steadiness was quantified as the mean speed of the center of pressure in the anteroposterior direction (CoPy). In young adults, CoPy speed decreased rapidly until the third trial for both sexes. Adaptability was evaluated by changes in steadiness. The adaptability of children was categorized as "good," "moderate," and "poor," compared with a standard variation of the mean CoPy speed regression line between the first and fifth trials in young adults. Results were as follows: (1) anticipatory postural control adaptability starts to develop from age 6 in boys and 5 in girls, and greatly improves at age 7-8 in boys and 6 in girls; (2) the adaptability of children at age 11-12 (74% of boys and 63% of girls were categorized as "good") has not yet reached the same level as for young adults; (3) the adaptability at age 11-12 for girls is temporarily disturbed due to early puberty.

  14. Children's enduring PTSD symptoms are related to their family's adaptability and cohesion.

    PubMed

    Birmes, Philippe; Raynaud, Jean-Philippe; Daubisse, Laetitia; Brunet, Alain; Arbus, Christophe; Klein, Rémy; Cailhol, Lionel; Allenou, Charlotte; Hazane, Franck; Grandjean, Hélène; Schmitt, Laurent

    2009-08-01

    This study compared, 18-24 months after an industrial disaster, in two groups of children (those with clinically relevant PTSD symptoms versus those with low PTSD symptoms), the child's perception of family cohesion and adaptability, the child's experience of the explosion, and parental characteristics. Enmeshed family cohesion or rigid family adaptability were more frequently found in children with low PTSD symptoms. PTSD symptoms in the mother, living in a family of 3 or more children, and being female were significantly associated with PTSD symptoms in the children. The assessment of traumatized children should include assessment of family's adaptability and cohesion.

  15. 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.

  16. Comparison of two codon optimization strategies to enhance recombinant protein production in Escherichia coli

    PubMed Central

    2011-01-01

    Background Variations in codon usage between species are one of the major causes affecting recombinant protein expression levels, with a significant impact on the economy of industrial enzyme production processes. The use of codon-optimized genes may overcome this problem. However, designing a gene for optimal expression requires choosing from a vast number of possible DNA sequences and different codon optimization methods have been used in the past decade. Here, a comparative study of the two most common methods is presented using calf prochymosin as a model. Results Seven sequences encoding calf prochymosin have been designed, two using the "one amino acid-one codon" method and five using a "codon randomization" strategy. When expressed in Escherichia coli, the variants optimized by the codon randomization approach produced significantly more proteins than the native sequence including one gene that produced an increase of 70% in the amount of prochymosin accumulated. On the other hand, no significant improvement in protein expression was observed for the variants designed with the one amino acid-one codon method. The use of codon-optimized sequences did not affect the quality of the recovered inclusion bodies. Conclusions The results obtained in this study indicate that the codon randomization method is a superior strategy for codon optimization. A significant improvement in protein expression was obtained for the largely established process of chymosin production, showing the power of this strategy to reduce production costs of industrial enzymes in microbial hosts. PMID:21371320

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

    PubMed

    Carlini, David B; Makowski, Matthew

    2015-12-01

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

  18. Evolution of Synonymous Codon Usage in the Mitogenomes of Certain Species of Bilaterian Lineage with Special Reference to Chaetognatha

    PubMed Central

    Karumathil, Sudeesh; Dirisala, Vijaya R.; Srinadh, Uthpala; Nikhil, Valaboju; Kumar, N. Satya Sampath; Nair, Rahul R.

    2016-01-01

    Chaetognatha is a minor phylum, comprising transparent marine invertebrates varying in size from 0.5 to 12 cm. The exact phylogenetic position of Chaetognatha in Metazoa has not been deciphered as some embryological characteristics place chaetognaths among deuterostomes and some morphological characteristics place these among protostomes. In this study, the major factors that drive synonymous codon usage bias (SCUB) in the mitogenomes of representative species of Chaetognatha and chosen species of other closely related phyla were analyzed. Spearman’s rank correlation analyses of nucleotide contents suggested that mutational pressure and selection were acting in all examined mitogenomes but with varying intensities. The quantification of SCUB using effective number of codons vs. GC composition at the third codon position (GC3) plot suggested that mutational pressure due to GC compositional constraints might be one of the major influencing forces driving the SCUB in all chaetognaths except Sagitta enflata. However, neutrality plots revealed no significant correlation between GC3 and cumulative GC content at first and second codon positions (GC12) in all other species, except in Daphnia pulex. The parity rule 2 bias plot showed that significant compositional differences existed between C and G, as well as between A and T, contents in most of the protein-coding genes (PCGs) and, comparatively, A and T contents were used more proportionally than C and G contents in all chosen mitogenomes. Chi-square analysis revealed the presence of putative optimal codons in all species, except in S. enflata. The correspondence analysis identified that mutational pressure and selection act on the mitogenomes of the selected chaetognaths and other phyla with varying intensities. The cluster analysis based on relative synonymous codon usage (RSCU) values revealed that RSCU variations in the PCGs of mitogenomes of chaetognaths are more comparable with those of protostomes. Apart from

  19. Investigating the Impact of Formal Reflective Activities on Skill Adaptation in a Work-Related Instrumental Learning Setting

    ERIC Educational Resources Information Center

    Roessger, Kevin M.

    2013-01-01

    In work-related, instrumental learning contexts the role of reflective activities is unclear. Kolb's (1985) experiential learning theory and Mezirow's transformative learning theory (2000) predict skill-adaptation as a possible outcome. This prediction was experimentally explored by manipulating reflective activities and assessing participants'…

  20. Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

    2005-01-01

    Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

  1. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    PubMed

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment.

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

    PubMed Central

    Terenin, Ilya M.; Akulich, Kseniya A.; Andreev, Dmitry E.; Polyanskaya, Sofya A.; Shatsky, Ivan N.; Dmitriev, Sergey E.

    2016-01-01

    During eukaryotic translation initiation, 43S ribosomal complex scans mRNA leader unless an AUG codon in an appropriate context is found. Establishing the stable codon–anticodon base-pairing traps the ribosome on the initiator codon and triggers structural rearrangements, which lead to Pi release from the eIF2-bound GTP. It is generally accepted that AUG recognition by the scanning 43S complex sets the final point in the process of start codon selection, while latter stages do not contribute to this process. Here we use translation reconstitution approach and kinetic toe-printing assay to show that after the 48S complex is formed on an AUG codon, in case GTP hydrolysis is impaired, the ribosomal subunit is capable to resume scanning and slides downstream to the next AUG. In contrast to leaky scanning, this sliding is not limited to AUGs in poor nucleotide contexts and occurs after a relatively long pause at the recognized AUG. Thus, recognition of an AUG per se does not inevitably lead to this codon being selected for initiation of protein synthesis. Instead, it is eIF5-induced GTP hydrolysis and Pi release that irreversibly trap the 48S complex, and this complex is further stabilized by eIF5B and 60S joining. PMID:26717981

  3. Age-Related, Sport-Specific Adaptions of the Shoulder Girdle in Elite Adolescent Tennis Players

    PubMed Central

    Cools, Ann M.; Palmans, Tanneke; Johansson, Fredrik R.

    2014-01-01

    Context: Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. Objective: To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (<14, 14–16, and >16 years). Design: Cross-sectional study. Setting: Tennis training sports facilities. Patients or Other Participants: Fifty-nine adolescent Swedish elite tennis players (ages 10–20 years) selected based on their national ranking. Main Outcome Measure(s): We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Results: Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight–normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Conclusions: Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence. PMID:25098662

  4. An attentional-adaptation account of spatial negative priming: evidence from event-related potentials.

    PubMed

    Liu, Xiaonan L; Walsh, Matthew M; Reder, Lynne M

    2014-03-01

    Negative priming (NP) refers to a slower response to a target stimulus if it has been previously ignored. To examine theoretical accounts of spatial NP, we recorded behavioral measures and event-related potentials (ERPs) in a target localization task. A target and distractor briefly appeared, and the participant pressed a key corresponding to the target's location. The probability of the distractor appearing in each of four locations varied, whereas the target appeared with equal probabilities in all locations. We found that response times (RTs) were fastest when the prime distractor appeared in its most probable (frequent) location and when the prime target appeared in the location that never contained a distractor. Moreover, NP effects varied as a function of location: They were smallest when targets followed distractors in the frequent distractor location-a finding not predicted by episodic-retrieval or suppression accounts of NP. The ERP results showed that the P2, an ERP component associated with attentional orientation, was smaller in prime displays when the distractor appeared in its frequent location. Moreover, no differences were apparent between negative-prime and control trials in the N2, which is associated with suppression processes, nor in the P3, which is associated with episodic retrieval processes. These results indicate that the spatial NP effect is caused by both short- and long-term adaptation in preferences based on the history of inspecting unsuccessful locations. This article is dedicated to the memory of Edward E. Smith, and we indicate how this study was inspired by his research career.

  5. Role of Calcitonin Gene-Related Peptide in Functional Adaptation of the Skeleton

    PubMed Central

    Sample, Susannah J.; Heaton, Caitlin M.; Behan, Mary; Bleedorn, Jason A.; Racette, Molly A.; Hao, Zhengling; Muir, Peter

    2014-01-01

    Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPβ. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPβ knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPβ knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation. PMID:25536054

  6. Blastocystis Mitochondrial Genomes Appear to Show Multiple Independent Gains and Losses of Start and Stop Codons

    PubMed Central

    Jacob, Alison S.; Andersen, Lee O’Brien; Bitar, Paulina Pavinski; Richards, Vincent P.; Shah, Sarah; Stanhope, Michael J.; Stensvold, C. Rune; Clark, C. Graham

    2016-01-01

    Complete mitochondrion-related organelle (MRO) genomes of several subtypes (STs) of the unicellular stramenopile Blastocystis are presented. Complete conservation of gene content and synteny in gene order is observed across all MRO genomes, comprising 27 protein coding genes, 2 ribosomal RNA genes, and 16 transfer RNA (tRNA) genes. Despite the synteny, differences in the degree of overlap between genes were observed between subtypes and also between isolates within the same subtype. Other notable features include unusual base-pairing mismatches in the predicted secondary structures of some tRNAs. Intriguingly, the rps4 gene in some MRO genomes is missing a start codon and, based on phylogenetic relationships among STs, this loss has happened twice independently. One unidentified open reading frame (orf160) is present in all MRO genomes. However, with the exception of ST4 where the feature has been lost secondarily, orf160 contains variously one or two in-frame stop codons. The overall evidence suggests that both the orf160 and rps4 genes are functional in all STs, but how they are expressed remains unclear. PMID:27811175

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

    PubMed

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

    2015-08-01

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

  8. Reduced efficacy of natural selection on codon usage bias in selfing Arabidopsis and Capsella species.

    PubMed

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

    2011-01-01

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

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

    PubMed Central

    Detanico, Thiago; Phillips, Matthew; Wysocki, Lawrence J.

    2016-01-01

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

  10. Codon-optimized Human Sodium Iodide Symporter (opt-hNIS) as a Sensitive Reporter and Efficient Therapeutic Gene

    PubMed Central

    Kim, Young-Hwa; Youn, Hyewon; Na, Juri; Hong, Kee-Jong; Kang, Keon Wook; Lee, Dong Soo; Chung, June-Key

    2015-01-01

    To generate a more efficient in vivo reporter and therapeutic gene, we optimized the coding sequence of the human sodium/iodide symporter (NIS) gene by replacing NIS DNA codons from wild type to new codons having the highest usage in human gene translation. The Codon Adaptation Index (CAI), representing the number of codons effective for human expression, was much improved (0.79 for hNIS, 0.97 for opt-hNIS). Both wild-type (hNIS) and optimized human NIS (opt-hNIS) were cloned into pcDNA3.1 and pMSCV vectors for transfection. Various cancer cell lines such as thyroid (TPC-1, FRO, B-CPAP), breast (MDA-MB-231), liver (Hep3B), cervical (HeLa), and glioma (U87MG) were transfected with pcDNA3.1/hNIS or pcDNA3.1/opt-hNIS. 125I uptake by opt-hNIS-expressing cells was 1.6 ~ 2.1 times higher than uptake by wild-type hNIS-expressing cells. Stable cell lines were also established by retroviral transduction using pMSCV/hNIS or pMSCV/opt-hNIS, revealing higher NIS protein levels and 125I uptake in opt-hNIS-expressing cells than in hNIS-expressing cells. Moreover, scintigraphic images from cell plates and mouse xenografts showed stronger signals from opt-hNIS-expressing cells than hNIS-expressing cells, and radioactivity uptake by opt-hNIS-expressing tumors was 2.3-fold greater than that by hNIS-expressing tumors. To test the efficacy of radioiodine therapy, mouse xenograft models were established with cancer cells expressing hNIS or opt-hNIS. 131I treatment reduced tumor sizes of hNIS- and opt-hNIS-expressing tumors to 0.57- and 0.27- fold, respectively, compared to their sizes before therapy, suggesting an improved therapeutic effect of opt-hNIS. In summary, this study shows that codon optimization strongly increases hNIS protein levels and radioiodine uptake, thus supporting opt-hNIS as a more sensitive reporter and efficient therapeutic gene. PMID:25553100

  11. Codon recognition during frameshift suppression in Saccharomyces cerevisiae.

    PubMed Central

    Gaber, R F; Culbertson, M R

    1984-01-01

    A genetic approach has been used to establish the molecular basis of 4-base codon recognition by frameshift suppressor tRNA containing an extra nucleotide in the anticodon. We have isolated all possible base substitution mutations at the position 4 (N) in the 3'-CCCN-5' anticodon of a Saccharomyces cerevisiae frameshift suppressor glycine tRNA encoded by the SUF16 gene. Base substitutions at +1 frameshift sites in the his4 gene have also been obtained such that all possible 4-base 5'-GGGN-3' codons have been identified. By testing for suppression in different strains that collectively represent all 16 possible combinations of position 4 nucleotides, we show that frameshift suppression does not require position 4 base pairing. Nonetheless, position 4 interactions influence the efficiency of suppression. Our results suggest a model in which 4-base translocation of mRNA on the ribosome is directed primarily by the number of nucleotides in the anticodon loop, whereas the resulting efficiency of suppression is dependent on the nature of position 4 nucleotides. Images PMID:6390183

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

    PubMed

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

    2004-01-01

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

  13. Waterloo Vision and Mobility Study: gait adaptations to altered surfaces in individuals with age-related maculopathy.

    PubMed

    Spaulding, S J; Patla, A E; Elliott, D B; Flanagan, J; Rietdyk, S; Brown, S

    1994-12-01

    Walking is an extremely complex task that can become seriously challenged if one of the sensory systems which provides input to the motor system is compromised. The present study evaluated gait adaptations to altered surface characteristics and high and low ambient light conditions by subjects with age-related maculopathy (ARM). Twenty subjects with ARM and 20 control subjects walked along a 6 m path, along which they met 1 of 3 altered surfaces (compliant, uneven, or shiny). Kinematic data and ground reaction forces information were analyzed to discern gait adaptation strategies used by the ARM group. Ten trials on each surface were collected under both high and low ambient light levels. The ARM subjects were found to be generally more cautious when walking on the altered surfaces. For example, they walked more slowly, with a longer swing time. However, gait adaptations in the ARM group were not merely scaled versions of normal gait but were adjustments to adapt to environmental changes. Gait was modified to avoid tripping over a surface edge, to prevent slipping at heel contact, and to balance during stance. These adaptations enabled subjects to maintain safe mobility when walking in a challenging environment.

  14. Age-related decline in thermal adaptation capacities: an evoked potentials study.

    PubMed

    Kemp, Jennifer; Després, Olivier; Pebayle, Thierry; Dufour, André

    2014-06-01

    Aging is associated with changes in thermosensitivity and decreases in the functionality of the autonomic thermoregulation. The underlying mechanisms are, however, not fully understood. Elderly subjects may undergo functional changes in the integration process of the thermal sensory system, especially in their thermal adaptation capacities. To verify this hypothesis, we compared thermal evoked responses in younger and older subjects exposed to thermoneutral (27 °C) and warm (30 °C) environments. In the warm environment, the amplitudes of thermal evoked potentials (EPs) were significantly lower in older than in younger subjects, whereas in the thermoneutral environment, the EP amplitudes were similar in both groups. These findings suggest that thermal adaptation capacities are reduced in elderly individuals, due to a dysfunction of C-fibers with aging, particularly expressed by lowered adaptation capacities to temperature variations.

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

    SciTech Connect

    Petraroli, R.; Pocchiari, M.

    1996-04-01

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

  16. Codon-specific and general inhibition of protein synthesis by the tRNA-sequestering minigenes.

    PubMed

    Delgado-Olivares, Luis; Zamora-Romo, Efraín; Guarneros, Gabriel; Hernandez-Sanchez, Javier

    2006-07-01

    The expression of minigenes in bacteria inhibits protein synthesis and cell growth. Presumably, the translating ribosomes, harboring the peptides as peptidyl-tRNAs, pause at the last sense codon of the minigene directed mRNAs. Eventually, the peptidyl-tRNAs drop off and, under limiting activity of peptidyl-tRNA hydrolase, accumulate in the cells reducing the concentration of specific aminoacylable tRNA. Therefore, the extent of inhibition is associated with the rate of starvation for a specific tRNA. Here, we used minigenes harboring various last sense codons that sequester specific tRNAs with different efficiency, to inhibit the translation of reporter genes containing, or not, these codons. A prompt inhibition of the protein synthesis directed by genes containing the codons starved for their cognate tRNA (hungry codons) was observed. However, a non-specific in vitro inhibition of protein synthesis, irrespective of the codon composition of the gene, was also evident. The degree of inhibition correlated directly with the number of hungry codons in the gene. Furthermore, a tRNA(Arg4)-sequestering minigene promoted the production of an incomplete beta-galactosidase polypeptide interrupted, during bacterial polypeptide chain elongation at sites where AGA codons were inserted in the lacZ gene suggesting ribosome pausing at the hungry codons.

  17. Are stop codons recognized by base triplets in the large ribosomal RNA subunit?

    PubMed

    Liang, Han; Landweber, Laura F; Fresco, Jacques R

    2005-10-01

    The precise mechanism of stop codon recognition in translation termination is still unclear. A previously published study by Ivanov and colleagues proposed a new model for stop codon recognition in which 3-nucleotide Ter-anticodons within the loops of hairpin helices 69 (domain IV) and 89 (domain V) in large ribosomal subunit (LSU) rRNA recognize stop codons to terminate protein translation in eubacteria and certain organelles. We evaluated this model by extensive bioinformatic analysis of stop codons and their putative corresponding Ter-anticodons across a much wider range of species, and found many cases for which it cannot explain the stop codon usage without requiring the involvement of one or more of the eight possible noncomplementary base pairs. Involvement of such base pairs may not be structurally or thermodynamically damaging to the model. However, if, according to the model, Ter-anticodon interaction with stop codons occurs within the ribosomal A-site, the structural stringency which that site imposes on sense codon.tRNA anticodon interaction should also extend to stop codon.Ter-anticodon interactions. Moreover, with Ter-tRNA in place of an aminoacyl-tRNA, for each of the various Ter-anticodons there is a sense codon that can interact with it preferentially by complementary and wobble base-pairing. Both these considerations considerably weaken the arguments put forth previously.

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

    NASA Astrophysics Data System (ADS)

    Mitarai, Namiko; Pedersen, Steen

    2013-10-01

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

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

    SciTech Connect

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

    1993-10-01

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

  20. Neural Substrates Related to Motor Memory with Multiple Timescales in Sensorimotor Adaptation

    PubMed Central

    Lv, Jinchi; Schweighofer, Nicolas; Imamizu, Hiroshi

    2015-01-01

    Recent computational and behavioral studies suggest that motor adaptation results from the update of multiple memories with different timescales. Here, we designed a model-based functional magnetic resonance imaging (fMRI) experiment in which subjects adapted to two opposing visuomotor rotations. A computational model of motor adaptation with multiple memories was fitted to the behavioral data to generate time-varying regressors of brain activity. We identified regional specificity to timescales: in particular, the activity in the inferior parietal region and in the anterior-medial cerebellum was associated with memories for intermediate and long timescales, respectively. A sparse singular value decomposition analysis of variability in specificities to timescales over the brain identified four components, two fast, one middle, and one slow, each associated with different brain networks. Finally, a multivariate decoding analysis showed that activity patterns in the anterior-medial cerebellum progressively represented the two rotations. Our results support the existence of brain regions associated with multiple timescales in adaptation and a role of the cerebellum in storing multiple internal models. PMID:26645916

  1. An Adaptive Display to Treat Stress-Related Disorders: EMMA's World

    ERIC Educational Resources Information Center

    Banos, R. M.; Botella, C.; Guillen, V.; Garcia-Palacios, A.; Quero, S.; Breton-Lopez, J.; Alcaniz, M.

    2009-01-01

    Most of the virtual environments currently available in the field of psychological treatments were designed to solve a specific problem. Our research group has developed a versatile virtual reality system (an adaptive display) called "EMMA's world", which can address a wide range of problems. It was designed to assist in clinical situations where…

  2. The Relationship between Objective and Perceived Fit with Academic Major, Adaptability, and Major-Related Outcomes

    ERIC Educational Resources Information Center

    Wessel, Jennifer L.; Ryan, Ann Marie; Oswald, Frederick L.

    2008-01-01

    This study examined the effects of fit with college major on major commitment, GPA, college satisfaction, and changing one's major. We further examined how individual adaptability may moderate the importance of fit on these outcomes. College students (N = 198; 160 women and 38 men; mean age = 19.14 years) completed an interest inventory used to…

  3. Hypoxic Adaptation during Development: Relation to Pattern of Neurological Presentation and Cognitive Disability

    ERIC Educational Resources Information Center

    Kirkham, Fenella J.; Datta, Avijit K.

    2006-01-01

    Children with acute hypoxic-ischaemic events (e.g. stroke) and chronic neurological conditions associated with hypoxia frequently present to paediatric neurologists. Failure to adapt to hypoxia may be a common pathophysiological pathway linking a number of other conditions of childhood with cognitive deficit. There is evidence that congenital…

  4. Adapting the Sheehan Disability Scale to Assess Child and Parent Impairment Related to Childhood Anxiety Disorders

    ERIC Educational Resources Information Center

    Whiteside, Stephen P.

    2009-01-01

    This study describes a child adaptation of the Sheehan Disability Scale, a measure of impairment among anxious adults. Parallel child and parent report forms were created to assess the degree to which anxiety interferes with child and parent social, educational/occupational, and family functioning. Data from 267 anxious children (140 boys ages…

  5. Interpretation of illness in cancer survivors is associated with health-related variables and adaptive coping styles

    PubMed Central

    Büssing, Arndt; Fischer, Julia

    2009-01-01

    Background A patient's interpretation of illness may have an influence on the choice of coping strategies and decision making. We intended to analyze the meaning German cancer survivors would attribute to their disease, and investigated intercorrelations between the respective interpretations, health-related variables and adaptive coping strategies. Methods In an anonymous cross-sectional survey, we analyzed the interpretations of disease (according to Lipowski's eight 'meaning of illness' categories) in 387 patients with cancer (81% breast cancer). To make statements about their conceptual relationships with health-related variables, we correlated the 8 items of the 'Interpretation of Illness' questionnaire (IIQ) with health-related quality of life, anxiety/depression, fatigue, life satisfaction, and adaptive coping strategies. Results Most cancer survivors regarded their disease as a challenge (52%), others as value (38%) or even an interruption of life (irreparable loss; 35%); weakness/failure (5%) and punishment (3%) were rated the lowest. The fatalistic negative interpretations 'interruption/loss' and 'enemy/threat' were inversely correlated with mental health-related quality of life and life satisfaction, and positively with an escape-avoidance strategy, depression and anxiety. In contrast, positive disease interpretations (i.e., 'challenge' and 'value') correlated only with adaptive coping strategies. Physical health correlated with none of the disease interpretations. Conclusion Despite conceptual limitations, the 8-item schema could be regarded as a useful screening approach to identify patients at risk for reduced psychosocial functioning. PMID:19178733

  6. Genetic Adaptation vs. Ecophysiological Plasticity of Photosynthetic-Related Traits in Young Picea glauca Trees along a Regional Climatic Gradient.

    PubMed

    Benomar, Lahcen; Lamhamedi, Mohammed S; Rainville, André; Beaulieu, Jean; Bousquet, Jean; Margolis, Hank A

    2016-01-01

    Assisted population migration (APM) is the intentional movement of populations within a species range to sites where future environmental conditions are projected to be more conducive to growth. APM has been proposed as a proactive adaptation strategy to maintain forest productivity and to reduce the vulnerability of forest ecosystems to projected climate change. The validity of such a strategy will depend on the adaptation capacity of populations, which can partially be evaluated by the ecophysiological response of different genetic sources along a climatic gradient. This adaptation capacity results from the compromise between (i) the degree of genetic adaptation of seed sources to their environment of origin and (ii) the phenotypic plasticity of functional trait which can make it possible for transferred seed sources to positively respond to new growing conditions. We examined phenotypic variation in morphophysiological traits of six seed sources of white spruce (Picea glauca [Moench] Voss) along a regional climatic gradient in Québec, Canada. Seedlings from the seed sources were planted at three forest sites representing a mean annual temperature (MAT) gradient of 2.2°C. During the second growing season, we measured height growth (H2014) and traits related to resources use efficiency and photosynthetic rate (A max). All functional traits showed an adaptive response to the climatic gradient. Traits such as H2014, A max, stomatal conductance (g s ), the ratio of mesophyll to stomatal conductance, water use efficiency, and photosynthetic nitrogen-use efficiency showed significant variation in both physiological plasticity due to the planting site and seed source variation related to local genetic adaptation. However, the amplitude of seed source variation was much less than that related to plantation sites in the area investigated. The six seed sources showed a similar level of physiological plasticity. H2014, A max and g s , but not carboxylation capacity (V

  7. Genetic Adaptation vs. Ecophysiological Plasticity of Photosynthetic-Related Traits in Young Picea glauca Trees along a Regional Climatic Gradient

    PubMed Central

    Benomar, Lahcen; Lamhamedi, Mohammed S.; Rainville, André; Beaulieu, Jean; Bousquet, Jean; Margolis, Hank A.

    2016-01-01

    Assisted population migration (APM) is the intentional movement of populations within a species range to sites where future environmental conditions are projected to be more conducive to growth. APM has been proposed as a proactive adaptation strategy to maintain forest productivity and to reduce the vulnerability of forest ecosystems to projected climate change. The validity of such a strategy will depend on the adaptation capacity of populations, which can partially be evaluated by the ecophysiological response of different genetic sources along a climatic gradient. This adaptation capacity results from the compromise between (i) the degree of genetic adaptation of seed sources to their environment of origin and (ii) the phenotypic plasticity of functional trait which can make it possible for transferred seed sources to positively respond to new growing conditions. We examined phenotypic variation in morphophysiological traits of six seed sources of white spruce (Picea glauca [Moench] Voss) along a regional climatic gradient in Québec, Canada. Seedlings from the seed sources were planted at three forest sites representing a mean annual temperature (MAT) gradient of 2.2°C. During the second growing season, we measured height growth (H2014) and traits related to resources use efficiency and photosynthetic rate (Amax). All functional traits showed an adaptive response to the climatic gradient. Traits such as H2014, Amax, stomatal conductance (gs), the ratio of mesophyll to stomatal conductance, water use efficiency, and photosynthetic nitrogen-use efficiency showed significant variation in both physiological plasticity due to the planting site and seed source variation related to local genetic adaptation. However, the amplitude of seed source variation was much less than that related to plantation sites in the area investigated. The six seed sources showed a similar level of physiological plasticity. H2014, Amax and gs, but not carboxylation capacity (Vcmax), were

  8. [Analysis on the preference of synonymous codon in VP1 nucleotide sequence of the EV71 based on RSCU method].

    PubMed

    Qi, Bin; Zhao, Jing-Jing; Gao, Lei; Zhu, Ping

    2009-11-01

    Based on RSCU method and by analyzing the preference of codon usage in VP1 nucleotide sequences of EV71 isolated in Chinese mainland and Taiwan region from 1998 to 2008, it is clear that there is an obvious time discrimination in RSCU calculated from EV71 VP1 strain between two different regions of China and it is more obvious in Taiwan region, therefore, according to the diversity of RSCU, the years can be divided into 2 intervals in Chinese mainland and 4 intervals in Taiwan region, especially, the number of intervals in one region have a positive co-relation with the activity of variation of the EV71 in the same region. The change of the preference of codon usage in VP1 nucleotide sequences of EV71 can significantly embody the Variation of the EV71, so we can make use of the analysis on preference of codon usage in VP1 nucleotide sequences of EV71 to predict the possible variation trend of the EV71.

  9. Codon Optimization to Enhance Expression Yields Insights into Chloroplast Translation1[OPEN

    PubMed Central

    Chan, Hui-Ting; Williams-Carrier, Rosalind; Barkan, Alice

    2016-01-01

    Codon optimization based on psbA genes from 133 plant species eliminated 105 (human clotting factor VIII heavy chain [FVIII HC]) and 59 (polio VIRAL CAPSID PROTEIN1 [VP1]) rare codons; replacement with only the most highly preferred codons decreased transgene expression (77- to 111-fold) when compared with the codon usage hierarchy of the psbA genes. Targeted proteomic quantification by parallel reaction monitoring analysis showed 4.9- to 7.1-fold or 22.5- to 28.1-fold increase in FVIII or VP1 codon-optimized genes when normalized with stable isotope-labeled standard peptides (or housekeeping protein peptides), but quantitation using western blots showed 6.3- to 8-fold or 91- to 125-fold increase of transgene expression from the same batch of materials, due to limitations in quantitative protein transfer, denaturation, solubility, or stability. Parallel reaction monitoring, to our knowledge validated here for the first time for in planta quantitation of biopharmaceuticals, is especially useful for insoluble or multimeric proteins required for oral drug delivery. Northern blots confirmed that the increase of codon-optimized protein synthesis is at the translational level rather than any impact on transcript abundance. Ribosome footprints did not increase proportionately with VP1 translation or even decreased after FVIII codon optimization but is useful in diagnosing additional rate-limiting steps. A major ribosome pause at CTC leucine codons in the native gene of FVIII HC was eliminated upon codon optimization. Ribosome stalls observed at clusters of serine codons in the codon-optimized VP1 gene provide an opportunity for further optimization. In addition to increasing our understanding of chloroplast translation, these new tools should help to advance this concept toward human clinical studies. PMID:27465114

  10. Populations of p53 codon 270 CGT to TGT mutant cells in SKH-1 mouse skin tumors induced by simulated solar light.

    PubMed

    Verkler, Tracie L; Delongchamp, Robert R; Couch, Letha H; Miller, Barbara J; Warbritton, Alan; Mellick, Paul W; Howard, Paul C; Parsons, Barbara L

    2008-11-01

    The p53 codon 270 CGT to TGT mutation was investigated as a biomarker of sunlight-induced mutagenesis and carcinogenesis. The relationship between tumor development and abundance of this hotspot mutation was analyzed in mouse skin tumors induced by chronic exposure to simulated solar light (SSL). The 24 tumors analyzed had similar growth kinetics, with an average doubling time of approximately 16.4 d. Levels of the p53 codon 270 mutation were quantified in the 24 mouse skin tumors using allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). All tumors contained measurable amounts of the mutation. The p53 codon 270 CGT to TGT mutant fraction (MF) ranged from 2.29 x 10(-3) to 9.42 x 10(-2), with 3.26 x 10(-2) as the median. These p53 MF measurements are lower than expected for an initiating mutation involved in the development of tumors of monoclonal origin. There was no evidence of a correlation between p53 codon 270 MF and either tumor area or an estimate of tumor cell number. Thus, the data do not support the idea that p53 mutation accumulates linearly during tumor development. To investigate how p53 mutation was distributed within tumors, 19 needle biopsies from seven different tumors were analyzed by ACB-PCR. This analysis demonstrated that p53 codon 270 mutation is heterogeneously distributed within tumors. The long-term goal of this research is to combine morphological and p53 MF measurements from tissues corresponding to the various stages of tumor development, in order to derive mathematical models relating the p53 codon 270 mutation to the development of SSL-induced skin tumors.

  11. System and method for adaptively deskewing parallel data signals relative to a clock

    DOEpatents

    Jenkins, Philip Nord; Cornett, Frank N.

    2008-10-07

    A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in detected skew.

  12. System and method for adaptively deskewing parallel data signals relative to a clock

    SciTech Connect

    Jenkins, Philip Nord; Cornett, Frank N

    2011-10-04

    A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in detected skew.

  13. Adaptation of Drosophila melanogaster to Unfavorable Growth Medium Affects Lifespan and Age-Related Fecundity.

    PubMed

    Yakovleva, E U; Naimark, E B; Markov, A V

    2016-12-01

    Experimental adaptation of Drosophila melanogaster to nutrient-deficient starch-based (S) medium resulted in lifespan shortening, increased early-life fecundity, accelerated reproductive aging, and sexually dimorphic survival curves. The direction of all these evolutionary changes coincide with the direction of phenotypic plasticity observed in non-adapted flies cultured on S medium. High adult mortality rate caused by unfavorable growth medium apparently was the main factor of selection during the evolutionary experiment. The results are partially compatible with Williams' hypothesis, which states that increased mortality rate should result in relaxed selection against mutations that decrease fitness late in life, and thus promote the evolution of shorter lifespan and earlier reproduction. However, our results do not confirm Williams' prediction that the sex with higher mortality rate should undergo more rapid aging: lifespan shortening by S medium is more pronounced in naïve males than females, but it was female lifespan that decreased more in the course of adaptation. These data, as well as the results of testing of F1 hybrids between adapted and control lineages, are compatible with the idea that the genetic basis of longevity is different in the two sexes, and that evolutionary response to increased mortality rate depends on the degree to which the mortality is selective. Selective mortality can result in the development of longer (rather than shorter) lifespan in the course of evolution. The results also imply that antagonistic pleiotropy of alleles, which increase early-life fecundity at the cost of accelerated aging, played an important role in the evolutionary changes of females in the experimental lineage, while accumulation of deleterious mutations with late-life effects due to drift was more important in the evolution of male traits.

  14. Gene expression in closely related species mirrors local adaptation: consequences for responses to a warming world.

    PubMed

    O'Neil, Shawn T; Dzurisin, Jason D K; Williams, Caroline M; Lobo, Neil F; Higgins, Jessica K; Deines, Jillian M; Carmichael, Rory D; Zeng, Erliang; Tan, John C; Wu, Grace C; Emrich, Scott J; Hellmann, Jessica J

    2014-06-01

    Local adaptation of populations could preclude or slow range expansions in response to changing climate, particularly when dispersal is limited. To investigate the differential responses of populations to changing climatic conditions, we exposed poleward peripheral and central populations of two Lepidoptera to reciprocal, common-garden climatic conditions and compared their whole-transcriptome expression. We found evidence of simple population differentiation in both species, and in the species with previously identified population structure and phenotypic local adaptation, we found several hundred genes that responded in a synchronized and localized fashion. These genes were primarily involved in energy metabolism and oxidative stress, and expression levels were most divergent between populations in the same environment in which we previously detected divergence for metabolism. We found no localized genes in the species with less population structure and for which no local adaptation was previously detected. These results challenge the assumption that species are functionally similar across their ranges and poleward peripheral populations are preadapted to warmer conditions. Rather, some taxa deserve population-level consideration when predicting the effects of climate change because they respond in genetically based, distinctive ways to changing conditions.

  15. Adaptation Duration Dissociates Category-, Image-, and Person-Specific Processes on Face-Evoked Event-Related Potentials

    PubMed Central

    Zimmer, Márta; Zbanţ, Adriana; Németh, Kornél; Kovács, Gyula

    2015-01-01

    Several studies demonstrated that face perception is biased by the prior presentation of another face, a phenomenon termed as face-related after-effect (FAE). FAE is linked to a neural signal-reduction at occipito-temporal areas and it can be observed in the amplitude modulation of the early event-related potential (ERP) components. Recently, macaque single-cell recording studies suggested that manipulating the duration of the adaptor makes the selective adaptation of different visual motion processing steps possible. To date, however, only a few studies tested the effects of adaptor duration on the electrophysiological correlates of human face processing directly. The goal of the current study was to test the effect of adaptor duration on the image-, identity-, and generic category-specific face processing steps. To this end, in a two-alternative forced choice familiarity decision task we used five adaptor durations (ranging from 200–5000 ms) and four adaptor categories: adaptor and test were identical images—Repetition Suppression (RS); adaptor and test were different images of the Same Identity (SameID); adaptor and test images depicted Different Identities (DiffID); the adaptor was a Fourier phase-randomized image (No). Behaviorally, a strong priming effect was observed in both accuracy and response times for RS compared with both DiffID and No. The electrophysiological results suggest that rapid adaptation leads to a category-specific modulation of P100, N170, and N250. In addition, both identity and image-specific processes affected the N250 component during rapid adaptation. On the other hand, prolonged (5000 ms) adaptation enhanced, and extended category-specific adaptation processes over all tested ERP components. Additionally, prolonged adaptation led to the emergence of image-, and identity-specific modulations on the N170 and P2 components as well. In other words, there was a clear dissociation among category, identity-, and image

  16. Effects of a psychophysiological system for adaptive automation on performance, workload, and the event-related potential P300 component

    NASA Technical Reports Server (NTRS)

    Prinzel, Lawrence J 3rd; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    The present study examined the effects of an electroencephalographic- (EEG-) based system for adaptive automation on tracking performance and workload. In addition, event-related potentials (ERPs) to a secondary task were derived to determine whether they would provide an additional degree of workload specificity. Participants were run in an adaptive automation condition, in which the system switched between manual and automatic task modes based on the value of each individual's own EEG engagement index; a yoked control condition; or another control group, in which task mode switches followed a random pattern. Adaptive automation improved performance and resulted in lower levels of workload. Further, the P300 component of the ERP paralleled the sensitivity to task demands of the performance and subjective measures across conditions. These results indicate that it is possible to improve performance with a psychophysiological adaptive automation system and that ERPs may provide an alternative means for distinguishing among levels of cognitive task demand in such systems. Actual or potential applications of this research include improved methods for assessing operator workload and performance.

  17. ModelOMatic: fast and automated model selection between RY, nucleotide, amino acid, and codon substitution models.

    PubMed

    Whelan, Simon; Allen, James E; Blackburne, Benjamin P; Talavera, David

    2015-01-01

    Molecular phylogenetics is a powerful tool for inferring both the process and pattern of evolution from genomic sequence data. Statistical approaches, such as maximum likelihood and Bayesian inference, are now established as the preferred methods of inference. The choice of models that a researcher uses for inference is of critical importance, and there are established methods for model selection conditioned on a particular type of data, such as nucleotides, amino acids, or codons. A major limitation of existing model selection approaches is that they can only compare models acting upon a single type of data. Here, we extend model selection to allow comparisons between models describing different types of data by introducing the idea of adapter functions, which project aggregated models onto the originally observed sequence data. These projections are implemented in the program ModelOMatic and used to perform model selection on 3722 families from the PANDIT database, 68 genes from an arthropod phylogenomic data set, and 248 genes from a vertebrate phylogenomic data set. For the PANDIT and arthropod data, we find that amino acid models are selected for the overwhelming majority of alignments; with progressively smaller numbers of alignments selecting codon and nucleotide models, and no families selecting RY-based models. In contrast, nearly all alignments from the vertebrate data set select codon-based models. The sequence divergence, the number of sequences, and the degree of selection acting upon the protein sequences may contribute to explaining this variation in model selection. Our ModelOMatic program is fast, with most families from PANDIT taking fewer than 150 s to complete, and should therefore be easily incorporated into existing phylogenetic pipelines. ModelOMatic is available at https://code.google.com/p/modelomatic/.

  18. A new turn in codon-anticodon selection through halogen bonds.

    PubMed

    Vijay Solomon, Rajadurai; Angeline Vedha, Swaminathan; Venuvanalingam, Ponnambalam

    2014-04-28

    The halogen bond is relatively a less characterized intermolecular interaction compared to the hydrogen bond and the structure, stability and electronic structures of halogenated base pairs, particularly at the wobble junction have been investigated using DFT. Three halogens, namely Cl, Br and I, have been tested for their role in such situations with uracil as the anticodon base. Computed results reveal that when halogen atoms replace protons in the hydrogen bonding positions they induce lot of geometric changes that flip some of the observed base pairs into unobserved base pairs and vice versa. NCI, NBO and AIM analyses explain these changes at the electronic level. The new codons will have lot of impact in future applications, particularly in self assembly of biomaterials and t-RNA synthetic strategies.

  19. New insights into the interplay between codon bias determinants in plants

    PubMed Central

    Camiolo, S.; Melito, S.; Porceddu, A.

    2015-01-01

    Codon bias is the non-random use of synonymous codons, a phenomenon that has been observed in species as diverse as bacteria, plants and mammals. The preferential use of particular synonymous codons may reflect neutral mechanisms (e.g. mutational bias, G|C-biased gene conversion, genetic drift) and/or selection for mRNA stability, translational efficiency and accuracy. The extent to which these different factors influence codon usage is unknown, so we dissected the contribution of mutational bias and selection towards codon bias in genes from 15 eudicots, 4 monocots and 2 mosses. We analysed the frequency of mononucleotides, dinucleotides and trinucleotides and investigated whether the compositional genomic background could account for the observed codon usage profiles. Neutral forces such as mutational pressure and G|C-biased gene conversion appeared to underlie most of the observed codon bias, although there was also evidence for the selection of optimal translational efficiency and mRNA folding. Our data confirmed the compositional differences between monocots and dicots, with the former featuring in general a lower background compositional bias but a higher overall codon bias. PMID:26546225

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously identified the mycobacterial high G+C codon usage bias as a limiting factor in heterologous expression of MAP proteins from Lb.salivarius, and demonstrated that codon optimisation of a synthetic coding gene greatly enhances MAP protein production. Here, we effectively demonstrate ...

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

    PubMed

    Nabiyouni, Maryam; Prakash, Ashwin; Fedorov, Alexei

    2013-04-25

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

  2. Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD

    PubMed Central

    Fu, Jingjing; Murphy, Katherine A.; Zhou, Mian; Li, Ying H.; Lam, Vu H.; Tabuloc, Christine A.; Chiu, Joanna C.; Liu, Yi

    2016-01-01

    Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage “code” within genetic codons to regulate cotranslational protein folding. PMID:27542830

  3. Importance of codon usage for the temporal regulation of viral gene expression

    PubMed Central

    Shin, Young C.; Bischof, Georg F.; Lauer, William A.; Desrosiers, Ronald C.

    2015-01-01

    The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products. PMID:26504241

  4. Reducing codon redundancy and screening effort of combinatorial protein libraries created by saturation mutagenesis.

    PubMed

    Kille, Sabrina; Acevedo-Rocha, Carlos G; Parra, Loreto P; Zhang, Zhi-Gang; Opperman, Diederik J; Reetz, Manfred T; Acevedo, Juan Pablo

    2013-02-15

    Saturation mutagenesis probes define sections of the vast protein sequence space. However, even if randomization is limited this way, the combinatorial numbers problem is severe. Because diversity is created at the codon level, codon redundancy is a crucial factor determining the necessary effort for library screening. Additionally, due to the probabilistic nature of the sampling process, oversampling is required to ensure library completeness as well as a high probability to encounter all unique variants. Our trick employs a special mixture of three primers, creating a degeneracy of 22 unique codons coding for the 20 canonical amino acids. Therefore, codon redundancy and subsequent screening effort is significantly reduced, and a balanced distribution of codon per amino acid is achieved, as demonstrated exemplarily for a library of cyclohexanone monooxygenase. We show that this strategy is suitable for any saturation mutagenesis methodology to generate less-redundant libraries.

  5. National and local vulnerability to climate-related disasters in Latin America: the role of social asset-based adaptation.

    PubMed

    Rubin, Oliver; Rossing, Tine

    2012-01-01

    The Latin American region is particularly prone to climate-related natural hazards. However, this article argues that natural hazards are only partly to blame for the region's vulnerability to natural disasters with quantitative evidence suggesting instead that income per capita and inequality are main determinants of natural disaster mortality in Latin America. Locally, the region's poor are particularly susceptible to climate-related natural hazards. As a result of their limited access to capital, adaptation based on social assets constitutes an effective coping strategy. Evidence from Bolivia and Belize illustrates the importance of social assets in protecting the most vulnerable against natural disasters.

  6. System and method for adaptively deskewing parallel data signals relative to a clock

    DOEpatents

    Jenkins, Philip Nord; Cornett, Frank N.

    2006-04-18

    A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. Each of the plurality of delayed signals is compared to a reference signal to detect changes in the skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in the detected skew.

  7. Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders

    PubMed Central

    Radley, Jason; Morilak, David; Viau, Victor; Campeau, Serge

    2015-01-01

    Stress responses entail neuroendocrine, autonomic, and behavioral changes to promote effective coping with real or perceived threats to one’s safety. While these responses are critical for the survival of the individual, adverse effects of repeated exposure to stress are widely known to have deleterious effects on health. Thus, a considerable effort in the search for treatments to stress-related CNS disorders necessitates unraveling the brain mechanisms responsible for adaptation under acute conditions and their perturbations following chronic stress exposure. This paper is based upon a symposium from the 2014 International Behavioral Neuroscience Meeting, summarizing some recent advances in understanding the effects of stress on adaptive and maladaptive responses subserved by limbic forebrain networks. An important theme highlighted in this review is that the same networks mediating neuroendocrine, autonomic, and behavioral processes during adaptive coping also comprise targets of the effects of repeated stress exposure in the development of maladaptive states. Where possible, reference is made to the similarity of neurobiological substrates and effects observed following repeated exposure to stress in laboratory animals and the clinical features of stress-related disorders in humans. PMID:26116544

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

    PubMed

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

    2015-10-01

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

  9. SU-E-J-57: First Development of Adapting to Intrafraction Relative Motion Between Prostate and Pelvic Lymph Nodes Targets

    SciTech Connect

    Ge, Y; Colvill, E; O’Brien, R; Keall, P; Booth, J

    2015-06-15

    Purpose Large intrafraction relative motion of multiple targets is common in advanced head and neck, lung, abdominal, gynaecological and urological cancer, jeopardizing the treatment outcomes. The objective of this study is to develop a real-time adaptation strategy, for the first time, to accurately correct for the relative motion of multiple targets by reshaping the treatment field using the multi-leaf collimator (MLC). Methods The principle of tracking the simultaneously treated but differentially moving tumor targets is to determine the new aperture shape that conforms to the shifted targets. Three dimensional volumes representing the individual targets are projected to the beam’s eye view. The leaf openings falling inside each 2D projection will be shifted according to the measured motion of each target to form the new aperture shape. Based on the updated beam shape, new leaf positions will be determined with optimized trade-off between the target underdose and healthy tissue overdose, and considerations of the physical constraints of the MLC. Taking a prostate cancer patient with pelvic lymph node involvement as an example, a preliminary dosimetric study was conducted to demonstrate the potential treatment improvement compared to the state-of- art adaptation technique which shifts the whole beam to track only one target. Results The world-first intrafraction adaptation system capable of reshaping the beam to correct for the relative motion of multiple targets has been developed. The dose in the static nodes and small bowel are closer to the planned distribution and the V45 of small bowel is decreased from 110cc to 75cc, corresponding to a 30% reduction by this technique compared to the state-of-art adaptation technique. Conclusion The developed adaptation system to correct for intrafraction relative motion of multiple targets will guarantee the tumour coverage and thus enable PTV margin reduction to minimize the high target dose to the adjacent organs

  10. Large-scale adaptive divergence in Boechera fecunda, an endangered wild relative of Arabidopsis

    PubMed Central

    Leamy, Larry J; Lee, Cheng-Ruei; Cousins, Vanessa; Mujacic, Ibro; Manzaneda, Antonio J; Prasad, Kasavajhala; Mitchell-Olds, Thomas; Song, Bao-Hua

    2014-01-01

    Many biological species are threatened with extinction because of a number of factors such as climate change and habitat loss, and their preservation depends on an accurate understanding of the extent of their genetic variability within and among populations. In this study, we assessed the genetic divergence of five quantitative traits in 10 populations of an endangered cruciferous species, Boechera fecunda, found in only several populations in each of two geographic regions (WEST and EAST) in southwestern Montana. We analyzed variation in quantitative traits, neutral molecular markers, and environmental factors and provided evidence that despite the restricted geographical distribution of this species, it exhibits a high level of genetic variation and regional adaptation. Conservation efforts therefore should be directed to the preservation of populations in each of these two regions without attempting transplantation between regions. Heritabilities and genetic coefficients of variation estimated from nested ANOVAs were generally high for leaf and rosette traits, although lower (and not significantly different from 0) for water-use efficiency. Measures of quantitative genetic differentiation, QST, were calculated for each trait from each pair of populations. For three of the five traits, these values were significantly higher between regions compared with those within regions (after adjustment for neutral genetic variation, FST). This suggested that natural selection has played an important role in producing regional divergence in this species. Our analysis also revealed that the B. fecunda populations appear to be locally adapted due, at least in part, to differences in environmental conditions in the EAST and WEST regions. PMID:25473471

  11. Sex-related adaptive responses to interaction of drought and salinity in Populus yunnanensis.

    PubMed

    Chen, Lianghua; Zhang, Sheng; Zhao, Hongxia; Korpelainen, Helena; Li, Chunyang

    2010-10-01

    We used Populus yunnanensis Dode., a native dioecious species in southwestern China, as a model species to study morphological, physiological, biochemical and ultrastructural responses to drought, salinity and their combination. Females exhibited more growth inhibition, gas exchange rate depression and reactive oxygen species (ROS) accumulation; higher lipid peroxide levels, lower osmotic adjustment capacity and ascorbate-glutathione cycle enzyme activities; and more damage to cell organelles than did males under drought, salinity and especially under their combination. In addition, we found sex-specific responses in total chlorophyll content (TC), carotenoid concentration and carbon isotope composition under different osmotic stresses. Our results indicated that: (1) females are more sensitive and suffer from greater negative effects than do males under drought, salinity and especially under their combination; (2) sexual differences in adaptive responses to drought, salinity and their combination are context dependent; and (3) sex-specific reactions under a combination of stresses are distinct from single-stress responses. Thus, these results provide evidence for adaptive differentiation between sexes in responses to osmotic stresses and in the sensitivity to environmental change.

  12. Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses.

    PubMed

    Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G

    2015-07-01

    Viruses rely completely on the hosts' machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response.

  13. Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses

    PubMed Central

    Félez-Sánchez, Marta; Trösemeier, Jan-Hendrik; Bedhomme, Stéphanie; González-Bravo, Maria Isabel; Kamp, Christel; Bravo, Ignacio G.

    2015-01-01

    Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response. PMID:26139833

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

    PubMed Central

    Esposito, Lauren A.; Gupta, Swati; Streiter, Fraida; Prasad, Ashley

    2016-01-01

    In an genomics course sponsored by the Howard Hughes Medical Institute (HHMI), undergraduate students have isolated and sequenced the genomes of more than 1,150 mycobacteriophages, creating the largest database of sequenced bacteriophages able to infect a single host, Mycobacterium smegmatis, a soil bacterium. Genomic analysis indicates that these mycobacteriophages can be grouped into 26 clusters based on genetic similarity. These clusters span a continuum of genetic diversity, with extensive genomic mosaicism among phages in different clusters. However, little is known regarding the primary hosts of these mycobacteriophages in their natural habitats, nor of their broader host ranges. As such, it is possible that the primary host of many newly isolated mycobacteriophages is not M. smegmatis, but instead a range of closely related bacterial species. However, determining mycobacteriophage host range presents difficulties associated with mycobacterial cultivability, pathogenicity and growth. Another way to gain insight into mycobacteriophage host range and ecology is through bioinformatic analysis of their genomic sequences. To this end, we examined the correlations between the codon usage biases of 199 different mycobacteriophages and those of several fully sequenced mycobacterial species in order to gain insight into the natural host range of these mycobacteriophages. We find that UPGMA clustering tends to match, but not consistently, clustering by shared nucleotide sequence identify. In addition, analysis of GC content, tRNA usage and correlations between mycobacteriophage and mycobacterial codon usage bias suggests that the preferred host of many clustered mycobacteriophages is not M. smegmatis but other, as yet unknown, members of the mycobacteria complex or closely allied bacterial species. PMID:28348827

  15. Adaptive decision making in a dynamic environment: a test of a sequential sampling model of relative judgment.

    PubMed

    Vuckovic, Anita; Kwantes, Peter J; Neal, Andrew

    2013-09-01

    Research has identified a wide range of factors that influence performance in relative judgment tasks. However, the findings from this research have been inconsistent. Studies have varied with respect to the identification of causal variables and the perceptual and decision-making mechanisms underlying performance. Drawing on the ecological rationality approach, we present a theory of the judgment and decision-making processes involved in a relative judgment task that explains how people judge a stimulus and adapt their decision process to accommodate their own uncertainty associated with those judgments. Undergraduate participants performed a simulated air traffic control conflict detection task. Across two experiments, we systematically manipulated variables known to affect performance. In the first experiment, we manipulated the relative distances of aircraft to a common destination while holding aircraft speeds constant. In a follow-up experiment, we introduced a direct manipulation of relative speed. We then fit a sequential sampling model to the data, and used the best fitting parameters to infer the decision-making processes responsible for performance. Findings were consistent with the theory that people adapt to their own uncertainty by adjusting their criterion and the amount of time they take to collect evidence in order to make a more accurate decision. From a practical perspective, the paper demonstrates that one can use a sequential sampling model to understand performance in a dynamic environment, allowing one to make sense of and interpret complex patterns of empirical findings that would otherwise be difficult to interpret using standard statistical analyses.

  16. Removable dentures and relations between their construction, adaptation and functionality role and influence on dysgeusia.

    PubMed

    Zwolak, Agnieszka; Bakalczuk, Magdalena; Leszcz, Przemysław; Szabelska, Anna; Sarna-Boś, Katarzyna; Kleinrok, Janusz

    2004-01-01

    A large foreign body inserted into oral cavity, e.g. complete denture, both lower and upper, might cause a temporary or constant dysarthia and dysgeusia. These might be reduced and even completely eliminated by proper dentures construction. Problems with normal articulation might result from construction faults, e.g. too thick denture base, incorrect denture base modelling, wrong teeth placement, lowering or excessive height occlusion. The hypogeusia has been repeatedly observed as the symptom in the course of the complete denture adaptation stage, as well as might keep further. The main role in the mechanism of occurrence of hypogeusia has the limitation of the lingual flexibility, especially of its tip, throughout the use of the complete denture. It provokes difficulties with the accurate course of its physiological activity as well as makes impossible the balancing with the tongue of the cryaesthesia, heath sensibility and tactile sense, which are blocked on the palate.

  17. Brain plasticity related to the consolidation of motor sequence learning and motor adaptation.

    PubMed

    Debas, Karen; Carrier, Julie; Orban, Pierre; Barakat, Marc; Lungu, Ovidiu; Vandewalle, Gilles; Hadj Tahar, Abdallah; Bellec, Pierre; Karni, Avi; Ungerleider, Leslie G; Benali, Habib; Doyon, Julien

    2010-10-12

    This study aimed to investigate, through functional MRI (fMRI), the neuronal substrates associated with the consolidation process of two motor skills: motor sequence learning (MSL) and motor adaptation (MA). Four groups of young healthy individuals were assigned to either (i) a night/sleep condition, in which they were scanned while practicing a finger sequence learning task or an eight-target adaptation pointing task in the evening (test) and were scanned again 12 h later in the morning (retest) or (ii) a day/awake condition, in which they were scanned on the MSL or the MA tasks in the morning and were rescanned 12 h later in the evening. As expected and consistent with the behavioral results, the functional data revealed increased test-retest changes of activity in the striatum for the night/sleep group compared with the day/awake group in the MSL task. By contrast, the results of the MA task did not show any difference in test-retest activity between the night/sleep and day/awake groups. When the two MA task groups were combined, however, increased test-retest activity was found in lobule VI of the cerebellar cortex. Together, these findings highlight the presence of both functional and structural dissociations reflecting the off-line consolidation processes of MSL and MA. They suggest that MSL consolidation is sleep dependent and reflected by a differential increase of neural activity within the corticostriatal system, whereas MA consolidation necessitates either a period of daytime or sleep and is associated with increased neuronal activity within the corticocerebellar system.

  18. The burgeoning field of transdisciplinary adaptation research in Quebec (1998-): a climate change-related public health narrative.

    PubMed

    Gosselin, Pierre; Bélanger, Diane; Lapaige, Véronique; Labbé, Yolaine

    2011-01-01

    the issues are successively explored, understood, and conceptualized for all of Quebec, and (3) problem transformation (2006-2009), which discusses major interactions among the stakeholders and the presentation of an Action Plan by a central actor, the Quebec government, in alliance with other stakeholders. In conclusion, we underline the importance, in the current context, of providing for a sustained transdisciplinary adaptation to climatic change. This paper should be helpful for (1) public health professionals confronted with establishing a transdisciplinary approach to a real-world problem other than climate change, (2) professionals in other sectors (such as public safety, built environment) confronted with climate change, who wish to implement transdisciplinary adaptive interventions and/or research, and (3) knowledge users (public and private actors; nongovernment organizations; citizens) from elsewhere in multi-contexts/environments/sectors who wish to promote complex collaborations (with us or not), collective leadership, and "transfrontier knowledge-to-action" for implementing climate change-related adaptation measures.

  19. Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin

    PubMed Central

    Knuth, Nicolas D.; Johannsen, Darcy L.; Tamboli, Robyn A.; Marks-Shulman, Pamela A.; Huizenga, Robert; Chen, Kong Y.; Abumrad, Naji N.; Ravussin, Eric; Hall, Kevin D.

    2014-01-01

    Objective To measure resting metabolic rate (RMR) and body composition changes in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise. Design and Methods We compared changes in body composition and RMR in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight and age that underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in “The Biggest Loser” weight loss competition (BLC). Results Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; p=0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [p<0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.64, p =0.003) and the decrease in circulating leptin (r = 0.61, p=0.006). Conclusions Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin. PMID:25236175

  20. A Comparative Analysis of Synonymous Codon Usage Bias Pattern in Human Albumin Superfamily

    PubMed Central

    Mirsafian, Hoda; Mat Ripen, Adiratna; Singh, Aarti; Teo, Phaik Hwan; Merican, Amir Feisal; Mohamad, Saharuddin Bin

    2014-01-01

    Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life. Though the frequency of codon usage is not equal across species and within genome in the same species, the phenomenon is non random and is tissue-specific. Several factors such as GC content, nucleotide distribution, protein hydropathy, protein secondary structure, and translational selection are reported to contribute to codon usage preference. The synonymous codon usage patterns can be helpful in revealing the expression pattern of genes as well as the evolutionary relationship between the sequences. In this study, synonymous codon usage bias patterns were determined for the evolutionarily close proteins of albumin superfamily, namely, albumin, α-fetoprotein, afamin, and vitamin D-binding protein. Our study demonstrated that the genes of the four albumin superfamily members have low GC content and high values of effective number of codons (ENC) suggesting high expressivity of these genes and less bias in codon usage preferences. This study also provided evidence that the albumin superfamily members are not subjected to mutational selection pressure. PMID:24707212

  1. Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes

    NASA Astrophysics Data System (ADS)

    Iwane, Yoshihiko; Hitomi, Azusa; Murakami, Hiroshi; Katoh, Takayuki; Goto, Yuki; Suga, Hiroaki

    2016-04-01

    In ribosomal polypeptide synthesis the library of amino acid building blocks is limited by the manner in which codons are used. Of the proteinogenic amino acids, 18 are coded for by multiple codons and therefore many of the 61 sense codons can be considered redundant. Here we report a method to reduce the redundancy of codons by artificially dividing codon boxes to create vacant codons that can then be reassigned to non-proteinogenic amino acids and thereby expand the library of genetically encoded amino acids. To achieve this, we reconstituted a cell-free translation system with 32 in vitro transcripts of transfer RNASNN (tRNASNN) (S = G or C), assigning the initiator and 20 elongator amino acids. Reassignment of three redundant codons was achieved by replacing redundant tRNASNNs with tRNASNNs pre-charged with non-proteinogenic amino acids. As a demonstration, we expressed a 32-mer linear peptide that consists of 20 proteinogenic and three non-proteinogenic amino acids, and a 14-mer macrocyclic peptide that contains more than four non-proteinogenic amino acids.

  2. Gene expression and protein length influence codon usage and rates of sequence evolution in Populus tremula.

    PubMed

    Ingvarsson, Pär K

    2007-03-01

    Codon bias is generally thought to be determined by a balance between mutation, genetic drift, and natural selection on translational efficiency. However, natural selection on codon usage is considered to be a weak evolutionary force and selection on codon usage is expected to be strongest in species with large effective population sizes. In this paper, I study associations between codon usage, gene expression, and molecular evolution at synonymous and nonsynonymous sites in the long-lived, woody perennial plant Populus tremula (Salicaceae). Using expression data for 558 genes derived from expressed sequence tags (EST) libraries from 19 different tissues and developmental stages, I study how gene expression levels within single tissues as well as across tissues affect codon usage and rates sequence evolution at synonymous and nonsynonymous sites. I show that gene expression have direct effects on both codon usage and the level of selective constraint of proteins in P. tremula, although in different ways. Codon usage genes is primarily determined by how highly expressed a genes is, whereas rates of sequence evolution are primarily determined by how widely expressed genes are. In addition to the effects of gene expression, protein length appear to be an important factor influencing virtually all aspects of molecular evolution in P. tremula.

  3. Discrimination by Escherichia coli initiation factor IF3 against initiation on non-canonical codons relies on complementarity rules.

    PubMed

    Meinnel, T; Sacerdot, C; Graffe, M; Blanquet, S; Springer, M

    1999-07-23

    Translation initiation factor IF3, one of three factors specifically required for translation initiation in Escherichia coli, inhibits initiation on any codon other than the three canonical initiation codons, AUG, GUG, or UUG. This discrimination against initiation on non-canonical codons could be due to either direct recognition of the two last bases of the codon and their cognate bases on the anticodon or to some ability to "feel" codon-anticodon complementarity. To investigate the importance of codon-anticodon complementarity in the discriminatory role of IF3, we constructed a derivative of tRNALeuthat has all the known characteristics of an initiator tRNA except the CAU anticodon. This tRNA is efficiently formylated by methionyl-tRNAfMettransformylase and charged by leucyl-tRNA synthetase irrespective of the sequence of its anticodon. These initiator tRNALeuderivatives (called tRNALI) allow initiation at all the non-canonical codons tested, provided that the complementarity between the codon and the anticodon of the initiator tRNALeuis respected. More remarkably, the discrimination by IF3, normally observed with non-canonical codons, is neutralised if a tRNALIcarrying a complementary anticodon is used for initiation. This suggests that IF3 somehow recognises codon-anticodon complementarity, at least at the second and third position of the codon, rather than some specific bases in either the codon or the anticodon.

  4. The Effect of an Alternate Start Codon on Heterologous Expression of a PhoA Fusion Protein in Mycoplasma gallisepticum.

    PubMed

    Panicker, Indu S; Browning, Glenn F; Markham, Philip F

    2015-01-01

    While the genomes of many Mycoplasma species have been sequenced, there are no collated data on translational start codon usage, and the effects of alternate start codons on gene expression have not been studied. Analysis of the annotated genomes found that ATG was the most prevalent translational start codon among Mycoplasma spp. However in Mycoplasma gallisepticum a GTG start codon is commonly used in the vlhA multigene family, which encodes a highly abundant, phase variable lipoprotein adhesin. Therefore, the effect of this alternate start codon on expression of a reporter PhoA lipoprotein was examined in M. gallisepticum. Mutation of the start codon from ATG to GTG resulted in a 2.5 fold reduction in the level of transcription of the phoA reporter, but the level of PhoA activity in the transformants containing phoA with a GTG start codon was only 63% of that of the transformants with a phoA with an ATG start codon, suggesting that GTG was a more efficient translational initiation codon. The effect of swapping the translational start codon in phoA reporter gene expression was less in M. gallisepticum than has been seen previously in Escherichia coli or Bacillus subtilis, suggesting the process of translational initiation in mycoplasmas may have some significant differences from those used in other bacteria. This is the first study of translational start codon usage in mycoplasmas and the impact of the use of an alternate start codon on expression in these bacteria.

  5. An initial evaluation of a culturally adapted social problem-solving and relational aggression prevention program for urban African-American relationally aggressive girls.

    PubMed

    Leff, Stephen S; Gullan, Rebecca Lakin; Paskewich, Brooke S; Abdul-Kabir, Saburah; Jawad, Abbas F; Grossman, Michael; Munro, Melissa A; Power, Thomas J

    2009-01-01

    Recent research demonstrating that relational aggression is associated with peer relationship difficulties, internalizing and externalizing behaviors, social processing deficits, and possibly later mental health disorders among girls has emphasized the need to address the unique expression of aggression among females. Despite these findings, almost all aggression interventions have been directed toward physically aggressive boys. In the current article, the authors describe the acceptability and initial effectiveness of a culturally adapted social problem-solving/social skills intervention for inner-city 3rd- to 5th-grade urban, African American, relationally aggressive girls called the Friend to Friend Program. The authors partnered with youth, teachers, parents, and playground supervisors to design the program, and the current study presents preliminary data suggesting that the intervention is viewed as highly acceptable by participating girls and teachers. Further, the intervention appears to have promise for decreasing at-risk girls' levels of relationally and physically aggressive behaviors, hostile attributions, and loneliness.

  6. A coordinated codon-dependent regulation of translation by Elongator

    PubMed Central

    Bauer, Fanelie; Hermand, Damien

    2012-01-01

    More than a decade ago, the purification of the form of the RNA polymerase II (PolII) engaged in elongation led to the discovery of an associated, multi-subunit (Elp1-6) complex named “Elongator” by the Svejstrup lab. Although further evidence supported the original notion that Elongator is involved in transcription, Elongator lacked some of the expected features for a regulator of the elongating PolII. The discovery by the Byström lab, based on genetic dissection, that Elongator is pivotal for tRNA modifications, and that all the reported phenotypes of Elongator mutants are suppressed by the overexpression of two tRNAs added to the confusion. The increasing range of both potential substrates and biological processes regulated by Elongator in higher eukaryotes indicates that the major challenge of the field is to determine the biologically relevant function of Elongator. Our recent proteome-wide study in fission yeast supports a coordinated codon-dependent regulation of translation by Elongator. Here we provide additional analyses extending this hypothesis to budding yeast and worm. PMID:23165209

  7. A codon deletion confers resistance to herbicides inhibiting protoporphyrinogen oxidase

    PubMed Central

    Patzoldt, William L.; Hager, Aaron G.; McCormick, Joel S.; Tranel, Patrick J.

    2006-01-01

    Herbicides that act by inhibiting protoporphyrinogen oxidase (PPO) are widely used to control weeds in a variety of crops. The first weed to evolve resistance to PPO-inhibiting herbicides was Amaranthus tuberculatus, a problematic weed in the midwestern United States that previously had evolved multiple resistances to herbicides inhibiting two other target sites. Evaluation of a PPO-inhibitor-resistant A. tuberculatus biotype revealed that resistance was a (incompletely) dominant trait conferred by a single, nuclear gene. Three genes predicted to encode PPO were identified in A. tuberculatus. One gene from the resistant biotype, designated PPX2L, contained a codon deletion that was shown to confer resistance by complementation of a hemG mutant strain of Escherichia coli grown in the presence and absence of the PPO inhibitor lactofen. PPX2L is predicted to encode both plastid- and mitochondria-targeted PPO isoforms, allowing a mutation in a single gene to confer resistance to two herbicide target sites. Unique aspects of the resistance mechanism include an amino acid deletion, rather than a substitution, and the dual-targeting nature of the gene, which may explain why resistance to PPO inhibitors has been rare. PMID:16894159

  8. A codon deletion confers resistance to herbicides inhibiting protoporphyrinogen oxidase.

    PubMed

    Patzoldt, William L; Hager, Aaron G; McCormick, Joel S; Tranel, Patrick J

    2006-08-15

    Herbicides that act by inhibiting protoporphyrinogen oxidase (PPO) are widely used to control weeds in a variety of crops. The first weed to evolve resistance to PPO-inhibiting herbicides was Amaranthus tuberculatus, a problematic weed in the midwestern United States that previously had evolved multiple resistances to herbicides inhibiting two other target sites. Evaluation of a PPO-inhibitor-resistant A. tuberculatus biotype revealed that resistance was a (incompletely) dominant trait conferred by a single, nuclear gene. Three genes predicted to encode PPO were identified in A. tuberculatus. One gene from the resistant biotype, designated PPX2L, contained a codon deletion that was shown to confer resistance by complementation of a hemG mutant strain of Escherichia coli grown in the presence and absence of the PPO inhibitor lactofen. PPX2L is predicted to encode both plastid- and mitochondria-targeted PPO isoforms, allowing a mutation in a single gene to confer resistance to two herbicide target sites. Unique aspects of the resistance mechanism include an amino acid deletion, rather than a substitution, and the dual-targeting nature of the gene, which may explain why resistance to PPO inhibitors has been rare.

  9. The FIGS (Focused Identification of Germplasm Strategy) Approach Identifies Traits Related to Drought Adaptation in Vicia faba Genetic Resources

    PubMed Central

    Khazaei, Hamid; Street, Kenneth; Bari, Abdallah; Mackay, Michael; Stoddard, Frederick L.

    2013-01-01

    Efficient methods to explore plant agro-biodiversity for climate change adaptive traits are urgently required. The focused identification of germplasm strategy (FIGS) is one such approach. FIGS works on the premise that germplasm is likely to reflect the selection pressures of the environment in which it developed. Environmental parameters describing plant germplasm collection sites are used as selection criteria to improve the probability of uncovering useful variation. This study was designed to test the effectiveness of FIGS to search a large faba bean (Vicia faba L.) collection for traits related to drought adaptation. Two sets of faba bean accessions were created, one from moisture-limited environments, and the other from wetter sites. The two sets were grown under well watered conditions and leaf morpho-physiological traits related to plant water use were measured. Machine-learning algorithms split the accessions into two groups based on the evaluation data and the groups created by this process were compared to the original climate-based FIGS sets. The sets defined by trait data were in almost perfect agreement to the FIGS sets, demonstrating that ecotypic differentiation driven by moisture availability has occurred within the faba bean genepool. Leaflet and canopy temperature as well as relative water content contributed more than other traits to the discrimination between sets, indicating that their utility as drought-tolerance selection criteria for faba bean germplasm. This study supports the assertion that FIGS could be an effective tool to enhance the discovery of new genes for abiotic stress adaptation. PMID:23667581

  10. Fine-scale geographic variation in photosynthetic-related traits of Picea glauca seedlings indicates local adaptation to climate.

    PubMed

    Benomar, Lahcen; Lamhamedi, Mohammed S; Villeneuve, Isabelle; Rainville, André; Beaulieu, Jean; Bousquet, Jean; Margolis, Hank A

    2015-08-01

    Climate-related variations in functional traits of boreal tree species can result both from physiological acclimation and genetic adaptation of local populations to their biophysical environment. To improve our understanding and prediction of the physiological and growth responses of populations to climate change, we studied the role of climate of seed origin in determining variations in functional traits and its implications for tree improvement programs for a commonly reforested boreal conifer, white spruce (Picea glauca (Moench) Voss). We evaluated growth, root-to-shoot ratio (R/S), specific leaf area (SLA), needle nitrogen (N(mass)), total non-structural carbohydrates (NSC) and photosynthetic traits of 3-year-old seedlings in a greenhouse experiment using seed from six seed orchards (SO) representing the different regions where white spruce is reforested in Québec. Height and total dry mass (TDM) were positively correlated with photosynthetic capacity (A(max)), stomatal conductance (g(s)) and mesophyll conductance (g(m)). Total dry mass, but not height growth, was strongly correlated with latitude of seed origin (SO) and associated climate variables. A(max), g(s), g(m) and more marginally, photosynthetic nitrogen-use efficiency (PNUE) were positively associated with the mean July temperature of the SO, while water use efficiency (WUE) was negatively associated. Maximum rates of carboxylation (V(cmax)), maximum rates of electron transport (J(max)), SLA, N(mass), NSC and R/S showed no pattern. Our results did not demonstrate a higher Amax for northern seed orchards, although this has been previously hypothesized as an adaptation mechanism for maintaining carbon uptake in northern regions. We suggest that gs, gm, WUE and PNUE are the functional traits most associated with fine-scale geographic clines and with the degree of local adaptation of white spruce populations to their biophysical environments. These geographic patterns may reflect in situ adaptive genetic

  11. Age-Related Impairment of Bones' Adaptive Response to Loading in Mice Is Associated With Sex-Related Deficiencies in Osteoblasts but No Change in Osteocytes†

    PubMed Central

    Meakin, Lee B; Galea, Gabriel L; Sugiyama, Toshihiro; Lanyon, Lance E; Price, Joanna S

    2014-01-01

    Bones adjust their mass and architecture to be sufficiently robust to withstand functional loading by adapting to their strain environment. This mechanism appears less effective with age, resulting in low bone mass. In male and female young adult (17-week-old) and old (19-month-old) mice, we investigated the effect of age in vivo on bones' adaptive response to loading and in vitro in primary cultures of osteoblast-like cells derived from bone cortices. Right tibias were axially loaded on alternate days for 2 weeks. Left tibias were non-loaded controls. In a separate group, the number of sclerostin-positive osteocytes and the number of periosteal osteoblasts were analyzed 24 hours after a single loading episode. The responses to strain of the primary osteoblast-like cells derived from these mice were assessed by EGR2 expression, change in cell number and Ki67 immunofluorescence. In young male and female mice, loading increased trabecular thickness and the number of trabecular connections. Increase in the number of trabecular connections was impaired with age but trabecular thickness was not. In old mice, the loading-related increase in periosteal apposition of the cortex was less than in young ones. Age was associated with a lesser loading-related increase in osteoblast number on the periosteal surface but had no effect on loading-related reduction in the number of sclerostin-positive osteocytes. In vitro, strain-related proliferation of osteoblast-like cells was lower in cells from old than young mice. Cells from aged female mice demonstrated normal entry into the cell cycle but subsequently arrested in G2 phase, reducing strain-related increases in cell number. Thus, in both male and female mice, loading-related adaptive responses are impaired with age. This impairment is different in females and males. The deficit appears to occur in osteoblasts' proliferative responses to strain rather than earlier strain-related responses in the osteocytes. © 2014 The Authors

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

    PubMed

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

    2016-02-19

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

  13. Tryptophan Codon-Dependent Transcription in Chlamydia pneumoniae during Gamma Interferon-Mediated Tryptophan Limitation

    PubMed Central

    Rueden, Kelsey J.; Rucks, Elizabeth A.

    2016-01-01

    In evolving to an obligate intracellular niche, Chlamydia has streamlined its genome by eliminating superfluous genes as it relies on the host cell for a variety of nutritional needs like amino acids. However, Chlamydia can experience amino acid starvation when the human host cell in which the bacteria reside is exposed to interferon gamma (IFN-γ), which leads to a tryptophan (Trp)-limiting environment via induction of the enzyme indoleamine-2,3-dioxygenase (IDO). The stringent response is used to respond to amino acid starvation in most bacteria but is missing from Chlamydia. Thus, how Chlamydia, a Trp auxotroph, responds to Trp starvation in the absence of a stringent response is an intriguing question. We previously observed that C. pneumoniae responds to this stress by globally increasing transcription while globally decreasing translation, an unusual response. Here, we sought to understand this and hypothesized that the Trp codon content of a given gene would determine its transcription level. We quantified transcripts from C. pneumoniae genes that were either rich or poor in Trp codons and found that Trp codon-rich transcripts were increased, whereas those that lacked Trp codons were unchanged or even decreased. There were exceptions, and these involved operons or large genes with multiple Trp codons: downstream transcripts were less abundant after Trp codon-rich sequences. These data suggest that ribosome stalling on Trp codons causes a negative polar effect on downstream sequences. Finally, reassessing previous C. pneumoniae microarray data based on codon content, we found that upregulated transcripts were enriched in Trp codons, thus supporting our hypothesis. PMID:27400720

  14. NEAR-INFRARED ADAPTIVE OPTICS IMAGING OF INFRARED LUMINOUS GALAXIES: THE BRIGHTEST CLUSTER MAGNITUDE-STAR FORMATION RATE RELATION

    SciTech Connect

    Randriamanakoto, Z.; Väisänen, P.; Escala, A.; Kankare, E.; Kotilainen, J.; Mattila, S.; Ryder, S.

    2013-10-01

    We have established a relation between the brightest super star cluster (SSC) magnitude in a galaxy and the host star formation rate (SFR) for the first time in the near-infrared (NIR). The data come from a statistical sample of ∼40 luminous IR galaxies (LIRGs) and starbursts utilizing K-band adaptive optics imaging. While expanding the observed relation to longer wavelengths, less affected by extinction effects, it also pushes to higher SFRs. The relation we find, M{sub K} ∼ –2.6log SFR, is similar to that derived previously in the optical and at lower SFRs. It does not, however, fit the optical relation with a single optical to NIR color conversion, suggesting systematic extinction and/or age effects. While the relation is broadly consistent with a size-of-sample explanation, we argue physical reasons for the relation are likely as well. In particular, the scatter in the relation is smaller than expected from pure random sampling strongly suggesting physical constraints. We also derive a quantifiable relation tying together cluster-internal effects and host SFR properties to possibly explain the observed brightest SSC magnitude versus SFR dependency.

  15. Kansas Adapted/Special Physical Education Test Manual. Health Related Fitness and Psychomotor Testing.

    ERIC Educational Resources Information Center

    Johnson, Robert E.; Lavay, Barry

    This manual was developed to address the need for health-related physical fitness testing of children with special needs. The first section defines the components of health-related physical fitness which consist of: (1)abdominal strength and endurance measured by a sit-up test; (2) flexibility, measured by a sit and reach test; (3) upper body…

  16. How Adaptive and Maladaptive Perfectionism Relate to Positive and Negative Psychological Functioning: Testing a Stress-Mediation Model in Black and White Female College Students

    ERIC Educational Resources Information Center

    Chang, Edward C.; Watkins, Angela; Banks, Kira Hudson

    2004-01-01

    This study assessed racial variations in how adaptive and maladaptive perfectionism relate to psychological functioning in a sample of 150 Black and 150 White female college students. Comparative results indicated that Black women, as compared with White women, reported less adaptive perfectionism, less life satisfaction, greater stress, and…

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

    PubMed Central

    Grantham, R; Gautier, C; Gouy, M

    1980-01-01

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

  18. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations

    PubMed Central

    Keane, Michael; Craig, Thomas; Alföldi, Jessica; Berlin, Aaron M.; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M.; de Magalhães, João Pedro

    2014-01-01

    Motivation: The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. Results: We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat’s extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource (http://www.naked-mole-rat.org), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species. Availability and implementation: The Naked Mole Rat Genome Resource is freely available online at http://www.naked-mole-rat.org. This resource is open source and the source code is available at https://github.com/maglab/naked-mole-rat-portal. Contact: jp@senescence.info PMID:25172923

  19. Moderate exercise training induces ROS-related adaptations to skeletal muscles.

    PubMed

    Abruzzo, P M; Esposito, F; Marchionni, C; di Tullio, S; Belia, S; Fulle, S; Veicsteinas, A; Marini, M

    2013-08-01

    Aim of the present work was the evaluation of the effects of moderate exercise training on 2 skeletal muscles differing in fibre-type composition, Tibialis Anterior (TA) and Soleus (SOL). Fibre adaptations, including their metabolic shift and mechanisms underlying proliferation and differentiation, oxidative stress markers, antioxidant and cytoprotective molecules, activity of Ca2+-handling molecules were examined. 6 male 2-month-old rats trained on a treadmill for 1 h/day, 3 days/week, for 14 weeks, reaching 30 m/min at the end of training. 6 age-matched sedentary rats served as controls. Rats were sacrificed 24 h after the last training session. Muscle regulatory factors increased in both muscles, activating satellite cell proliferation, which led to moderate hypertrophy in SOL and to moderate hyperplasia in TA, where the upregulation of desmin and TNFR2 expression suggests that myotube formation by proliferating myoblasts is somehow delayed. Changes leading to a more oxidative metabolism together with the upregulation of a number of antioxidant enzymes occurred in TA. HSP70i protein was upregulated in both SOL and TA, while oxidative stress markers increased in SOL alone. The status of ionic channels and pumps was preserved. We suggest that the increase in ROS, known to be associated with exercise, underlies most observed results.

  20. Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.

    PubMed

    Feller, Liviu; Khammissa, Razia Abdool Gafaar; Lemmer, Johan

    2017-01-01

    Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.

  1. Spanish translation, cross-cultural adaptation, and validation of the Questionnaire for Diabetes-Related Foot Disease (Q-DFD)

    PubMed Central

    Castillo-Tandazo, Wilson; Flores-Fortty, Adolfo; Feraud, Lourdes; Tettamanti, Daniel

    2013-01-01

    Purpose To translate, cross-culturally adapt, and validate the Questionnaire for Diabetes-Related Foot Disease (Q-DFD), originally created and validated in Australia, for its use in Spanish-speaking patients with diabetes mellitus. Patients and methods The translation and cross-cultural adaptation were based on international guidelines. The Spanish version of the survey was applied to a community-based (sample A) and a hospital clinic-based sample (samples B and C). Samples A and B were used to determine criterion and construct validity comparing the survey findings with clinical evaluation and medical records, respectively; while sample C was used to determine intra- and inter-rater reliability. Results After completing the rigorous translation process, only four items were considered problematic and required a new translation. In total, 127 patients were included in the validation study: 76 to determine criterion and construct validity and 41 to establish intra- and inter-rater reliability. For an overall diagnosis of diabetes-related foot disease, a substantial level of agreement was obtained when we compared the Q-DFD with the clinical assessment (kappa 0.77, sensitivity 80.4%, specificity 91.5%, positive likelihood ratio [LR+] 9.46, negative likelihood ratio [LR−] 0.21); while an almost perfect level of agreement was obtained when it was compared with medical records (kappa 0.88, sensitivity 87%, specificity 97%, LR+ 29.0, LR− 0.13). Survey reliability showed substantial levels of agreement, with kappa scores of 0.63 and 0.73 for intra- and inter-rater reliability, respectively. Conclusion The translated and cross-culturally adapted Q-DFD showed good psychometric properties (validity, reproducibility, and reliability) that allow its use in Spanish-speaking diabetic populations. PMID:24039434

  2. Testing local host adaptation and phenotypic plasticity in a herbivore when alternative related host plants occur sympatrically.

    PubMed

    Ruiz-Montoya, Lorena; Núñez-Farfán, Juan

    2013-01-01

    Host race formation in phytophagous insects can be an early stage of adaptive speciation. However, the evolution of phenotypic plasticity in host use is another possible outcome. Using a reciprocal transplant experiment we tested the hypothesis of local adaptation in the aphid Brevicoryne brassicae. Aphid genotypes derived from two sympatric host plants, Brassica oleracea and B. campestris, were assessed in order to measure the extent of phenotypic plasticity in morphological and life history traits in relation to the host plants. We obtained an index of phenotypic plasticity for each genotype. Morphological variation of aphids was summarized by principal components analysis. Significant effects of recipient host on morphological variation and life history traits (establishment, age at first reproduction, number of nymphs, and intrinsic growth rate) were detected. We did not detected genotype × host plant interaction; in general the genotypes developed better on B. campestris, independent of the host plant species from which they were collected. Therefore, there was no evidence to suggest local adaptation. Regarding plasticity, significant differences among genotypes in the index of plasticity were detected. Furthermore, significant selection on PC1 (general aphid body size) on B. campestris, and on PC1 and PC2 (body length relative to body size) on B. oleracea was detected. The elevation of the reaction norm of PC1 and the slope of the reaction norm for PC2 (i.e., plasticity) were under directional selection. Thus, host plant species constitute distinct selective environments for B. brassicae. Aphid genotypes expressed different phenotypes in response to the host plant with low or nil fitness costs. Phenotypic plasticity and gene flow limits natural selection for host specialization promoting the maintenance of genetic variation in host exploitation.

  3. Testing Local Host Adaptation and Phenotypic Plasticity in a Herbivore When Alternative Related Host Plants Occur Sympatrically

    PubMed Central

    Ruiz-Montoya, Lorena; Núñez-Farfán, Juan

    2013-01-01

    Host race formation in phytophagous insects can be an early stage of adaptive speciation. However, the evolution of phenotypic plasticity in host use is another possible outcome. Using a reciprocal transplant experiment we tested the hypothesis of local adaptation in the aphid Brevicoryne brassicae. Aphid genotypes derived from two sympatric host plants, Brassica oleracea and B. campestris, were assessed in order to measure the extent of phenotypic plasticity in morphological and life history traits in relation to the host plants. We obtained an index of phenotypic plasticity for each genotype. Morphological variation of aphids was summarized by principal components analysis. Significant effects of recipient host on morphological variation and life history traits (establishment, age at first reproduction, number of nymphs, and intrinsic growth rate) were detected. We did not detected genotype × host plant interaction; in general the genotypes developed better on B. campestris, independent of the host plant species from which they were collected. Therefore, there was no evidence to suggest local adaptation. Regarding plasticity, significant differences among genotypes in the index of plasticity were detected. Furthermore, significant selection on PC1 (general aphid body size) on B. campestris, and on PC1 and PC2 (body length relative to body size) on B. oleracea was detected. The elevation of the reaction norm of PC1 and the slope of the reaction norm for PC2 (i.e., plasticity) were under directional selection. Thus, host plant species constitute distinct selective environments for B. brassicae. Aphid genotypes expressed different phenotypes in response to the host plant with low or nil fitness costs. Phenotypic plasticity and gene flow limits natural selection for host specialization promoting the maintenance of genetic variation in host exploitation. PMID:24265743

  4. Climate Change Adaptation and Climate Related Disaster Risk Reduction Strategies in Zimbabwe and Malawi

    NASA Astrophysics Data System (ADS)

    Mubaya, C. P.; Ngepah, N.; Seyama, W.

    2015-12-01

    Climate Change Adaptation (CCA) and Disaster Risk Reduction (DRR) have similar aims and mutual benefits, and there is a very strong rationale for adopting a more integrated approach to these issues rather than analysing each of them as distinct from the other. One of the gaps that have been noted in this context is the lack of evidence in systematic integration of CCA and DRR in Southern Africa. In this regard, this study builds on understanding CCA and DRR policies from the perspectives of vulnerable groups- women and smallholder farmers, and conducts institutional and policy analysis of CCA and DRR in southern Africa, with specific focus on Malawi and Zimbabwe. Both quantitative and qualitative methodologies were employed to collect data for this study in the two countries. The analysis is centred on the conceptualization of DRR in the context of recovery time and CCA on livelihood changes. Findings of the study show that drought is no longer viewed as a hazard as it is a perennial and chronic occurrence in selected climate hotspots, with heightened intensity in certain identified years. Households are able to quickly recover from slow onset hazards such as droughts and dry spells more than they are able to recover from sudden onset floods, implying more capacity towards CCA than DRR. Government programmes and policies are also focused more on CCA than on DRR efforts that appear not to be a priority. Findings point towards female vulnerability from perceptions and practice where males tend to dominate where they are set to benefit from external assistance. We need to strengthen government capacity in implementation of DRR programmes, which is currently limited and development initiatives must deliberately target building the resilience of women.

  5. Enhancing functional expression of codon-optimized heterologous enzymes in Escherichia coli BL21(DE3) by selective introduction of synonymous rare codons.

    PubMed

    Zhong, Chao; Wei, Ping; Zhang, Yi-Heng Percival

    2017-05-01

    Rare codon in a heterologous gene may cause premature termination of protein synthesis, misincorporation of amino acids, and/or slow translation of mRNA, decreasing the heterologous protein expression. However, its hypothetical function pertaining to functional protein folding has been barely reported. Here, we investigated the effects of selective introduction of synonymous rare codons (SRCs) to two codon-optimized (i.e., rare codon-free) genes sucrose phosphorylase (SP) gene from Thermoanaerobacterium thermosaccharolyticum and amidohydrolase gene from Streptomyces caatingaensis on their expression levels in Escherichia coli BL21(DE3). We investigated the introduction of a single SRC to the coding regions of alpha-helix, beta-strand, or linker in the first half of rare codon-free sp and ah gene. The introduction of a single SRC in the beginning of the coding regions of beta-strand greatly enhanced their soluble expression levels as compared to the other regions. Also, we applied directed evolution to test multi-SRC-containing sp gene mutants for enhanced soluble SP expression levels. To easily identify the soluble SP expression level of colonies growing on Petri dishes, mCherry fluorescent protein was used as a SP-folding reporter when it was fused to the 3' end of the sp gene mutant libraries. After three rounds of screening, the best sp gene mutant containing nine SRCs exhibited an approximately six-fold enhancement in soluble protein expression level as compared to the wild-type and rare codon-free sp control. This study suggests that the selective introduction of SRCs can attenuate translation at specific points and such discontinuous attenuation can temporally separate the translation of segments of the peptide chains and actively coordinates their co-translational folding, resulting in enhanced functional protein expression. Biotechnol. Bioeng. 2017;114: 1054-1064. © 2016 Wiley Periodicals, Inc.

  6. Spatiotemporal characteristics of form analysis in the human visual cortex revealed by rapid event-related fMRI adaptation.

    PubMed

    Kourtzi, Zoe; Huberle, Elisabeth

    2005-11-01

    The integration of local elements to coherent forms is at the core of understanding visual perception. Accumulating evidence suggests that both early retinotopic and higher occipitotemporal areas contribute to the integration of local elements to global forms. However, the spatiotemporal characteristics of form analysis in the human visual cortex remain largely unknown. The aim of this study was to investigate form analysis at different spatial (global vs. local structure) and temporal (different stimulus presentation rates) scales across stages of visual analysis (from V1 to the lateral occipital complex-LOC) in the human brain. We used closed contours rendered by Gabor elements and manipulated either the global contour structure or the orientation of the local Gabor elements. Our rapid event-related fMRI adaptation studies suggest that contour integration and form processing in early visual areas is transient and limited within the local neighborhood of their cells' receptive field. In contrast, higher visual areas appear to process the perceived global form in a more sustained manner. Finally, we demonstrate that these spatiotemporal properties of form processing in the visual cortex are modulated by attention. Attention to the global form maintains sustained processing in occipitotemporal areas, whereas attention to local elements enhances their integration in early visual areas. These findings provide novel neuroimaging evidence for form analysis at different spatiotemporal scales across human visual areas and validate the use of rapid event-related fMRI adaptation for investigating processing across stages of visual analysis in the human brain.

  7. Relations between adaptive and maladaptive pain cognitions and within-day pain exacerbations in individuals with fibromyalgia.

    PubMed

    Taylor, Shannon Stark; Davis, Mary C; Yeung, Ellen W; Zautra, Alex J; Tennen, Howard A

    2016-11-16

    The objectives of this study were to assess within-person hypotheses regarding temporal cognition-pain associations: (1) do morning pain flares predict changes in two afternoon adaptive and maladaptive pain-related cognitions, and (2) do these changes in afternoon cognitions predict changes in end-of-day pain reports, which in turn, carry over to predict next morning pain in individuals with fibromyalgia. Two hundred twenty individuals with fibromyalgia completed electronic assessments of pain intensity, pain catastrophizing, and pain coping efficacy three times a day for three weeks. Multilevel structural equation modeling established that afternoon catastrophizing and coping efficacy were parallel mediators linking late morning with end-of-day pain reports (controlling for afternoon pain), in line with prediction. Catastrophizing was a stronger mediator than coping efficacy. Moreover, afternoon cognitions and end-of-day pain reports served as sequential mediators of the relation between same-day and next-day morning pain. These findings align with assertions of cognitive-behavioral theories of pain that pain flares predict changes in pain both adaptive and maladaptive cognitions, which in turn, predict further changes in pain.

  8. Alteration in expression of hormone-related genes in wild emmer wheat roots associated with drought adaptation mechanisms.

    PubMed

    Krugman, Tamar; Peleg, Zvi; Quansah, Lydia; Chagué, Véronique; Korol, Abraham B; Nevo, Eviatar; Saranga, Yehoshua; Fait, Aaron; Chalhoub, Boulos; Fahima, Tzion

    2011-12-01

    Transcriptomic and metabolomic profiles were used to unravel drought adaptation mechanisms in wild emmer wheat (Triticum turgidum ssp. dicoccoides), the progenitor of cultivated wheat, by comparing the response to drought stress in roots of genotypes contrasting in drought tolerance. The differences between the drought resistant (R) and drought susceptible (S) genotypes were characterized mainly by shifts in expression of hormone-related genes (e.g., gibberellins, abscisic acid (ABA) and auxin), including biosynthesis, signalling and response; RNA binding; calcium (calmodulin, caleosin and annexin) and phosphatidylinositol signalling, in the R genotype. ABA content in the roots of the R genotype was higher in the well-watered treatment and increased in response to drought, while in the S genotype ABA was invariant. The metabolomic profiling revealed in the R genotype a higher accumulation of tricarboxylic acid cycle intermediates and drought-related metabolites, including glucose, trehalose, proline and glycine. The integration of transcriptomics and metabolomics results indicated that adaptation to drought included efficient regulation and signalling pathways leading to effective bio-energetic processes, carbon metabolism and cell homeostasis. In conclusion, mechanisms of drought tolerance were identified in roots of wild emmer wheat, supporting our previous studies on the potential of this genepool as a valuable source for novel candidate genes to improve drought tolerance in cultivated wheat.

  9. Adaptive Neuro-Fuzzy Determination of the Effect of Experimental Parameters on Vehicle Agent Speed Relative to Vehicle Intruder

    PubMed Central

    Shamshirband, Shahaboddin; Banjanovic-Mehmedovic, Lejla; Bosankic, Ivan; Kasapovic, Suad; Abdul Wahab, Ainuddin Wahid Bin

    2016-01-01

    Intelligent Transportation Systems rely on understanding, predicting and affecting the interactions between vehicles. The goal of this paper is to choose a small subset from the larger set so that the resulting regression model is simple, yet have good predictive ability for Vehicle agent speed relative to Vehicle intruder. The method of ANFIS (adaptive neuro fuzzy inference system) was applied to the data resulting from these measurements. The ANFIS process for variable selection was implemented in order to detect the predominant variables affecting the prediction of agent speed relative to intruder. This process includes several ways to discover a subset of the total set of recorded parameters, showing good predictive capability. The ANFIS network was used to perform a variable search. Then, it was used to determine how 9 parameters (Intruder Front sensors active (boolean), Intruder Rear sensors active (boolean), Agent Front sensors active (boolean), Agent Rear sensors active (boolean), RSSI signal intensity/strength (integer), Elapsed time (in seconds), Distance between Agent and Intruder (m), Angle of Agent relative to Intruder (angle between vehicles °), Altitude difference between Agent and Intruder (m)) influence prediction of agent speed relative to intruder. The results indicated that distance between Vehicle agent and Vehicle intruder (m) and angle of Vehicle agent relative to Vehicle Intruder (angle between vehicles °) is the most influential parameters to Vehicle agent speed relative to Vehicle intruder. PMID:27219539

  10. Adaptive Neuro-Fuzzy Determination of the Effect of Experimental Parameters on Vehicle Agent Speed Relative to Vehicle Intruder.

    PubMed

    Shamshirband, Shahaboddin; Banjanovic-Mehmedovic, Lejla; Bosankic, Ivan; Kasapovic, Suad; Abdul Wahab, Ainuddin Wahid Bin

    2016-01-01

    Intelligent Transportation Systems rely on understanding, predicting and affecting the interactions between vehicles. The goal of this paper is to choose a small subset from the larger set so that the resulting regression model is simple, yet have good predictive ability for Vehicle agent speed relative to Vehicle intruder. The method of ANFIS (adaptive neuro fuzzy inference system) was applied to the data resulting from these measurements. The ANFIS process for variable selection was implemented in order to detect the predominant variables affecting the prediction of agent speed relative to intruder. This process includes several ways to discover a subset of the total set of recorded parameters, showing good predictive capability. The ANFIS network was used to perform a variable search. Then, it was used to determine how 9 parameters (Intruder Front sensors active (boolean), Intruder Rear sensors active (boolean), Agent Front sensors active (boolean), Agent Rear sensors active (boolean), RSSI signal intensity/strength (integer), Elapsed time (in seconds), Distance between Agent and Intruder (m), Angle of Agent relative to Intruder (angle between vehicles °), Altitude difference between Agent and Intruder (m)) influence prediction of agent speed relative to intruder. The results indicated that distance between Vehicle agent and Vehicle intruder (m) and angle of Vehicle agent relative to Vehicle Intruder (angle between vehicles °) is the most influential parameters to Vehicle agent speed relative to Vehicle intruder.

  11. Appropriate Relational Messages in Direct Selling Interaction: Should Salespeople Adapt to Buyers' Communicator Style?

    ERIC Educational Resources Information Center

    Comstock, Jamie; Higgins, Gary

    1997-01-01

    Prescribes rules for appropriate behavior for the direct sales relationship. Suggests that sellers may not completely understand these rules. Determines that buyers prefer sellers who are trustworthy, composed, and task-oriented. Shows that sellers are well aware of buyers' preferences for task-related interaction but may overestimate the value of…

  12. Mal-Adaptation of Event-Related EEG Responses Preceding Performance Errors

    PubMed Central

    Eichele, Heike; Juvodden, Hilde T.; Ullsperger, Markus; Eichele, Tom

    2010-01-01

    Recent EEG and fMRI evidence suggests that behavioral errors are foreshadowed by systematic changes in brain activity preceding the outcome by seconds. In order to further characterize this type of error precursor activity, we investigated single-trial event-related EEG activity from 70 participants performing a modified Eriksen flanker task, in particular focusing on the trial-by-trial dynamics of a fronto-central independent component that previously has been associated with error and feedback processing. The stimulus-locked peaks in the N2 and P3 latency range in the event-related averages showed expected compatibility and error-related modulations. In addition, a small pre-stimulus negative slow wave was present at erroneous trials. Significant error-preceding activity was found in local stimulus sequences with decreased conflict in the form of less negativity at the N2 latency (310–350 ms) accumulating across five trials before errors; concomitantly response times were speeding across trials. These results illustrate that error-preceding activity in event-related EEG is associated with the performance monitoring system and we conclude that the dynamics of performance monitoring contribute to the generation of error-prone states in addition to the more remote and indirect effects in ongoing activity such as posterior alpha power in EEG and default mode drifts in fMRI. PMID:20740080

  13. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    ERIC Educational Resources Information Center

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  14. Traffic-Related Air Pollution, Blood Pressure, and Adaptive Response of Mitochondrial Abundance

    PubMed Central

    Zhong, Jia; Cayir, Akin; Trevisi, Letizia; Sanchez-Guerra, Marco; Lin, Xinyi; Peng, Cheng; Bind, Marie-Abèle; Prada, Diddier; Laue, Hannah; Brennan, Kasey J.M.; Dereix, Alexandra; Sparrow, David; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.

    2015-01-01

    Background Exposure to black carbon (BC), a tracer of vehicular-traffic-pollution, is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can inform prevention. We evaluated the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox-imbalance, in the BC-BP relationship. Methods and Results At one or more visits among 675 older men from the Normative Aging Study (observations=1,252), we assessed daily BP and ambient BC levels from a stationary monitor. To determine blood mitochondrial abundance, we used whole blood to analyze mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase-chain-reaction. Every standard deviation (SD) increase in 28-day BC moving average (MA) was associated with 1.97 mm Hg (95%CI, 1.23–2.72; P<0.0001) and 3.46 mm Hg (95%CI, 2.06–4.87; P<0.0001) higher diastolic and systolic (SBP) BP, respectively. Positive BC-BP associations existed throughout all time windows. BC MAs (5-day to 28-day) were associated with increased mtDNA/nDNA; every SD increase in 28-day BC MA was associated with 0.12 SD (95%CI, 0.03–0.20; P=0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-SBP association throughout all time windows. The estimated effect of 28-day BC MA on SBP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95%CI, 3.03–6.33; P<0.0001), compared to the top quartile midpoint (2.40 mm Hg; 95%CI, 0.81–3.99; P=0.003). Conclusions In older adults, short- to moderate-term ambient BC levels were associated with increased BP and blood mitochondrial abundance. Our findings indicate that increased blood mitochondrial abundance is a compensatory response and attenuates the cardiac effects of BC. PMID:26660284

  15. Understanding the influence of codon translation rates on cotranslational protein folding.

    PubMed

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

    2014-05-20

    Protein domains can fold into stable tertiary structures while they are synthesized by the ribosome in a process known as cotranslational folding. If a protein does not fold cotranslationally, however, it has the opportunity to do so post-translationally, that is, after the nascent chain has been fully synthesized and released from the ribosome. The rate at which a ribosome adds an amino acid encoded by a particular codon to the elongating nascent chain can vary significantly and is called the codon translation rate. Recent experiments have illustrated the profound impact that codon translation rates can have on the cotranslational folding process and the acquisition of function by nascent proteins. Synonymous codon mutations in an mRNA molecule change the chemical identity of a codon and its translation rate without changing the sequence of the synthesized protein. This change in codon translation rate can, however, cause a nascent protein to malfunction as a result of cotranslational misfolding. In some situations, such dysfunction can have profound implications; for example, it can alter the substrate specificity of an ABC transporter protein, resulting in patients who are nonresponsive to chemotherapy treatment. Thus, codon translation rates are crucial in coordinating protein folding in a cellular environment and can affect downstream cellular processes that depend on the proper functioning of newly synthesized proteins. As the importance of codon translation rates makes clear, a necessary aspect of fully understanding cotranslational folding lies in considering the kinetics of the process in addition to its thermodynamics. In this Account, we examine the contributions that have been made to elucidating the mechanisms of cotranslational folding by using the theoretical and computational tools of chemical kinetics, molecular simulations, and systems biology. These efforts have extended our ability to understand, model, and predict the influence of codon

  16. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M.; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B.; Schlesewsky, Matthias

    2015-01-01

    Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60–81 years; n = 40) as they read sentences of the form “The opposite of black is white/yellow/nice.” Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (“white”; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, “nice,” versus the incongruous associated condition, “yellow”). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to

  17. Molecular Phylogeny of Sequenced Saccharomycetes Reveals Polyphyly of the Alternative Yeast Codon Usage

    PubMed Central

    Mühlhausen, Stefanie; Kollmar, Martin

    2014-01-01

    The universal genetic code defines the translation of nucleotide triplets, called codons, into amino acids. In many Saccharomycetes a unique alteration of this code affects the translation of the CUG codon, which is normally translated as leucine. Most of the species encoding CUG alternatively as serine belong to the Candida genus and were grouped into a so-called CTG clade. However, the “Candida genus” is not a monophyletic group and several Candida species are known to use the standard CUG translation. The codon identity could have been changed in a single branch, the ancestor of the Candida, or to several branches independently leading to a polyphyletic alternative yeast codon usage (AYCU). In order to resolve the monophyly or polyphyly of the AYCU, we performed a phylogenomics analysis of 26 motor and cytoskeletal proteins from 60 sequenced yeast species. By investigating the CUG codon positions with respect to sequence conservation at the respective alignment positions, we were able to unambiguously assign the standard code or AYCU. Quantitative analysis of the highly conserved leucine and serine alignment positions showed that 61.1% and 17% of the CUG codons coding for leucine and serine, respectively, are at highly conserved positions, whereas only 0.6% and 2.3% of the CUG codons, respectively, are at positions conserved in the respective other amino acid. Plotting the codon usage onto the phylogenetic tree revealed the polyphyly of the AYCU with Pachysolen tannophilus and the CTG clade branching independently within a time span of 30–100 Ma. PMID:25646540

  18. Adaptive memory: the survival scenario enhances item-specific processing relative to a moving scenario.

    PubMed

    Burns, Daniel J; Hart, Joshua; Griffith, Samantha E; Burns, Amy D

    2013-01-01

    Nairne, Thompson, and Pandeirada (2007) found that retention of words rated for their relevance to survival is superior to that of words encoded under numerous other deep processing conditions. They suggested that our memory systems might have evolved to confer an advantage for survival-relevant information. Burns, Burns, and Hwang (2011) suggested a two-process explanation of the proximate mechanisms responsible for the survival advantage. Whereas most control tasks encourage only one type of processing, the survival task encourages both item-specific and relational processing. They found that when control tasks encouraged both types of processing, the survival processing advantage was eliminated. However, none of their control conditions included non-survival scenarios (e.g., moving, vacation, etc.), so it is not clear how this two-process explanation would explain the survival advantage when scenarios are used as control conditions. The present experiments replicated the finding that the survival scenario improves recall relative to a moving scenario in both a between-lists and within-list design and also provided evidence that this difference was accompanied by an item-specific processing difference, not a difference in relational processing. The implications of these results for several existing accounts of the survival processing effect are discussed.

  19. Adaptation of WHOQOL as health-related quality of life instrument to develop a vision-specific instrument.

    PubMed

    Dandona, R; Dandona, L; McCarty, C A; Rao, G N

    2000-03-01

    The WHOQOL instrument was adapted as a health-related QOL instrument for a population-based epidemiologic study of eye diseases in southern India, the Andhra Pradesh Eye Disease Study (APEDS). A follow-up question was added to each item in WHOQOL to determine whether the decrease in QOL was due to any health reasons including eye-related reasons. Modifications in WHOQOL and translation in local language were done through the use of the focus groups including health professionals and people not related to health care. The modified instrument has 28 items across 6 domains of the WHOQOL and was translated into the local language, Telugu, using the pragmatic approach. It takes 10-20 minutes to be administered by a trained interviewer. Reliability was within acceptable range. This health-related QOL instrument is being used in the population-based study APEDS to develop a vision-specific QOL instrument which could potentially be used to assess the impact of visual impairment on QOL across different cultures and for use in evaluating eye-care interventions. This health-related QOL instrument could also be used to develop other disease-specific instruments as it allows assessment of the extent to which various aspects of QOL are affected by a variety of health problems.

  20. The TP53 Codon 72 Polymorphism and Risk of Sporadic Prostate Cancer among Iranian Patients

    PubMed Central

    BABAEI, Farhad; AHMADI, Seyed Ali; ABIRI, Ramin; REZAEI, Farhad; NASERI, Maryam; MAHMOUDI, Mahmoud; NATEGH, Rakhshande; MOKHTARI AZAD, Talat

    2014-01-01

    Abstract Background The TP53 gene is one of the most frequently mutated genes amongst human malignancies, particularly TP53 codon 72 polymorphism. Furthermore, an association between the TP53 codon 72 variants and prostate cancer has been reported in several studies. Although some studies have indicated an association between the TP53 Arg/Arg variant and an increased risk for prostate cancer, other studies have shown a positive correlation between the TP53 Pro/Pro genotype instead. Therefore, to clarify if this polymorphism is associated with an increased risk of prostate cancer in Iranian men, we conducted a case-control study of 40 sporadic prostate cancer patients and 80 benign prostate hyperplasia cases. Methods The TP53 codon 72 was genotyped using an allele specific PCR. Results A significant association between the TP53 codon 72 genotype and prostate cancer risk was found (OR = 6.8, 95% CI = [1.8-25.1], P = 0.005). However, the results of this study did not support an association between age, the Gleason score nor TP53 genotype at codon 72 in prostate cancer patients. Conclusions TP53 codon 72 polymorphism may have a great impact in the development of prostate cancer. PMID:26005655

  1. SYNONYMOUS CODONS DIRECT CO-TRANSLATIONAL FOLDING TOWARDS DIFFERENT PROTEIN CONFORMATIONS

    PubMed Central

    Mittelstaet, Joerg; Kutz, Felicitas; Schwalbe, Harald; Rodnina, Marina V.; Komar, Anton A.

    2016-01-01

    SUMMARY In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. Here we show that synonymous codon variants in the gene encoding gamma-B crystallin, a mammalian eye lens protein, modulate the rates of translation and co-translational folding of protein domains monitored in real time by Förster resonance energy transfer and fluorescence intensity changes. Gamma-B crystallins produced from mRNAs with changed codon bias have the same amino acid sequence, but attain different conformations as indicated by altered in vivo stability and in vitro protease resistance. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Thus, synonymous codons provide a secondary code for protein folding in the cell. PMID:26849192

  2. Reassignment of a rare sense codon to a non-canonical amino acid in Escherichia coli

    PubMed Central

    Mukai, Takahito; Yamaguchi, Atsushi; Ohtake, Kazumasa; Takahashi, Mihoko; Hayashi, Akiko; Iraha, Fumie; Kira, Satoshi; Yanagisawa, Tatsuo; Yokoyama, Shigeyuki; Hoshi, Hiroko; Kobayashi, Takatsugu; Sakamoto, Kensaku

    2015-01-01

    The immutability of the genetic code has been challenged with the successful reassignment of the UAG stop codon to non-natural amino acids in Escherichia coli. In the present study, we demonstrated the in vivo reassignment of the AGG sense codon from arginine to l-homoarginine. As the first step, we engineered a novel variant of the archaeal pyrrolysyl-tRNA synthetase (PylRS) able to recognize l-homoarginine and l-N6-(1-iminoethyl)lysine (l-NIL). When this PylRS variant or HarRS was expressed in E. coli, together with the AGG-reading tRNAPylCCU molecule, these arginine analogs were efficiently incorporated into proteins in response to AGG. Next, some or all of the AGG codons in the essential genes were eliminated by their synonymous replacements with other arginine codons, whereas the majority of the AGG codons remained in the genome. The bacterial host's ability to translate AGG into arginine was then restricted in a temperature-dependent manner. The temperature sensitivity caused by this restriction was rescued by the translation of AGG to l-homoarginine or l-NIL. The assignment of AGG to l-homoarginine in the cells was confirmed by mass spectrometric analyses. The results showed the feasibility of breaking the degeneracy of sense codons to enhance the amino-acid diversity in the genetic code. PMID:26240376

  3. Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

    PubMed Central

    Bali, Vedrana; Bebok, Zsuzsanna

    2015-01-01

    Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

  4. Reduced Dosage of Genes Encoding Ribosomal Protein S18 Suppresses a Mitochondrial Initiation Codon Mutation in Saccharomyces Cerevisiae

    PubMed Central

    Folley, L. S.; Fox, T. D.

    1994-01-01

    A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code the essential cytoplasmic small subunit ribosomal protein termed S18 in yeast. The two S18 genes differ only by 21 silent substitutions in their exons; both are interrupted by a single intron after the 15th codon. Yeast S18 is homologous to the human S11 (70% identical) and the Escherichia coli S17 (35% identical) ribosomal proteins. This highly conserved family of ribosomal proteins has been implicated in maintenance of translational accuracy and is essential for assembly of the small ribosomal subunit. Characterization of the original rps18a-1 missense mutant and rps18aΔ and rps18bΔ null mutants revealed that levels of suppression, cold sensitivity and paromomycin sensitivity all varied directly with a limitation of small ribosomal subunits. The rps18a-1 mutant was most affected, followed by rps18aΔ then rps18bΔ. Mitochondrial mutations that decreased COX3 expression without altering the initiation codon were not suppressed. This allele specificity implicates mitochondrial translation in the mechanism of suppression. We could not detect an epitope-tagged variant of S18 in mitochondria. Thus, it appears that suppression of the mitochondrial translation initiation defect is caused indirectly by reduced levels of cytoplasmic small ribosomal subunits, leading to changes in either cytoplasmic translational accuracy or the relative levels of cytoplasmic translation products. PMID:8070651

  5. Age-related changes in adaptive macronutrient intake in swimming male and female Lou rats.

    PubMed

    Boghossian, S; Veyrat-Durebex, C; Alliot, J

    2000-05-01

    To evaluate the age-related changes in capacity to adjust the nutrient intake to needs, self-selecting male and female Lou/C/jall rats of 4, 6, 12, 16 and 23 months of age were submitted to a swimming exercise. They were given 6 consecutive days of moderate intensity training (3 x 15 minutes per day). Exercise and postexercise periods were compared with results from the pretraining period. During swimming, a body weight loss and a decrease in both caloric intake and fat selection were observed. This effect was more marked in older groups compared to 4 month-old groups. An increase in protein intake was observed in females, specially in older groups, whereas no effect was seen in males. The ability to increase caloric ingestion and regain weight during the postexercise period decreased with advancing age and was better in females than in males. We also showed an age-related effect on the recovery of initial nutrient intake rate that was more pronounced and more precocious for males. Moreover, males tended to decrease their protein intake, whereas females significantly increased it. The present findings suggest a decrease of capacity of adjusting feeding behavior to metabolic needs in aged rats, may be due to a deterioration of the central control of food intake.

  6. Adaptive user interfaces for relating high-level concepts to low-level photographic parameters

    NASA Astrophysics Data System (ADS)

    Scott, Edward; Madhawa Silva, Pubudu; Pardo, Bryan; Pappas, Thrasyvoulos N.

    2011-03-01

    Common controls for photographic editing can be difficult to use and have a significant learning curve. Often, a user does not know a direct mapping from a high-level concept (such as "soft") to the available parameters or controls. In addition, many concepts are subjective in nature, and the appropriate mapping may vary from user to user. To overcome these problems, we propose a system that can quickly learn a mapping from a high-level subjective concept onto low- level image controls using machine learning techniques. To learn such a concept, the system shows the user a series of training images that are generated by modifying a seed image along different dimensions (e.g., color, sharpness), and collects the user ratings of how well each training image matches the concept. Since it is known precisely how each modified example is different from the original, the system can determine the correlation between the user ratings and the image parameters to generate a controller tailored to the concept for the given user. The end result - a personalized image controller - is applicable to a variety of concepts. We have demonstrated the utility of this approach to relate low-level parameters, such as color balance and sharpness, to simple concepts, such as "lightness" and "crispness," as well as more complex and subjective concepts, such as "pleasantness." We have also applied the proposed approach to relate subband statistics (variance) to perceived roughness of visual textures (from the CUReT database).

  7. Adaptation of plants to altered shoot orientation relative to the gravity vector.

    PubMed

    Smolyanina, S O; Berkovich, Yu A; Ivanov, V B

    2004-07-01

    Wheat Triticum aestivum L., carrots Daucus carota L., Chinese cabbage Brassica pekinensis Rupr., and African marigold Tagetes patula L. were grown at natural and inverted orientation in the Earth gravitational field. Light vector was set unidirectional or opposite directional relative to the gravity vector. Shoot orientation relative to the gravity vector was set natural or invert. Plants grew in the special pots furnished with plane or cylindrical hydrophilic porous membranes. The membrane allowed to stabilize a water potential in the root zone at the fixed level. Seeds were put into a fiber ion-exchange artificial soil overlaying horizontal hydrophilic plates of porous titanium or anchored to porous metal-ceramic tubes. Plants grew at the PPF level 550 +/- 20 micromoles/(m2 s) during 24-hr lighting and at the water potential level at the membrane surface (-1.00) +/- 0.08 kPa. Normal plants were obtained both at the natural and at the inverse shoot orientation in the all experiments. The wheat plants were yielded healthy germinating seeds no matter plant orientation. In the inverse orientation, no negative influence for plant biomass accruing was marked, but the increasing of shoot to root mass ratio was considerable. However carrot root crop mass decreasing was not revealed in the inverse orientation. The results demonstrated substantial dependence of morphological and physiological characteristics of higher plants on the gravity factor.

  8. How adaptable is the hydraulic system of European beech in the face of climate change-related precipitation reduction?

    PubMed

    Schuldt, Bernhard; Knutzen, Florian; Delzon, Sylvain; Jansen, Steven; Müller-Haubold, Hilmar; Burlett, Régis; Clough, Yann; Leuschner, Christoph

    2016-04-01

    Climate warming will increase the drought exposure of many forests world-wide. It is not well understood how trees adapt their hydraulic architecture to a long-term decrease in water availability. We examined 23 traits characterizing the hydraulic architecture and growth rate of branches and the dependent foliage of mature European beech (Fagus sylvatica) trees along a precipitation gradient (855-594 mm yr(-1) ) on uniform soil. A main goal was to identify traits that are associated with xylem efficiency, safety and growth. Our data demonstrate for the first time a linear increase in embolism resistance with climatic aridity (by 10%) across populations within a species. Simultaneously, vessel diameter declined by 7% and pit membrane thickness (Tm ) increased by 15%. Although specific conductivity did not change, leaf-specific conductivity declined by 40% with decreasing precipitation. Of eight plant traits commonly associated with embolism resistance, only vessel density in combination with pathway redundancy and Tm were related. We did not confirm the widely assumed trade-off between xylem safety and efficiency but obtained evidence in support of a positive relationship between hydraulic efficiency and growth. We conclude that the branch hydraulic system of beech has a distinct adaptive potential to respond to a precipitation reduction as a result of the environmental control of embolism resistance.

  9. The burgeoning field of transdisciplinary adaptation research in Quebec (1998–): a climate change-related public health narrative

    PubMed Central

    Gosselin, Pierre; Bélanger, Diane; Lapaige, Véronique; Labbé, Yolaine

    2011-01-01

    ) in which the issues are successively explored, understood, and conceptualized for all of Quebec, and (3) problem transformation (2006–2009), which discusses major interactions among the stakeholders and the presentation of an Action Plan by a central actor, the Quebec government, in alliance with other stakeholders. In conclusion, we underline the importance, in the current context, of providing for a sustained transdisciplinary adaptation to climatic change. This paper should be helpful for (1) public health professionals confronted with establishing a transdisciplinary approach to a real-world problem other than climate change, (2) professionals in other sectors (such as public safety, built environment) confronted with climate change, who wish to implement transdisciplinary adaptive interventions and/or research, and (3) knowledge users (public and private actors; nongovernment organizations; citizens) from elsewhere in multi-contexts/environments/sectors who wish to promote complex collaborations (with us or not), collective leadership, and “transfrontier knowledge-to-action” for implementing climate change-related adaptation measures. PMID:21966228

  10. Development of a real-time polymerase chain reaction assay for single nucleotide polymorphism genotyping codons 136, 154, and 171 of the prnp gene and application to Brazilian sheep herds.

    PubMed

    de Andrade, Caroline P; de Almeida, Laura L; de Castro, Luiza A; Driemeier, David; da Silva, Sérgio C

    2013-01-01

    Scrapie is a transmissible spongiform encephalopathy of sheep and goats and is associated with the deposition of an abnormal isoform of prion protein (PrP(sc)). This isoform presents an altered conformation that leads to its aggregation in the host's central nervous and lymphoreticular systems. A predisposition to the prion-agent infection can be influenced by specific genotypes that are related to polymorphisms in the ovine prnp gene. The most characterized polymorphisms occur at codons 136, 154, and 171, with genotype VRQ being the most susceptible and ARR the most resistant. In the current study, a real-time quantitative polymerase chain reaction (qPCR) technique based on allele-specific TaqMan probes was developed to identify single nucleotide polymorphisms in the prnp gene from Brazilian herds. Specific primers and TaqMan probes were designed for all 3 codons of interest. Samples from a total of 142 animals were analyzed by qPCR, followed by DNA sequencing of the amplicons. All of the genotypes determined by qPCR were in agreement with the data determined by DNA sequencing. In all 3 of the analyzed breeds, the majority of the animals were AA homozygous for the 136 codon. The most frequent genotype for codon 154 was RR, and genotypes QQ and QR were the most frequent for codon 171. The results are discussed in relation to establishing scrapie control measures and breeding programs for Brazilian herds.

  11. Adaptive Function in Preschoolers in Relation to Developmental Delay and Diagnosis of Autism Spectrum Disorders: Insights from a Clinical Sample

    ERIC Educational Resources Information Center

    Milne, Susan L.; McDonald, Jenny L.; Comino, Elizabeth J.

    2013-01-01

    This study aims to explore the relationship between developmental ability, autism and adaptive skills in preschoolers. Adaptive function was assessed in 152 preschoolers with autism, with and without developmental delay, and without autism, with and without developmental delay. Their overall adaptive function, measured by the general adaptive…

  12. Adaptive extraction of emotion-related EEG segments using multidimensional directed information in time-frequency domain.

    PubMed

    Petrantonakis, Panagiotis C; Hadjileontiadis, Leontios J

    2010-01-01

    Emotion discrimination from electroencephalogram (EEG) has gained attention the last decade as a user-friendly and effective approach to EEG-based emotion recognition (EEG-ER) systems. Nevertheless, challenging issues regarding the emotion elicitation procedure, especially its effectiveness, raise. In this work, a novel method, which not only evaluates the degree of emotion elicitation but localizes the emotion information in the time-frequency domain, as well, is proposed. The latter, incorporates multidimensional directed information at the time-frequency EEG representation, extracted using empirical mode decomposition, and introduces an asymmetry index for adaptive emotion-related EEG segment selection. Experimental results derived from 16 subjects visually stimulated with pictures from the valence/arousal space drawn from the International Affective Picture System database, justify the effectiveness of the proposed approach and its potential contribution to the enhancement of EEG-ER systems.

  13. Morphology and locomotor adaptations of the bovid femur in relation to habitat.

    PubMed

    Kappelman, J

    1988-10-01

    Extant bovids inhabit a wide diversity of environments that range from forest to savanna and display locomotor patterns that are habitat specific. I report here on an investigation of the linkage between these locomotor patterns and habitat based on a study of the morphology of the bovid femur. Femoral head shape, shaft dimensions, and knee structure are examined and support a statistically significant separation of the different morphological complexes present in bovids from forest, broken cover, and savanna habitats. Morphological differences are primarily related to locomotor patterns as reflected in the degree of cursoriality displayed by bovids in different habitats. Cursorial bovids from savanna environments have laterally expanded femoral heads that act to limit the degree of abduction and axial rotation at the hip, and elliptically shaped distal femora that increase the moment arm of the extensor muscles that cross the knee. Forest bovids have spherically shaped femoral heads. This morphology permits a much higher degree of abduction and axial rotation at the hip and appears to provide greater maneuverability in a vegetationally complex habitat. Bovids living in broken cover environments that fall between the extremes of closed canopy forest and savanna display an intermediate set of femoral characters. This approach to the relationship between habitat and locomotion offers a potentially powerful means with which to examine the interplay between structural form and function in bovid evolution.

  14. Physiological and morphological adaptations in relation to water use efficiency in Mediterranean accessions of Solanum lycopersicum.

    PubMed

    Galmés, Jeroni; Conesa, Miquel Àngel; Ochogavía, Joan Manuel; Perdomo, Juan Alejandro; Francis, David M; Ribas-Carbó, Miquel; Savé, Robert; Flexas, Jaume; Medrano, Hipólito; Cifre, Josep

    2011-02-01

    The physiological traits underlying the apparent drought resistance of 'Tomàtiga de Ramellet' (TR) cultivars, a population of Mediterranean tomato cultivars with delayed fruit deterioration (DFD) phenotype and typically grown under non-irrigation conditions, are evaluated. Eight different tomato accessions were selected and included six TR accessions, one Mediterranean non-TR accession (NTR(M)) and a processing cultivar (NTR(O)). Among the TR accessions two leaf morphology types, normal divided leaves and potato-leaf, were selected. Plants were field grown under well-watered (WW) and water-stressed (WS) treatments, with 30 and 10% of soil water capacity, respectively. Accessions were clustered according to the leaf type and TR phenotype under WW and WS, respectively. Correlation among parameters under the different water treatments suggested that potential improvements in the intrinsic water-use efficiency (A(N)/g(s)) are possible without negative impacts on yield. Under WS TR accessions displayed higher A(N)/g(s), which was not due to differences in Rubisco-related parameters, but correlated with the ratio between the leaf mesophyll and stomatal conductances (g(m)/g(s)). The results confirm the existence of differential traits in the response to drought stress in Mediterranean accessions of tomato, and demonstrate that increases in the g(m)/g(s) ratio would allow improvements in A(N)/g(s) in horticultural crops.

  15. Increased expression of estrogen-related receptor β during adaptation of adult cardiomyocytes to sustained hypoxia

    PubMed Central

    Cunningham, Kathryn F; Beeson, Gyda C; Beeson, Craig C; McDermott, Paul J

    2016-01-01

    Estrogen-related Receptors (ERR) are members of the steroid hormone receptor superfamily of transcription factors that regulate expression of genes required for energy metabolism including mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. While ERRα and EPPγ isoforms are known to share a wide array of target genes in the adult myocardium, the function of ERRβ has not been characterized in cardiomyocytes. The purpose of this study was to determine the role of ERRβ in regulating energy metabolism in adult cardiomyocytes in primary culture. Adult feline cardiomyocytes were electrically stimulated to contract in either hypoxia (0.5% O2) or normoxia (21% O2). As compared to baseline values measured in normoxia, ERRβ mRNA levels increased significantly after 8 hours of hypoxia and remained elevated over 24 h. Conversely, ERRβ mRNA decreased to normoxic levels after 4 hours of reoxygenation. Hypoxia increased expression of the α and β isoforms of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 (PGC-1) mRNA by 6-fold and 3-fold, respectively. Knockdown of ERRβ expression via adenoviral-mediated delivery of ERRβ shRNA blocked hypoxia-induced increases in PGC-1β mRNA, but not PGC-1α mRNA. Loss of ERRβ had no effect on mtDNA content as measured after 24 h of hypoxia. To determine whether loss of ERRβ affected mitochondrial function, oxygen consumption rates (OCR) were measured in contracting versus quiescent cardiomyocytes in normoxia. OCR was significantly lower in contracting cardiomyocytes expressing ERRβ shRNA than scrambled shRNA controls. Maximal OCR also was reduced by ERRβ knockdown. In conclusion: 1) hypoxia increases in ERRβ mRNA expression in contracting cardiomyocytes; 2) ERRβ is required for induction of the PGC-1β isoform in response to hypoxia; 3) ERRβ expression is required to sustain OCR in normoxic conditions. PMID:27335690

  16. Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

    PubMed Central

    Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias

    2016-01-01

    Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1–67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28–79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17–32 yr, 3rd quartile: 33–48 yr, and 4th quartile: 49–64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. PMID:26747496

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

    PubMed Central

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

    2014-01-01

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

  18. Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

    PubMed Central

    Kwon, Inchan; Choi, Eun Sil

    2016-01-01

    Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

  19. Variability of hair coat and skin traits as related to adaptation in Criollo Limonero cattle.

    PubMed

    Landaeta-Hernández, Antonio; Zambrano-Nava, Sunny; Hernández-Fonseca, Juan P; Godoy, Rosario; Calles, Marcos; Iragorri, José L; Añez, Lauderys; Polanco, Miguel; Montero-Urdaneta, Merilio; Olson, Tim

    2011-03-01

    The variation in hair coat and skin histology traits of Criollo Limonero cattle was analyzed using 213 Criollo Limonero females. Skin biopsies were obtained from slick-haired (N=16) and normal-haired (N=14) animals. Measured traits included hair length (HL), color coat (CC), number of hair follicles per square centimeter (NHF), sweat glands per square centimeter (NSG), sweat glands size (SGS), sebaceous glands per square centimeter (NSBG), blood vessels per square centimeter (NBV), and thickness of epidermis (TE). Hair length differed (P<0.001) between slick- and normal-haired animals (4.9 ± 0.12 vs 10.9 ± 0.20, respectively). Differences (P<0.01) in CC (Bayo = 144/67.6% vs Red = 69/32.4%) and HL (slick-haired = 199/93.4% vs normal-haired = 14/6.5%) were found. Distribution of slick- and normal-haired animals differed (P<0.01) between bayo-coated and red-coated (139/62.2% vs 9/4.2%; respectively). Most (P<0.05) red-coated animals belonged to a single family. No differences (P>0.05) were found between slick-haired and normal-haired animals in NHF (637 ± 164 vs 587 ± 144, respectively), NSG (556 ± 134 vs 481 ± 118, respectively), NSBG (408 ± 87 vs 366 ± 77, respectively), NBV (1628 ± 393 vs 1541 ± 346, respectively), and TE (1.24 ± 0.14 vs 1.32 ± 0.12, respectively). However, SGS was greater (P<0.01) in slick-haired than normal-haired animals. In conclusion, Criollo Limonero cattle are predominantly bayo-coated, slick-haired, with a reduced number of hair follicles relative to Zebu cattle, sweat and sebaceous glands in proportion to hair follicle numbers, and with a high blood flow irrigating the skin. There is a sub-group of red-coated animals with yellow or cream skin, thicker epidermis, and with a higher frequency of normal-haired animals. It appears that the slick hair gene has been favored by natural selection in this breed.

  20. Back to the wilds: tapping evolutionary adaptations for resilient crops through systematic hybridization with crop wild relatives.

    PubMed

    Warschefsky, Emily; Penmetsa, R Varma; Cook, Douglas R; von Wettberg, Eric J B

    2014-10-01

    The genetic diversity of our crop plants has been substantially reduced during the process of domestication and breeding. This reduction in diversity necessarily constrains our ability to expand a crop's range of cultivation into environments that are more extreme than those in which it was domesticated, including into "sustainable" agricultural systems with reduced inputs of pesticides, water, and fertilizers. Conversely, the wild progenitors of crop plants typically possess high levels of genetic diversity, which underlie an expanded (relative to domesticates) range of adaptive traits that may be of agricultural relevance, including resistance to pests and pathogens, tolerance to abiotic extremes, and reduced dependence on inputs. Despite their clear potential for crop improvement, wild relatives have rarely been used systematically for crop improvement, and in no cases, have full sets of wild diversity been introgressed into a crop. Instead, most breeding efforts have focused on specific traits and dealt with wild species in a limited and typically ad hoc manner. Although expedient, this approach misses the opportunity to test a large suite of traits and deploy the full potential of crop wild relatives in breeding for the looming challenges of the 21st century. Here we review examples of hybridization in several species, both intentionally produced and naturally occurring, to illustrate the gains that are possible. We start with naturally occurring hybrids, and then examine a range of examples of hybridization in agricultural settings.

  1. Translation Regulation of the Glutamyl-prolyl-tRNA Synthetase Gene EPRS through Bypass of Upstream Open Reading Frames with Noncanonical Initiation Codons.

    PubMed

    Young, Sara K; Baird, Thomas D; Wek, Ronald C

    2016-05-13

    In the integrated stress response, phosphorylation of eIF2α (eIF2α-P) reduces protein synthesis while concomitantly promoting preferential translation of specific transcripts associated with stress adaptation. Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2α-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and expression of the EPRS coding region. Our findings reveal that translation of two inhibitory uORFs encoded by noncanonical CUG and UUG initiation codons in the EPRS mRNA 5'-leader serve to dampen levels of translation initiation at the EPRS coding region. By a mechanism suggested to involve increased translation initiation stringency during stress-induced eIF2α-P, we observed facilitated ribosome bypass of these uORFs, allowing for increased translation of the EPRS coding region. Importantly, EPRS protein expression is enhanced through this preferential translation mechanism in response to multiple known activators of eIF2α-P and likely serves to facilitate stress adaptation in response to a variety of cellular stresses. The rules presented here for the regulated ribosome bypass of noncanonical initiation codons in the EPRS 5'-leader add complexity into the nature of uORF-mediated translation control mechanisms during eIF2α-P and additionally illustrate the roles that previously unexamined uORFs with noncanonical initiation codons can play in modulating gene expression.

  2. Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2

    PubMed Central

    Imamura, Masataka; Higashi, Kyohei; Yamaguchi, Katsutoshi; Asakura, Kiryu; Furihata, Tomomi; Terui, Yusuke; Satake, Toshihiko; Maegawa, Jiro; Yasumura, Kazunori; Ibuki, Ai; Akase, Tomoko; Nishimura, Kazuhiro; Kashiwagi, Keiko; Linhardt, Robert J.; Igarashi, Kazuei; Toida, Toshihiko

    2016-01-01

    Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5′-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines. PMID:27650265

  3. Identification of codon-specific serine to asparagine mistranslation in recombinant monoclonal antibodies by high-resolution mass spectrometry.

    PubMed

    Yu, X Christopher; Borisov, Oleg V; Alvarez, Melissa; Michels, David A; Wang, Yajun Jennifer; Ling, Victor

    2009-11-15

    Translation errors in protein biosynthesis may result in low level amino acid misincorporation and contribute to product heterogeneity of recombinant protein therapeutics. We report the use of peptide map analysis by reversed-phase high-performance liquid chromatography and high-resolution mass spectrometry to detect and identify mistranslation events in recombinant monoclonal antibodies expressed in mammalian cell lines including Chinese hamster ovary (CHO) cells. Misincorporation of an asparagine residue at multiple serine positions was detected as earlier-eluting peptides with masses 27.01 Da higher than expected. The exact positions at which misincorporation occurred were identified by tandem mass spectrometry of the asparagine-containing variant peptides. The identified asparagine misincorporation sites correlated with the use of codon AGC but with none of the other five serine codons. The relative levels of misincorporation ranged from 0.01%-0.2% among multiple serine positions detected across three different antibodies by targeted analysis of expected and variant peptides. The low levels of misincorporation are consistent with published predictions for in vivo translation error rates. Our results demonstrate that state-of-the-art mass spectrometry with a combination of high sensitivity, accuracy, and dynamic range provides a new ability to discover and characterize low level protein variants that arise from mistranslation events.

  4. Modeling the effect of codon translation rates on co-translational protein folding mechanisms of arbitrary complexity

    NASA Astrophysics Data System (ADS)

    Caniparoli, Luca; O'Brien, Edward P.

    2015-04-01

    In a cell, the folding of a protein molecule into tertiary structure can begin while it is synthesized by the ribosome. The rate at which individual amino acids are incorporated into the elongating nascent chain has been shown to affect the likelihood that proteins will populate their folded state, indicating that co-translational protein folding is a far from equilibrium process. Developing a theoretical framework to accurately describe this process is, therefore, crucial for advancing our understanding of how proteins acquire their functional conformation in living cells. Current state-of-the-art computational approaches, such as molecular dynamics simulations, are very demanding in terms of the required computer resources, making the simulation of co-translational protein folding difficult. Here, we overcome this limitation by introducing an efficient approach that predicts the effects that variable codon translation rates have on co-translational folding pathways. Our approach is based on Markov chains. By using as an input a relatively small number of molecular dynamics simulations, it allows for the computation of the probability that a nascent protein is in any state as a function of the translation rate of individual codons along a mRNA's open reading frame. Due to its computational efficiency and favorable scalability with the complexity of the folding mechanism, this approach could enable proteome-wide computational studies of the influence of translation dynamics on co-translational folding.

  5. RCPdb: An evolutionary classification and codon usage database for repeat-containing proteins

    PubMed Central

    Faux, Noel G.; Huttley, Gavin A.; Mahmood, Khalid; Webb, Geoffrey I.; Garcia de la Banda, Maria; Whisstock, James C.

    2007-01-01

    Over 3% of human proteins contain single amino acid repeats (repeat-containing proteins, RCPs). Many repeats (homopeptides) localize to important proteins involved in transcription, and the expansion of certain repeats, in particular poly-Q and poly-A tracts, can also lead to the development of neurological diseases. Previous studies have suggested that the homopeptide makeup is a result of the presence of G+C-rich tracts in the encoding genes and that expansion occurs via replication slippage. Here, we have performed a large-scale genomic analysis of the variation of the genes encoding RCPs in 13 species and present these data in an online database (http://repeats.med.monash.edu.au/genetic_analysis/). This resource allows rapid comparison and analysis of RCPs, homopeptides, and their underlying genetic tracts across the eukaryotic species considered. We report three major findings. First, there is a bias for a small subset of codons being reiterated within homopeptides, and there is no G+C or A+T bias relative to the organism’s transcriptome. Second, single base pair transversions from the homocodon are unusually common and may represent a mechanism of reducing the rate of homopeptide mutations. Third, homopeptides that are conserved across different species lie within regions that are under stronger purifying selection in contrast to nonconserved homopeptides. PMID:17567984

  6. Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element.

    PubMed

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

    2011-08-01

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

  7. Sustainability Impact Assessment of two forest-based bioenergy production systems related to mitigation and adaption to Climate Change

    NASA Astrophysics Data System (ADS)

    Gartzia-Bengoetxea, Nahia; Arias-González, Ander; Tuomasjukka, Diana

    2016-04-01

    New forest management strategies are necessary to resist and adapt to Climate Change (CC) and to maintain ecosystem functions such as forest productivity, water storage and biomass production. The increased use of forest-based biomass for energy generation as well as the application of combustion or pyrolysis co-products such as ash or biochar back into forest soils is being suggested as a CC mitigation and adaptation strategy while trying to fulfil the targets of both: (i) Europe 2020 growth strategy in relation to CC and energy sustainability and (ii) EU Action Plan for the Circular Economy. The energy stored in harvested biomass can be released through combustion and used for energy generation to enable national energy security (reduced oil dependence) and the substitution of fossil fuel by renewable biomass can decrease the emission of greenhouse gases.In the end, the wood-ash produced in the process can return to the forest soil to replace the nutrients exported by harvesting. Another way to use biomass in this green circular framework is to pyrolyse it. Pyrolysis of the biomass produce a carbon-rich product (biochar) that can increase carbon sequestration in the soils and liquid and gas co-products of biomass pyrolysis can be used for energy generation or other fuel use thereby offsetting fossil fuel consumption and so avoiding greenhouse gas emissions. Both biomass based energy systems differ in the amount of energy produced, in the co-product (biochar or wood ash) returned to the field, and in societal impacts they have. The Tool for Sustainability Impact Assessment (ToSIA) was used for modelling both energy production systems. ToSIA integrates several different methods, and allows a quantification and objective comparison of economic, environmental and social impacts in a sustainability impact assessment for different decision alternatives/scenarios. We will interpret the results in order to support the bioenergy planning in temperate forests under the

  8. Climate adaptation

    NASA Astrophysics Data System (ADS)

    Kinzig, Ann P.

    2015-03-01

    This paper is intended as a brief introduction to climate adaptation in a conference devoted otherwise to the physics of sustainable energy. Whereas mitigation involves measures to reduce the probability of a potential event, such as climate change, adaptation refers to actions that lessen the impact of climate change. Mitigation and adaptation differ in other ways as well. Adaptation does not necessarily have to be implemented immediately to be effective; it only needs to be in place before the threat arrives. Also, adaptation does not necessarily require global, coordinated action; many effective adaptation actions can be local. Some urban communities, because of land-use change and the urban heat-island effect, currently face changes similar to some expected under climate change, such as changes in water availability, heat-related morbidity, or changes in disease patterns. Concern over those impacts might motivate the implementation of measures that would also help in climate adaptation, despite skepticism among some policy makers about anthropogenic global warming. Studies of ancient civilizations in the southwestern US lends some insight into factors that may or may not be important to successful adaptation.

  9. Water relations and gas exchange of fan bryophytes and their adaptations to microhabitats in an Asian subtropical montane cloud forest.

    PubMed

    Song, Liang; Zhang, Yong-Jiang; Chen, Xi; Li, Su; Lu, Hua-Zheng; Wu, Chuan-Sheng; Tan, Zheng-Hong; Liu, Wen-Yao; Shi, Xian-Meng

    2015-07-01

    Fan life forms are bryophytes with shoots rising from vertical substratum that branch repeatedly in the horizontal plane to form flattened photosynthetic surfaces, which are well suited for intercepting water from moving air. However, detailed water relations, gas exchange characteristics of fan bryophytes and their adaptations to particular microhabitats remain poorly understood. In this study, we measured and analyzed microclimatic data, as well as water release curves, pressure-volume relationships and photosynthetic water and light response curves for three common fan bryophytes in an Asian subtropical montane cloud forest (SMCF). Results demonstrate high relative humidity but low light levels and temperatures in the understory, and a strong effect of fog on water availability for bryophytes in the SMCF. The facts that fan bryophytes in dry air lose most of their free water within 1 h, and a strong dependence of net photosynthesis rates on water content, imply that the transition from a hydrated, photosynthetically active state to a dry, inactive state is rapid. In addition, fan bryophytes developed relatively high cell wall elasticity and the osmoregulatory capacity to tolerate desiccation. These fan bryophytes had low light saturation and compensation point of photosynthesis, indicating shade tolerance. It is likely that fan bryophytes can flourish on tree trunks in the SMCF because of substantial annual precipitation, average relative humidity, and frequent and persistent fog, which can provide continual water sources for them to intercept. Nevertheless, the low water retention capacity and strong dependence of net photosynthesis on water content of fan bryophytes indicate a high risk of unbalanced carbon budget if the frequency and severity of drought increase in the future as predicted.

  10. Age-related changes in primary somatosensory cortex of rats: evidence for parallel degenerative and plastic-adaptive processes.

    PubMed

    Godde, Ben; Berkefeld, Thomas; David-Jürgens, Marianne; Dinse, Hubert R

    2002-11-01

    Aged rats show a characteristic decline of the sensorimotor state, most strikingly expressed in an impairment of the hindlimbs leading to significantly reduced sensory stimulation on the hindpaw. We review recent studies using optical imaging and electrophysiological recordings to investigate the effects of aging on somatosensory cortex and to identify age-related changes in terms of degeneration or plastic adaptation. For the cortical hindpaw representation, reduction of map size, receptive field enlargement and reduced response strength were described. None of these changes were reported in the forepaw representation in the same individual, however, in both the fore-and hindpaw representations response latencies and cerebral blood flow were affected. Changes of latencies and blood flow are best explained by degeneration, but the regional and specific changes of maps, receptive fields and response strength by plastic phenomena arising from the reduced sensory inputs. While the degenerative changes are not modifiable by enriched environmental conditions or application of Ca(2+) blocker, the plastic changes were fully reversible under these conditions. We discuss the implications of these findings for cognitive functions at old age and possible treatments of age-related changes in human subjects.

  11. p53 codon 72 polymorphism and breast cancer risk: A meta-analysis

    PubMed Central

    HOU, JING; JIANG, YUAN; TANG, WENRU; JIA, SHUTING

    2013-01-01

    p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931–1.11, P=0.722). The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required. PMID:23737888

  12. Non-universal decoding of the leucine codon CUG in several Candida species.

    PubMed Central

    Ohama, T; Suzuki, T; Mori, M; Osawa, S; Ueda, T; Watanabe, K; Nakase, T

    1993-01-01

    It has been reported that CUG, a universal leucine codon, is read as serine in an asporogenic yeast, Candida cylindracea. The distribution of this non-universal genetic code in various yeast species was studied using an in vitro translation assay system with a synthetic messenger RNA containing CUG codons in-frame. It was found that CUG is used as a serine codon in six out of the fourteen species examined, while it is used for leucine in the remaining eight. The tRNA species responsible for the translation of codon CUG as serine was detected in all the six species in which CUG is translated as serine. The grouping according to the CUG codon assignments in these yeast species shows a good correlation with physiological classification by the chain lengths of the isoprenoid moiety of ubiquinone and the cell-wall sugar contained in the yeasts. The six Candida species examined in which CUG is used as serine belong to one distinct group in Hemiascomycetes. PMID:8371978

  13. Analysis of Adaptive Evolution in Lyssavirus Genomes Reveals Pervasive Diversifying Selection during Species Diversification

    PubMed Central

    Voloch, Carolina M.; Capellão, Renata T.; Mello, Beatriz; Schrago, Carlos G.

    2014-01-01

    Lyssavirus is a diverse genus of viruses that infect a variety of mammalian hosts, typically causing encephalitis. The evolution of this lineage, particularly the rabies virus, has been a focus of research because of the extensive occurrence of cross-species transmission, and the distinctive geographical patterns present throughout the diversification of these viruses. Although numerous studies have examined pattern-related questions concerning Lyssavirus evolution, analyses of the evolutionary processes acting on Lyssavirus diversification are scarce. To clarify the relevance of positive natural selection in Lyssavirus diversification, we conducted a comprehensive scan for episodic diversifying selection across all lineages and codon sites of the five coding regions in lyssavirus genomes. Although the genomes of these viruses are generally conserved, the glycoprotein (G), RNA-dependent RNA polymerase (L) and polymerase (P) genes were frequently targets of adaptive evolution during the diversification of the genus. Adaptive evolution is particularly manifest in the glycoprotein gene, which was inferred to have experienced the highest density of positively selected codon sites along branches. Substitutions in the L gene were found to be associated with the early diversification of phylogroups. A comparison between the number of positively selected sites inferred along the branches of RABV population branches and Lyssavirus intespecies branches suggested that the occurrence of positive selection was similar on the five coding regions of the genome in both groups. PMID:25415197

  14. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

  15. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus

    PubMed Central

    2011-01-01

    Background Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Conclusions Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was occurring at antigen binding

  16. Age-Related Adaptation of Bone-PDL-Tooth Complex: Rattus-Norvegicus as a Model System

    PubMed Central

    Leong, Narita L.; Hurng, Jonathan M.; Djomehri, Sabra I.; Gansky, Stuart A.; Ryder, Mark I.; Ho, Sunita P.

    2012-01-01

    Functional loads on an organ induce tissue adaptations by converting mechanical energy into chemical energy at a cell-level. The transducing capacity of cells alters physico-chemical properties of tissues, developing a positive feedback commonly recognized as the form-function relationship. In this study, organ and tissue adaptations were mapped in the bone-tooth complex by identifying and correlating biomolecular expressions to physico-chemical properties in rats from 1.5 to 15 months. However, future research using hard and soft chow over relevant age groups would decouple the function related effects from aging affects. Progressive curvature in the distal root with increased root resorption was observed using micro X-ray computed tomography. Resorption was correlated to the increased activity of multinucleated osteoclasts on the distal side of the molars until 6 months using tartrate resistant acid phosphatase (TRAP). Interestingly, mononucleated TRAP positive cells within PDL vasculature were observed in older rats. Higher levels of glycosaminoglycans were identified at PDL-bone and PDL-cementum entheses using alcian blue stain. Decreasing biochemical gradients from coronal to apical zones, specifically biomolecules that can induce osteogenic (biglycan) and fibrogenic (fibromodulin, decorin) phenotypes, and PDL-specific negative regulator of mineralization (asporin) were observed using immunohistochemistry. Heterogeneous distribution of Ca and P in alveolar bone, and relatively lower contents at the entheses, were observed using energy dispersive X-ray analysis. No correlation between age and microhardness of alveolar bone (0.7±0.1 to 0.9±0.2 GPa) and cementum (0.6±0.1 to 0.8±0.3 GPa) was observed using a microindenter. However, hardness of cementum and alveolar bone at any given age were significantly different (P<0.05). These observations should be taken into account as baseline parameters, during development (1.5 to 4 months), growth (4 to 10 months

  17. Proximity of AUG sequences to initiation codon in genomic 5' UTR regulates mammalian protein expression.

    PubMed

    Al-Ali, Ruslan; González-Sarmiento, Rogelio

    2016-12-15

    Protein expression can be controlled via AUG sequences located upstream to the initiation codon in the 5' end untranslated region (5' UTR). Our study was focused on the effect of distance between the initiation codon and the first upstream AUG. An inhibitory effect on protein expression was established when AUG exists in 5' UTR, and this effect is increased when multiple AUG sequences occur there. The study was performed with ATG16L2, a non-lethal gene with no introns or upstream AUG sequence to avoid any interference. New mutations were generated at different locations within the promoter region of ATG16L2 gene and added to a plasmid construct containing a luciferase gene reporter gene. The results show a clear relationship between the distance of the novel AUGs from initiation codon and protein expression. The inhibitory effect was even stronger when multiple AUG sequences were present in 5' UTR.

  18. Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins

    NASA Astrophysics Data System (ADS)

    Tang, Nicholas C.; Chilkoti, Ashutosh

    2016-04-01

    Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

  19. Translational selection frequently overcomes genetic drift in shaping synonymous codon usage patterns in vertebrates.

    PubMed

    Doherty, Aoife; McInerney, James O

    2013-10-01

    Synonymous codon usage patterns are shaped by a balance between mutation, drift, and natural selection. To date, detection of translational selection in vertebrates has proven to be a challenging task, obscured by small long-term effective population sizes in larger animals and the existence of isochores in some species. The consensus is that, in such species, natural selection is either completely ineffective at overcoming mutational pressures and genetic drift or perhaps is effective but so weak that it is not detectable. The aim of this research is to understand the interplay between mutation, selection, and genetic drift in vertebrates. We observe that although variation in mutational bias is undoubtedly the dominant force influencing codon usage, translational selection acts as a weak additional factor influencing synonymous codon usage. These observations indicate that translational selection is a widespread phenomenon in vertebrates and is not limited to a few species.

  20. Ribosome bypassing at serine codons as a test of the model of selective transfer RNA charging

    PubMed Central

    Lindsley, Dale; Bonthuis, Paul; Gallant, Jonathan; Tofoleanu, Teodora; Elf, Johan; Ehrenberg, Måns

    2005-01-01

    Recently, a model of the flux of amino acids through transfer RNAs (tRNAs) and into protein has been developed. The model predicts that the charging level of different isoacceptors carrying the same amino acid respond very differently to variation in supply of the amino acid or of the rate of charging. It has also been shown that ribosome bypassing is specifically stimulated at ‘hungry' codons calling for an aminoacyl-tRNA in short supply. We have constructed two reporters of bypassing, which differ only in the identity of the serine codon subjected to starvation. The stimulation of bypassing as a function of starvation differed greatly between the two serine codons, in good agreement with the quantitative predictions of the model. PMID:15678161

  1. Adaptive downregulation of pheomelanin-related Slc7a11 gene expression by environmentally induced oxidative stress.

    PubMed

    Galván, Ismael; Inácio, Ângela; Romero-Haro, Ana Angela; Alonso-Alvarez, Carlos

    2017-02-01

    Pheomelanin is a sulphur-containing yellow-to-reddish pigment whose synthesis consumes the main intracellular antioxidant (glutathione; GSH) and its precursor cysteine. Cysteine used for pheomelanogenesis cannot be used for antioxidant protection. We tested whether the expression of Slc7a11, the gene regulating the transport of cysteine to melanocytes for pheomelanogenesis, is environmentally influenced when cysteine/GSH are most required for antioxidant protection. We found that zebra finches Taeniopygia guttata developing pheomelanin-pigmented feathers during a 12-day exposure to the pro-oxidant diquat dibromide downregulated the expression of Slc7a11 in feather melanocytes, but not the expression of other genes that affect pheomelanogenesis by mechanisms different from cysteine transport such as MC1R and Slc45a2. Accordingly, diquat-treated birds did not suffer increased oxidative stress. This indicates that some animals have evolved an adaptive epigenetic lability that avoids damage derived from pheomelanogenesis. This mechanism should be explored in human Slc7a11 to help combat some cancer types related to cysteine consumption.

  2. Technology-delivered adaptations of motivational interviewing for health-related behaviors: A systematic review of the current research

    PubMed Central

    Shingleton, Rebecca M.; Palfai, Tibor P.

    2015-01-01

    Objectives The aims of this paper were to describe and evaluate the methods and efficacy of technology-delivered motivational interviewing interventions (TAMIs), discuss the challenges and opportunities of TAMIs, and provide a framework for future research. Methods We reviewed studies that reported using motivational interviewing (MI) based components delivered via technology and conducted ratings on technology description, comprehensiveness of MI, and study methods. Results The majority of studies were fully-automated and included at least one form of media rich technology to deliver the TAMI. Few studies provided complete descriptions of how MI components were delivered via technology. Of the studies that isolated the TAMI effects, positive changes were reported. Conclusion Researchers have used a range of technologies to deliver TAMIs suggesting feasibility of these methods. However, there are limited data regarding their efficacy, and strategies to deliver relational components remain a challenge. Future research should better characterize the components of TAMIs, empirically test the efficacy of TAMIs with randomized controlled trials, and incorporate fidelity measures. Practice Implications TAMIs are feasible to implement and well accepted. These approaches offer considerable potential to reduce costs, minimize therapist and training burden, and expand the range of clients that may benefit from adaptations of MI. PMID:26298219

  3. Improvement of adaptive GAs and back propagation ANNs performance in condition diagnosis of multiple bearing system using grey relational analysis.

    PubMed

    Wulandhari, Lili A; Wibowo, Antoni; Desa, Mohammad I

    2014-01-01

    Condition diagnosis of multiple bearings system is one of the requirements in industry field, because bearings are used in many equipment and their failure can result in total breakdown. Conditions of bearings commonly are reflected by vibration signals data. In multiple bearing condition diagnosis, it will involve many types of vibration signals data; thus, consequently, it will involve many features extraction to obtain precise condition diagnosis. However, large number of features extraction will increase the complexity of the diagnosis system. Therefore, in this paper, we presented a diagnosis method which is hybridization of adaptive genetic algorithms (AGAs), back propagation neural networks (BPNNs), and grey relational analysis (GRA) to diagnose the condition of multiple bearings system. AGAs are used in the diagnosis algorithm to determine the best initial weights of BPNNs in order to improve the diagnosis accuracy. In addition, GRA is applied to determine and select the dominant features from the vibration signal data which will provide good diagnosis of multiple bearings system in less features extraction. The experiments results show that AGAs-BPNNs with GRA approaches can increase the accuracy of diagnosis in shorter processing time, compared with the AGAs-BPNNs without the GRA.

  4. Improvement of Adaptive GAs and Back Propagation ANNs Performance in Condition Diagnosis of Multiple Bearing System Using Grey Relational Analysis

    PubMed Central

    Wulandhari, Lili A.; Wibowo, Antoni; Desa, Mohammad I.

    2014-01-01

    Condition diagnosis of multiple bearings system is one of the requirements in industry field, because bearings are used in many equipment and their failure can result in total breakdown. Conditions of bearings commonly are reflected by vibration signals data. In multiple bearing condition diagnosis, it will involve many types of vibration signals data; thus, consequently, it will involve many features extraction to obtain precise condition diagnosis. However, large number of features extraction will increase the complexity of the diagnosis system. Therefore, in this paper, we presented a diagnosis method which is hybridization of adaptive genetic algorithms (AGAs), back propagation neural networks (BPNNs), and grey relational analysis (GRA) to diagnose the condition of multiple bearings system. AGAs are used in the diagnosis algorithm to determine the best initial weights of BPNNs in order to improve the diagnosis accuracy. In addition, GRA is applied to determine and select the dominant features from the vibration signal data which will provide good diagnosis of multiple bearings system in less features extraction. The experiments results show that AGAs-BPNNs with GRA approaches can increase the accuracy of diagnosis in shorter processing time, compared with the AGAs-BPNNs without the GRA. PMID:25587265

  5. Adaptive spatio-temporal filtering for movement related potentials in EEG-based brain-computer interfaces.

    PubMed

    Lu, Jun; Xie, Kan; McFarland, Dennis J

    2014-07-01

    Movement related potentials (MRPs) are used as features in many brain-computer interfaces (BCIs) based on electroencephalogram (EEG). MRP feature extraction is challenging since EEG is noisy and varies between subjects. Previous studies used spatial and spatio-temporal filtering methods to deal with these problems. However, they did not optimize temporal information or may have been susceptible to overfitting when training data are limited and the feature space is of high dimension. Furthermore, most of these studies manually select data windows and low-pass frequencies. We propose an adaptive spatio-temporal (AST) filtering method to model MRPs more accurately in lower dimensional space. AST automatically optimizes all parameters by employing a Gaussian kernel to construct a low-pass time-frequency filter and a linear ridge regression (LRR) algorithm to compute a spatial filter. Optimal parameters are simultaneously sought by minimizing leave-one-out cross-validation error through gradient descent. Using four BCI datasets from 12 individuals, we compare the performances of AST filter to two popular methods: the discriminant spatial pattern filter and regularized spatio-temporal filter. The results demonstrate that our AST filter can make more accurate predictions and is computationally feasible.

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

    PubMed Central

    Grant, C M; Hinnebusch, A G

    1994-01-01

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

  7. Alpha-band phase synchrony is related to activity in the fronto-parietal adaptive control network

    PubMed Central

    Sadaghiani, Sepideh; Scheeringa, René; Lehongre, Katia; Morillon, Benjamin; Giraud, Anne-Lise; D’Esposito, Mark; Kleinschmidt, Andreas

    2014-01-01

    Neural oscillations in the α-band (8-12Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase-synchronization of α-oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the α-band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of α-band phase-synchrony. We adapted the phase-locking value (PLV) to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper α-band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well-known fronto-parietal (FP) network. Spectral correlations with this network’s activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale α phase-synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper α-band synchrony is well-suited to support these functions. Complementing our previous findings that related α-oscillation power to neural structures serving tonic control, the current findings link α phase-synchrony to neural structures underpinning phasic control of alertness and task requirements. PMID:23055501

  8. Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case-control study and meta-analysis.

    PubMed

    Sahu, S K; Chakrabarti, S; Roy, S D; Baishya, N; Reddy, R R; Suklabaidya, S; Kumar, A; Mohanty, S; Maji, S; Suryanwanshi, A; Rajasubramaniam, S; Asthana, M; Panda, A K; Singh, S P; Ganguly, S; Shaw, O P; Bichhwalia, A K; Sahoo, P K; Chattopadhyay, N R; Chatterjee, K; Kundu, C N; Das, A K; Kannan, R; Zorenpuii; Zomawia, E; Sema, S A; Singh, Y I; Ghosh, S K; Sharma, K; Das, B S; Choudhuri, T

    2016-05-09

    Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case-control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy-Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

  9. The TP53 codon 72 Pro/Pro genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis

    PubMed Central

    Wang, Xin; Hao, Li-Ran; Yue, Kai

    2015-01-01

    Background: The polymorphism of TP53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Chinese have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of TP53 codon 72 Arg/Pro polymorphism on the development of lung cancer in the Chinese population. Material/Methods: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 10 October 2014. Pooled ORs and 95% CIs were used to assess the strength of the associations. Results: A total of 12 case-control studies including 3681 lung cancer cases and 4358 controls were involved in this meta-analysis. Overall, no significant association was found between TP53 codon 72 variation and lung cancer risk when all studies in the Chinese population pooled into this meta-analysis. However, in the subgroup analysis by geographical locations, significantly increased risk was found in the population from North China under all genetic models (Allele model, OR=1.22, 95% CI: 1.04-1.43; Dominant model, OR=1.13, 95% CI: 1.01-1.25; Recessive model, OR=1.41, 95% CI: 1.07-1.87; Homozygous model, OR=1.47, 95% CI: 1.09-1.99; Heterozygous model, OR=1.40, 95% CI: 1.04-1.89). Conclusions: This meta-analysis provides the evidence that TP53 codon 72 polymorphism may contribute to the lung cancer development in North China and studies with large sample size and gene-gene (gene-environment) interactions are warranted to verify this finding. PMID:26064201

  10. Group-specific identification of polioviruses by PCR using primers containing mixed-base or deoxyinosine residue at positions of codon degeneracy.

    PubMed Central

    Kilpatrick, D R; Nottay, B; Yang, C F; Yang, S J; Mulders, M N; Holloway, B P; Pallansch, M A; Kew, O M

    1996-01-01

    We have developed a method for differentiating polioviruses from nonpolio enteroviruses using PCR. A pair of panpoliovirus PCR primers were designed to match intervals encoding amino acid sequences within VP1 that are strongly conserved among polioviruses. The initiating primer hybridizes with codons of a 7-amino-acid sequence that has been found only in polioviruses; the second primer matches codons of a domain thought to interact with the cell receptor. The panpoliovirus PCR primers contain mixed-base and deoxyinosine residues to compensate for the high degeneracy of the targeted codons. All RNAs from 48 vaccine-related and 110 wild poliovirus isolates of all three serotypes served as efficient templates for amplification of 79-bp product. None of the genomic sequences of 49 nonpolio enterovirus reference strains were amplified under equivalent reaction conditions. Sensitivities of poliovirus detection were as low as 100 fg (equivalent to approximately 25,000 genomic copies or 25 to 250 PFU) when the amplified products were visualized by ethidium bromide fluorescence. These degenerate PCR primers should aid in the detection of all polioviruses, including those wild poliovirus isolates for which genotype-specific reagents are unavailable. PMID:8940436

  11. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy).

    PubMed Central

    Ahmad, N N; Ala-Kokko, L; Knowlton, R G; Jimenez, S A; Weaver, E J; Maguire, J I; Tasman, W; Prockop, D J

    1991-01-01

    Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein. Images PMID:1677770

  12. Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)

    SciTech Connect

    Ahmad, N.N.; Ala-Kokko, L.; Knowlton, R.G.; Jimenez, S.A.; Weaver, E.J.; Prockop, D.J. ); Maguire, J.I.; Tasman, W. )

    1991-08-01

    Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position {alpha}1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at {alpha}1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.

  13. Short repeats in the spa gene of Staphylococcus aureus are prone to nonsense mutations: stop codons can be found in strains isolated from patients with generalized infection.

    PubMed

    Khrustalev, Vladislav Victorovich; Ghaznavi-Rad, Ehsanollah; Neela, Vasanthakumari; Shamsudin, Mariana-Nor; Amouzandeh-Nobaveh, Alireza; Barkovsky, Eugene Victorovich

    2013-11-01

    Fifteen sequences with stop codons have been obtained in the course of standard methicillin-resistant Staphylococcus aureus (MRSA) spa typing. In nine of those sequences, stop codons occurred due to nonsense G-T and A-T transversions. G-T transversions would appear to be frequent in the spa gene, mostly due to symmetric mutational AT-pressure in the whole S. aureus genome and due to replication-associated mutational pressure characteristic of lagging strands of the "chromosome". A-T transversions would appear to be frequent in the spa gene mostly due to transcription-associated mutational pressure. Relative to other S. aureus genes, short repeats in spa are enriched by nonsense sites for G-T and A-T transversions; the probability of being nonsense for A-T transversion is high in that part of spa coding region. 13 out of 15 (87%) of the sequences with stop codons were obtained from strains isolated from patients with generalized S. aureus infection. Truncation of spa at its C-terminus is predicted to result in a protein that possesses functional IgG binding domains unable to be linked to the cell wall. This is discussed in light of the known fact that extracellular spa is a strong virulence factor involved in immune evasion.

  14. Modeling late-life adaptation in affective well-being under a severe chronic health condition: the case of age-related macular degeneration.

    PubMed

    Schilling, Oliver K; Wahl, Hans-Werner

    2006-12-01

    Age-related macular degeneration (AMD) was used as a case model to longitudinally study adaptation in affective well-being under a prevalent chronic health condition. Measures of positive and negative affect, obtained at 5 subsequent measurement occasions with 3-month intervals in between, were analyzed in 90 older adults diagnosed with AMD. The authors proposed a pattern of adaptation that shows initial decline in affective well-being after disease outbreak, followed by a turnaround into a restorative phase of increase, implying nonlinear intraindividual trajectories, with changes substantially related to disease duration. Analysis was conducted by means of a nonlinear mixed models approach. Results confirmed the hypothesized adaptation pattern for positive affect but not for negative affect, which was found more stable across measurement occasions.

  15. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

    NASA Technical Reports Server (NTRS)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  16. A Hypothetical Perspective on the Relative Contributions of Strategic and Adaptive Control Mechanisms in Plastic Recalibration of Locomotor Heading Direction

    NASA Technical Reports Server (NTRS)

    Richards, J. T.; Mulavara, A. P.; Ruttley, T.; Peters, B. T.; Warren, L. E.; Bloomberg, J. J.

    2006-01-01

    We have previously shown that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of the control of position and trajectory during over-ground locomotion, which functionally reflects adaptive changes in the sensorimotor integration of visual, vestibular, and proprioceptive cues (Mulavara et al., 2005). The objective of this study was to investigate how strategic changes in torso control during exposure to simulated rotary self-motion during treadmill walking influences adaptive modification of locomotor heading direction during over-ground stepping.

  17. Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol.

    PubMed

    Wang, Xin; Li, Bing-Zhi; Ding, Ming-Zhu; Zhang, Wei-Wen; Yuan, Ying-Jin

    2013-03-01

    During hydrolysis of lignocellulosic biomass, a broad range of inhibitors are generated, which interfere with yeast growth and bioethanol production. In order to improve the strain tolerance to multiple inhibitors--acetic acid, furfural, and phenol (three representative lignocellulose-derived inhibitors) and uncover the underlying tolerant mechanism, an adaptation experiment was performed in which the industrial Saccharomyces cerevisiae was cultivated repeatedly in a medium containing multiple inhibitors. The adaptation occurred quickly, accompanied with distinct increase in growth rate, glucose utilization rate, furfural metabolism rate, and ethanol yield, only after the first transfer. A similar rapid adaptation was also observed for the lab strains of BY4742 and BY4743. The metabolomic analysis was employed to investigate the responses of the industrial S. cereviaise to three inhibitors during the adaptation. The results showed that higher levels of 2-furoic acid, 2, 3-butanediol, intermediates in glycolytic pathway, and amino acids derived from glycolysis, were discovered in the adapted strains, suggesting that enhanced metabolic activity in these pathways may relate to resistance against inhibitors. Additionally, through single-gene knockouts, several genes related to alanine metabolism, GABA shunt, and glycerol metabolism were verified to be crucial for the resistance to multiple inhibitors. This study provides new insights into the tolerance mechanism against multiple inhibitors, and guides for the improvement of tolerant ethanologenic yeast strains for lignocellulose-bioethanol fermentation.

  18. Local adaptation (mostly) remains local: reassessing environmental associations of climate-related candidate SNPs in Arabidopsis halleri.

    PubMed

    Rellstab, C; Fischer, M C; Zoller, S; Graf, R; Tedder, A; Shimizu, K K; Widmer, A; Holderegger, R; Gugerli, F

    2017-02-01

    Numerous landscape genomic studies have identified single-nucleotide polymorphisms (SNPs) and genes potentially involved in local adaptation. Rarely, it has been explicitly evaluated whether these environmental associations also hold true beyond the populations studied. We tested whether putatively adaptive SNPs in Arabidopsis halleri (Brassicaceae), characterized in a previous study investigating local adaptation to a highly heterogeneous environment, show the same environmental associations in an independent, geographically enlarged set of 18 populations. We analysed new SNP data of 444 plants with the same methodology (partial Mantel tests, PMTs) as in the original study and additionally with a latent factor mixed model (LFMM) approach. Of the 74 candidate SNPs, 41% (PMTs) and 51% (LFMM) were associated with environmental factors in the independent data set. However, only 5% (PMTs) and 15% (LFMM) of the associations showed the same environment-allele relationships as in the original study. In total, we found 11 genes (31%) containing the same association in the original and independent data set. These can be considered prime candidate genes for environmental adaptation at a broader geographical scale. Our results suggest that selection pressures in highly heterogeneous alpine environments vary locally and signatures of selection are likely to be population-specific. Thus, genotype-by-environment interactions underlying adaptation are more heterogeneous and complex than is often assumed, which might represent a problem when testing for adaptation at specific loci.

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

    PubMed Central

    Frenkel-Morgenstern, Milana; Danon, Tamar; Christian, Thomas; Igarashi, Takao; Cohen, Lydia; Hou, Ya-Ming; Jensen, Lars Juhl

    2012-01-01

    The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle-regulated genes with that of other genes, we discovered that there is a significant preference for non-optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non-optimal codon preferences. Remarkably, cell cycle-regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non-optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl-, threonyl-, and glutamyl-prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non-optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell-cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle-dependent dynamics of proteins. PMID:22373820

  20. Characterization of the stop codon readthrough signal of Colorado tick fever virus segment 9 RNA.

    PubMed

    Napthine, Sawsan; Yek, Christina; Powell, Michael L; Brown, T David K; Brierley, Ian

    2012-02-01

    Termination codon readthrough is utilized as a mechanism of expression of a growing number of viral and cellular proteins, but in many cases the mRNA signals that promote readthrough are poorly characterized. Here, we investigated the readthrough signal of Colorado tick fever virus (CTFV) segment 9 RNA (Seg-9). CTFV is the type-species of the genus Coltivirus within the family Reoviridae and is a tick-borne, double-stranded, segmented RNA virus. Seg-9 encodes a 36-kDa protein VP9, and by readthrough of a UGA stop codon, a 65-kDa product, VP9'. Using a reporter system, we defined the minimal sequence requirements for readthrough and confirmed activity in both mammalian and insect cell-free translation systems, and in transfected mammalian cells. Mutational analysis revealed that readthrough was UGA specific, and that the local sequence context around the UGA influenced readthrough efficiency. Readthrough was also dependent upon a stable RNA stem-loop structure beginning eight bases downstream from the UGA codon. Mutational analysis of this stem-loop revealed a requirement for the stem region but not for substructures identified within the loop. Unexpectedly, we were unable to detect a ribosomal pause during translation of the CTFV signal, suggesting that the mechanism of readthrough, at least at this site, is unlikely to be dependent upon RNA secondary-structure induced ribosomal pausing at the recoded stop codon.

  1. p53 codon 72 polymorphism in vulval cancer and vulval intraepithelial neoplasia

    PubMed Central

    Rosenthal, A N; Ryan, A; Hopster, D; Jacobs, I J

    2000-01-01

    p53 codon 72 polymorphism was analysed in UK women with human papillomavirus (HPV)-associated vulval intraepithelial neoplasia and vulval squamous cell carcinoma. Arginine homozygotes were significantly less common in either group compared with controls. We conclude that the arginine polymorphism may confer protection against the development of HPV-associated vulval neoplasia. © 2000 Cancer Research Campaign PMID:11044351

  2. System analysis of synonymous codon usage biases in archaeal virus genomes.

    PubMed

    Li, Sen; Yang, Jie

    2014-08-21

    Recent studies of geothermally heated aquatic ecosystems have found widely divergent viruses with unusual morphotypes. Archaeal viruses isolated from these hot habitats usually have double-stranded DNA genomes, linear or circular, and can infect members of the Archaea domain. In this study, the synonymous codon usage bias (SCUB) and dinucleotide composition in the available complete archaeal virus genome sequences have been investigated. It was found that there is a significant variation in SCUB among different Archaeal virus species, which is mainly determined by the base composition. The outcome of correspondence analysis (COA) and Spearman׳s rank correlation analysis shows that codon usage of selected archaeal virus genes depends mainly on GC richness of genome, and the gene׳s function, albeit with smaller effects, also contributes to codon usage in this virus. Furthermore, this investigation reveals that aromaticity of each protein is also critical in affecting SCUB of these viral genes although it was less important than that of the mutational bias. Especially, mutational pressure may influence SCUB in SIRV1, SIRV2, ARV1, AFV1, and PhiCh1 viruses, whereas translational selection could play a leading role in HRPV1׳s SCUB. These conclusions not only can offer an insight into the codon usage biases of archaeal virus and subsequently the possible relationship between archaeal viruses and their host, but also may help in understanding the evolution of archaeal viruses and their gene classification, and more helpful to explore the origin of life and the evolution of biology.

  3. Genetic analysis of diversity within a Chinese local sugarcane germplasm based on start codon targeted polymorphism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In-depth information on sugarcane germplasm is the basis for its conservation and utilization. Data on sugarcane molecular markers are limited for the Chinese sugarcane germplasm collections. In the present study, 20 start codon targeted (SCoT) marker primers were designed to assess the genetic dive...

  4. Four-base codons ACCA, ACCU and ACCC are recognized by frameshift suppressor sufJ.

    PubMed

    Bossi, L; Roth, J R

    1981-08-01

    The frameshift suppressor sufJ acts to correct a set of +1 frameshift mutations having very different sequences at their mutant sites. This suppressor acts by reading a 4 base codon located near, but not at, the site of each suppressible mutation. Suppression thus necessitates out-of-phase translation of the short stretch of mRNA between the site of action of the suppressor tRNA and the site of the frameshift mutation. We have identified the site read by sufJ by mutationally creating a series of such sites in the neighborhood of a previously nonsuppressible frameshift mutation. Each of the newly generated sites was formed by base substitution. Four independently generated sites were analyzed by DNA sequencing. At each site the quadruplet codon ACCX was generated (where X is A, U or C). Thus sufJ is able to read a 4 base codon in which any of three bases is acceptable in the fourth position. This is the first frameshift suppressor that does not read a run of three repeated bases in the first three positions of its codon.

  5. Cryo-EM study of start codon selection during archaeal translation initiation

    PubMed Central

    Coureux, Pierre-Damien; Lazennec-Schurdevin, Christine; Monestier, Auriane; Larquet, Eric; Cladière, Lionel; Klaholz, Bruno P.; Schmitt, Emmanuelle; Mechulam, Yves

    2016-01-01

    Eukaryotic and archaeal translation initiation complexes have a common structural core comprising e/aIF1, e/aIF1A, the ternary complex (TC, e/aIF2-GTP-Met-tRNAiMet) and mRNA bound to the small ribosomal subunit. e/aIF2 plays a crucial role in this process but how this factor controls start codon selection remains unclear. Here, we present cryo-EM structures of the full archaeal 30S initiation complex showing two conformational states of the TC. In the first state, the TC is bound to the ribosome in a relaxed conformation with the tRNA oriented out of the P site. In the second state, the tRNA is accommodated within the peptidyl (P) site and the TC becomes constrained. This constraint is compensated by codon/anticodon base pairing, whereas in the absence of a start codon, aIF2 contributes to swing out the tRNA. This spring force concept highlights a mechanism of codon/anticodon probing by the initiator tRNA directly assisted by aIF2. PMID:27819266

  6. Transfer RNA gene arrangement and codon usage in vertebrate mitochondrial genomes: a new insight into gene order conservation

    PubMed Central

    2010-01-01

    Background Mitochondrial (mt) gene arrangement has been highly conserved among vertebrates from jawless fishes to mammals for more than 500 million years. It remains unclear, however, whether such long-term persistence is a consequence of some constraints on the gene order. Results Based on the analysis of codon usage and tRNA gene positions, we suggest that tRNA gene order of the typical vertebrate mt-genomes may be important for their translational efficiency. The vertebrate mt-genome encodes 2 rRNA, 22 tRNA, and 13 transmembrane proteins consisting mainly of hydrophobic domains. We found that the tRNA genes specifying the hydrophobic residues were positioned close to the control region (CR), where the transcription efficiency is estimated to be relatively high. Using 47 vertebrate mt-genome sequences representing jawless fishes to mammals, we further found a correlation between codon usage and tRNA gene positions, implying that highly-used tRNA genes are located close to the CR. In addition, an analysis considering the asymmetric nature of mtDNA replication suggested that the tRNA loci that remain in single-strand for a longer time tend to have more guanine and thymine not suffering deamination mutations in their anticodon sites. Conclusions Our analyses imply the existence of translational constraint acting on the vertebrate mt-gene arrangement. Such translational constraint, together with the deamination-related constraint, may have contributed to long-term maintenance of gene order. PMID:20723209

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

    PubMed

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

    2013-12-01

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

  8. Towards More Comprehensive Projections of Urban Heat-Related Mortality: Estimates for New York City under Multiple Population, Adaptation, and Climate Scenarios

    PubMed Central

    Petkova, Elisaveta P.; Vink, Jan K.; Horton, Radley M.; Gasparrini, Antonio; Bader, Daniel A.; Francis, Joe D.; Kinney, Patrick L.

    2016-01-01

    Background: High temperatures have substantial impacts on mortality and, with growing concerns about climate change, numerous studies have developed projections of future heat-related deaths around the world. Projections of temperature-related mortality are often limited by insufficient information to formulate hypotheses about population sensitivity to high temperatures and future demographics. Objectives: The present study derived projections of temperature-related mortality in New York City by taking into account future patterns of adaptation or demographic change, both of which can have profound influences on future health burdens. Methods: We adopted a novel approach to modeling heat adaptation by incorporating an analysis of the observed population response to heat in New York City over the course of eight decades. This approach projected heat-related mortality until the end of the 21st century based on observed trends in adaptation over a substantial portion of the 20th century. In addition, we incorporated a range of new scenarios for population change until the end of the 21st century. We then estimated future heat-related deaths in New York City by combining the changing temperature–mortality relationship and population scenarios with downscaled temperature projections from the 33 global climate models (GCMs) and two Representative Concentration Pathways (RCPs). Results: The median number of projected annual heat-related deaths across the 33 GCMs varied greatly by RCP and adaptation and population change scenario, ranging from 167 to 3,331 in the 2080s compared with 638 heat-related deaths annually between 2000 and 2006. Conclusions: These findings provide a more complete picture of the range of potential future heat-related mortality risks across the 21st century in New York City, and they highlight the importance of both demographic change and adaptation responses in modifying future risks. Citation: Petkova EP, Vink JK, Horton RM, Gasparrini A, Bader

  9. Structural characterization of eRF1 mutants indicate a complex mechanism of stop codon recognition

    PubMed Central

    Pillay, Shubhadra; Li, Yan; Wong, Leo E; Pervushin, Konstantin

    2016-01-01

    Eukarya translation termination requires the stop codon recognizing protein eRF1. In contrast to the multiple proteins required for translation termination in Bacteria, eRF1 retains the ability to recognize all three of the stop codons. The details of the mechanism that eRF1 uses to recognize stop codons has remained elusive. This study describes the structural effects of mutations in the eRF1 N-domain that have previously been shown to alter stop codon recognition specificity. Here, we propose a model of eRF1 binding to the pre-translation termination ribosomal complex that is based in part on our solution NMR structures of the wild-type and mutant eRF1 N-domains. Since structural perturbations induced by these mutations were spread throughout the protein structure, residual dipolar coupling (RDC) data were recorded to establish the long-range effects of the specific mutations, E55Q, Y125F, Q122FM(Y)F126. RDCs were recorded on 15N-labeled eRF1 N-domain weakly aligned in either 5% w/v n-octyl-penta (ethylene glycol)/octanol (C8E5) or the filamentous phage Pf1. These data indicate that the mutations alter the conformation and dynamics of the GTS loop that is distant from the mutation sites. We propose that the GTS loop forms a switch that is key for the multiple codon recognition capability of eRF1. PMID:26725946

  10. Codon reassignment to facilitate genetic engineering and biocontainment in the chloroplast of Chlamydomonas reinhardtii.

    PubMed

    Young, Rosanna E B; Purton, Saul

    2016-05-01

    There is a growing interest in the use of microalgae as low-cost hosts for the synthesis of recombinant products such as therapeutic proteins and bioactive metabolites. In particular, the chloroplast, with its small, genetically tractable genome (plastome) and elaborate metabolism, represents an attractive platform for genetic engineering. In Chlamydomonas reinhardtii, none of the 69 protein-coding genes in the plastome uses the stop codon UGA, therefore this spare codon can be exploited as a useful synthetic biology tool. Here, we report the assignment of the codon to one for tryptophan and show that this can be used as an effective strategy for addressing a key problem in chloroplast engineering: namely, the assembly of expression cassettes in Escherichia coli when the gene product is toxic to the bacterium. This problem arises because the prokaryotic nature of chloroplast promoters and ribosome-binding sites used in such cassettes often results in transgene expression in E. coli, and is a potential issue when cloning genes for metabolic enzymes, antibacterial proteins and integral membrane proteins. We show that replacement of tryptophan codons with the spare codon (UGG→UGA) within a transgene prevents functional expression in E. coli and in the chloroplast, and that co-introduction of a plastidial trnW gene carrying a modified anticodon restores function only in the latter by allowing UGA readthrough. We demonstrate the utility of this system by expressing two genes known to be highly toxic to E. coli and discuss its value in providing an enhanced level of biocontainment for transplastomic microalgae.

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

    PubMed Central

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

    2009-01-01

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

  12. Terminating eukaryote translation: domain 1 of release factor eRF1 functions in stop codon recognition.

    PubMed Central

    Bertram, G; Bell, H A; Ritchie, D W; Fullerton, G; Stansfield, I

    2000-01-01

    Eukaryote ribosomal translation is terminated when release factor eRF1, in a complex with eRF3, binds to one of the three stop codons. The tertiary structure and dimensions of eRF1 are similar to that of a tRNA, supporting the hypothesis that release factors may act as molecular mimics of tRNAs. To identify the yeast eRF1 stop codon recognition domain (analogous to a tRNA anticodon), a genetic screen was performed to select for mutants with disabled recognition of only one of the three stop codons. Nine out of ten mutations isolated map to conserved residues within the eRF1 N-terminal domain 1. A subset of these mutants, although wild-type for ribosome and eRF3 interaction, differ in their respective abilities to recognize each of the three stop codons, indicating codon-specific discrimination defects. Five of six of these stop codon-specific mutants define yeast domain 1 residues (I32, M48, V68, L123, and H129) that locate at three pockets on the eRF1 domain 1 molecular surface into which a stop codon can be modeled. The genetic screen results and the mutant phenotypes are therefore consistent with a role for domain 1 in stop codon recognition; the topology of this eRF1 domain, together with eRF1-stop codon complex modeling further supports the proposal that this domain may represent the site of stop codon binding itself. PMID:10999601

  13. Adapting coastal structures to a moving relative sea level: Roman Time geoarchaeological evidence from Posillipo promontory (Naples, Italy).

    NASA Astrophysics Data System (ADS)

    Aucelli, Pietro; Cinque, Aldo; Giordano, Francesco; Mattei, Gaia; Pappone, Gerardo; Rizzo, Angela

    2016-04-01

    precisely measuring the present submersion of all remains, two paleo-sea levels has been detected: one for the 1st century BC at -4 / -5 m and another for the 1st century AD at -3 + -0.50 m. In conclusion, by comparing the relative palaeo-sea level we have found with the eustatic curve (Lambeck et al 2011), it appears that Posillipo area suffered 2 +/- 0.3m of subsidence after the 1st century AD. Moreover, the new interpretations we present here, strongly suggest that Posillipo area was also affected by subsidence between the 1st century BC and the 1st century AD, when the landmass sank about 1.5/2.5 m. Eventhough these movements appear less strong than those recognized in the Campi Flegrei central caldera, our results prove that volcano-tectonic movements of at least metrical magnitude have occurred also outside the caldera. In terms of human adaptation to the subsidence-induced rise of sea level during Roman times, the archaeological remains of Marechiaro e Rosbery indicate that the villas were restructured closing the rooms submerged by the sea.

  14. Establishment of joint attention in dyads involving hearing mothers of deaf and hearing children, and its relation to adaptive social behavior.

    PubMed

    Nowakowski, Matilda E; Tasker, Susan L; Schmidt, Louis A

    2009-01-01

    Mounting evidence points to joint attention as a mediating variable in children's adaptive behavior development. Joint attention in interactions between hearing mothers and congenitally deaf (n = 27) and hearing (n = 29) children, ages 18-36 months, was examined. All deaf children had severe to profound hearing loss. Mother-child interactions were coded for maternally initiated and child-initiated success rates in establishing joint attention; mothers completed ratings of their children's adaptive behavior. Hearing mother-deaf child dyads had significantly lower maternally initiated success rates. No significant between-group differences on child-initiated success rates were shown. Maternal ratings of adaptive behavior were significantly lower for deaf children, and related positively and significantly to both child-initiated and maternally initiated success rates. The findings suggest that mother-child interactions that are low in successful establishment of joint attention might mediate the development of socioemotional problems evident in deaf children with hearing families.

  15. A general risk-based adaptive management scheme incorporating the Bayesian Network Relative Risk Model with the South River, Virginia, as case study.

    PubMed

    Landis, Wayne G; Markiewicz, April J; Ayre, Kim K; Johns, Annie F; Harris, Meagan J; Stinson, Jonah M; Summers, Heather M

    2017-01-01

    Adaptive management has been presented as a method for the remediation, restoration, and protection of ecological systems. Recent reviews have found that the implementation of adaptive management has been unsuccessful in many instances. We present a modification of the model first formulated by Wyant and colleagues that puts ecological risk assessment into a central role in the adaptive management process. This construction has 3 overarching segments. Public engagement and governance determine the goals of society by identifying endpoints and specifying constraints such as costs. The research, engineering, risk assessment, and management section contains the decision loop estimating risk, evaluating options, specifying the monitoring program, and incorporating the data to re-evaluate risk. The 3rd component is the recognition that risk and public engagement can be altered by various externalities such as climate change, economics, technological developments, and population growth. We use the South River, Virginia, USA, study area and our previous research to illustrate each of these components. In our example, we use the Bayesian Network Relative Risk Model to estimate risks, evaluate remediation options, and provide lists of monitoring priorities. The research, engineering, risk assessment, and management loop also provides a structure in which data and the records of what worked and what did not, the learning process, can be stored. The learning process is a central part of adaptive management. We conclude that risk assessment can and should become an integral part of the adaptive management process. Integr Environ Assess Manag 2017;13:115-126. © 2016 SETAC.

  16. Measures of resilience and adaptation of adolescents in single parent families in Taiwan: psychometric properties and related profiles.

    PubMed

    Hsieh, Mei O; Shek, Daniel T L

    2007-01-01

    The dimensionality of measures of resilience (74 items) and adaptation (35 items) were examined in 291 adolescents living in single parent families in Taiwan. Factor analyses showed that internally consistent factors with high loadings could be derived from: (a) resilience items with reference to different ecological systems, including personal domain (six factors), family domain (eight domains), school domain (three domains), and community domain (three domains); and (b) adaptation problem items (eight factors). An examination of the profile of responses of the respondents showed that several concerns in the areas of resilience (effective coping, parental protection from being hurt by parental divorce, home-school cooperation, and connection with outside resources) and adaptation (problems in academic aspirations, low self-regard, and low self-control) were identified.

  17. Genomic, Transcriptomic, and Proteomic Analysis Provide Insights Into the Cold Adaptation Mechanism of the Obligate Psychrophilic Fungus Mrakia psychrophila

    PubMed Central

    Su, Yao; Jiang, Xianzhi; Wu, Wenping; Wang, Manman; Hamid, M. Imran; Xiang, Meichun; Liu, Xingzhong

    2016-01-01

    Mrakia psychrophila is an obligate psychrophilic fungus. The cold adaptation mechanism of psychrophilic fungi remains unknown. Comparative genomics analysis indicated that M. psychrophila had a specific codon usage preference, especially for codons of Gly and Arg and its major facilitator superfamily (MFS) transporter gene family was expanded. Transcriptomic analysis revealed that genes involved in ribosome and energy metabolism were upregulated at 4°, while genes involved in unfolded protein binding, protein processing in the endoplasmic reticulum, proteasome, spliceosome, and mRNA surveillance were upregulated at 20°. In addition, genes related to unfolded protein binding were alternatively spliced. Consistent with other psychrophiles, desaturase and glycerol 3-phosphate dehydrogenase, which are involved in biosynthesis of unsaturated fatty acid and glycerol respectively, were upregulated at 4°. Cold adaptation of M. psychrophila is mediated by synthesizing unsaturated fatty acids to maintain membrane fluidity and accumulating glycerol as a cryoprotectant. The proteomic analysis indicated that the correlations between the dynamic patterns between transcript level changes and protein level changes for some pathways were positive at 4°, but negative at 20°. The death of M. psychrophila above 20° might be caused by an unfolded protein response. PMID:27633791

  18. Adapting to the Changing Climate: An Assessment of Local Health Department Preparations for Climate Change-Related Health Threats, 2008-2012

    PubMed Central

    Roser-Renouf, Connie; Maibach, Edward W.; Li, Jennifer

    2016-01-01

    Background Climate change poses a major public health threat. A survey of U.S. local health department directors in 2008 found widespread recognition of the threat, but limited adaptive capacity, due to perceived lack of expertise and other resources. Methods We assessed changes between 2008 and 2012 in local public health departments' preparedness for the public health threats of climate change, in light of increasing national polarization on the issue, and widespread funding cutbacks for public health. A geographically representative online survey of directors of local public health departments was conducted in 2011–2012 (N = 174; response rate = 50%), and compared to the 2008 telephone survey results (N = 133; response rate = 61%). Results Significant polarization had occurred: more respondents in 2012 were certain that the threat of local climate change impacts does/does not exist, and fewer were unsure. Roughly 10% said it is not a threat, compared to 1% in 2008. Adaptation capacity decreased in several areas: perceived departmental expertise in climate change risk assessment; departmental prioritization of adaptation; and the number of adaptation-related programs and services departments provided. In 2008, directors' perceptions of local impacts predicted the number of adaptation-related programs and services their departments offered, but in 2012, funding predicted programming and directors' impact perceptions did not. This suggests that budgets were constraining directors' ability to respond to local climate change-related health threats. Results also suggest that departmental expertise may mitigate funding constraints. Strategies for overcoming these obstacles to local public health departments' preparations for climate change are discussed. PMID:26991658

  19. When History Repeats Itself: Exploring the Genetic Architecture of Host-Plant Adaptation in Two Closely Related Lepidopteran Species

    PubMed Central

    Alexandre, Hermine; Ponsard, Sergine; Bourguet, Denis; Vitalis, Renaud; Audiot, Philippe; Cros-Arteil, Sandrine; Streiff, Réjane

    2013-01-01

    The genus Ostrinia includes two allopatric maize pests across Eurasia, namely the European corn borer (ECB, O. nubilalis) and the Asian corn borer (ACB, O. furnacalis). A third species, the Adzuki bean borer (ABB, O. scapulalis), occurs in sympatry with both the ECB and the ACB. The ABB mostly feeds on native dicots, which probably correspond to the ancestral host plant type for the genus Ostrinia. This situation offers the opportunity to characterize the two presumably independent adaptations or preadaptations to maize that occurred in the ECB and ACB. In the present study, we aimed at deciphering the genetic architecture of these two adaptations to maize, a monocot host plant recently introduced into Eurasia. To this end, we performed a genome scan analysis based on 684 AFLP markers in 12 populations of ECB, ACB and ABB. We detected 2 outlier AFLP loci when comparing French populations of the ECB and ABB, and 9 outliers when comparing Chinese populations of the ACB and ABB. These outliers were different in both countries, and we found no evidence of linkage disequilibrium between any two of them. These results suggest that adaptation or preadaptation to maize relies on a different genetic architecture in the ECB and ACB. However, this conclusion must be considered in light of the constraints inherent to genome scan approaches and of the intricate evolution of adaptation and reproductive isolation in the Ostrinia spp. complex. PMID:23874914

  20. VEGF189 expression is highly related to adaptation of the plateau pika (Ochotona curzoniae) inhabiting high altitudes.

    PubMed

    Li, Hongge; Guo, Songchang; Ren, Yongming; Wang, Depeng; Yu, Honghao; Li, Wenjing; Zhao, Xinquan; Chang, Zhijie

    2013-12-01

    The plateau pika (Ochotona curzonia) has adapted to high-altitude hypoxia during evolution. Higher microvessel density in specific tissues and a blunted hypoxic pulmonary vasoconstriction response are the critical components of this adaptation. VEGF, vascular endothelial growth factor, has proved to be a key regulator of angiogenesis in response to tissue hypoxia and to play an important role in vascular vasodilation. However, the role of VEGF in adaptation to high-altitude hypoxia in the plateau pika remains unknown. In this study, we cloned cDNAs for VEGF165 and VEGF189 and examined their expression in pikas inhabiting altitudes of 3200 and 4750 m. Phylogenetic analysis reveals that pika VEGF165 and VEGF189 are evolutionarily conserved. Real-time PCR analysis demonstrates that VEGF165 and VEGF189 display tissue and altitude-specific expression patterns. Interestingly, we found that the levels of VEGF189 mRNA are significantly higher than those of VEGF165 in the brain and muscle tissues of the pika, which is different from what was previously observed in sea-level mammals. VEGF189 mRNA levels in brain, muscle, and lung of the pika increased with increased habitat altitude, whereas VEGF165 shows less change. Our study suggests an important role for VEGF189 in adaptation to hypoxia by the plateau pika in the high-altitude environment.

  1. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2015-12-01

    mice, despite a considerable and sustained decrease in sensory nerve activity. Physiological adaptations during development may allow mice to...Department of Anatomy, Physiology , & Cell Biology, USA Abstract Objectives: The present study sought to determine the effects of decreased peripheral...differences in bone parameters in capsaicin-treated mice, despite a considerable and sustained decrease in sensory nerve activity. Physiological

  2. Using Structural Equation Modeling to Validate Online Game Players' Motivations Relative to Self-Concept and Life Adaptation

    ERIC Educational Resources Information Center

    Yang, Shu Ching; Huang, Chiao Ling

    2013-01-01

    This study aimed to validate a systematic instrument to measure online players' motivations for playing online games (MPOG) and examine how the interplay of differential motivations impacts young gamers' self-concept and life adaptation. Confirmatory factor analysis determined that a hierarchical model with a two-factor structure of…

  3. The Link between Age, Career Goals, and Adaptive Development for Work-Related Learning among Local Government Employees

    ERIC Educational Resources Information Center

    Tones, Megan; Pillay, Hitendra; Kelly, Kathy

    2011-01-01

    More recently, lifespan development psychology models of adaptive development have been applied to the workforce to investigate ageing worker and lifespan issues. The current study uses the Learning and Development Survey (LDS) to investigate employee selection and engagement of learning and development goals and opportunities and constraints for…

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

    PubMed Central

    2010-01-01

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

  5. Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk.

    PubMed

    Lv, Long; Wang, Ping; Zhou, Xiaoqing; Sun, Beicheng

    2013-06-01

    Previous studies regarding the association of p53 codon 72 Arg/Pro polymorphism with hepatocellular carcinoma (HCC) risk have provided conflicting and inconclusive findings. Thus, a meta-analysis of all currently available publications was performed to address this issue. Eleven individual case-control studies involving a total of 2,718 cases and 3,752 controls were identified after a systematic search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association of p53 codon 72 Arg/Pro polymorphism with HCC risk was estimated by the pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI). Subgroup analyses stratified by ethnicity, source of controls, gender, hepatitis virus infection status, and family history of HCC were also conducted to assess the association. Overall, significantly increased risk of HCC was identified among carriers of the homozygous genotype ProPro (ORProPro vs. ArgArg=1.38 (95 % CI, 1.03-1.85), P OR=0.033; ORProPro vs. ArgArg + ArgPro =1.28 (95 % CI, 1.03-1.59), P OR=0.026). In subgroup analysis by ethnicity, the pooled results suggested that the p53 codon 72 Arg/Pro polymorphism was associated with an increased risk of HCC in Asians and Caucasians (for Asians, ORProPro vs. ArgArg + ArgPro=1.17 (95 % CI, 1.02-1.34), P OR=0.025; for Caucasians, ORProPro vs. ArgArg = 1.65 (95 % CI, 1.07-2.56), P OR=0.025; ORProPro vs. ArgArg + ArgPro=1.74 (95 % CI, 1.14-2.66), P OR=0.010). Subgroup analyses by source of controls and hepatitis virus infection status further demonstrated the significant association, whereas stratification factors involving gender and family history of HCC did not modify the association between p53 codon 72 Arg/Pro polymorphism and HCC risk. This meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism may play a critical role in the development of HCC, and gender and family history of HCC may not modulate the effect of p53 codon 72 Arg/Pro in HCC risk.

  6. P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis.

    PubMed

    He, Fang; Xia, Yi; Liu, Huafeng; Li, Jin; Wang, Chao

    2013-10-01

    P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human chromosome 17p13. Many case-control studies have investigated the association between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided inconsistent findings. To better understand the pathogenesis of glioma, we performed the current meta-analysis by pooling data from all available individual studies. According to the inclusion criteria, ten independent publications with 11 case-control studies were included into this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no appreciable correlation was observed among the total studies in all gene models (ORPro allele vs. Arg allele = 1.04, 95 % CI = 0.90-1.20, P OR = 0.581; ORPro/Pro vs. Arg/Arg = 0.95, 95 % CI = 0.80-1.14, P OR = 0.614; ORPro/Arg vs. Arg/Arg = 1.01, 95 % CI = 0.79-1.29, P OR = 0.993; ORPro/Arg + Pro/Pro vs. Arg/Arg = 1.03, 95 % CI = 0.82-1.29, P OR = 0.799; ORPro/Pro vs. Arg/Arg + Pro/Arg = 1.02, 95 % CI = 0.86-1.22, P OR = 0.785). In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype seemed to be negatively associated with the glioma risk among patients with glioblastoma (ORPro/Pro vs. Arg/Arg = 0.68, 95 % CI = 0.48-0.95, P OR = 0.026). Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a protective role in the development of glioblastoma. The relationship of p53 codon 72 Arg/Pro polymorphism with the susceptibility to glioma needs further estimation by more individual studies with high quality across ethnicities.

  7. Expression of varied GFPs in Saccharomyces cerevisiae: codon optimization yields stronger than expected expression and fluorescence intensity

    PubMed Central

    Kaishima, Misato; Ishii, Jun; Matsuno, Toshihide; Fukuda, Nobuo; Kondo, Akihiko

    2016-01-01

    Green fluorescent protein (GFP), which was originally isolated from jellyfish, is a widely used tool in biological research, and homologs from other organisms are available. However, researchers must determine which GFP is the most suitable for a specific host. Here, we expressed GFPs from several sources in codon-optimized and non-codon-optimized forms in the yeast Saccharomyces cerevisiae, which represents an ideal eukaryotic model. Surprisingly, codon-optimized mWasabi and mNeonGreen, which are typically the brightest GFPs, emitted less green fluorescence than did the other five codon-optimized GFPs tested in S. cerevisiae. Further, commercially available GFPs that have been optimized for mammalian codon usage (e.g., EGFP, AcGFP1 and TagGFP2) unexpectedly exhibited extremely low expression levels in S. cerevisiae. In contrast, codon-optimization of the GFPs for S. cerevisiae markedly increased their expression levels, and the fluorescence intensity of the cells increased by a maximum of 101-fold. Among the tested GFPs, the codon-optimized monomeric mUkG1 from soft coral showed the highest levels of both expression and fluorescence. Finally, the expression of this protein as a fusion-tagged protein successfully improved the reporting system’s ability to sense signal transduction and protein–protein interactions in S. cerevisiae and increased the detection rates of target cells using flow cytometry. PMID:27782154

  8. Partially supervised P300 speller adaptation for eventual stimulus timing optimization: target confidence is superior to error-related potential score as an uncertain label

    NASA Astrophysics Data System (ADS)

    Zeyl, Timothy; Yin, Erwei; Keightley, Michelle; Chau, Tom

    2016-04-01

    Objective. Error-related potentials (ErrPs) have the potential to guide classifier adaptation in BCI spellers, for addressing non-stationary performance as well as for online optimization of system parameters, by providing imperfect or partial labels. However, the usefulness of ErrP-based labels for BCI adaptation has not been established in comparison to other partially supervised methods. Our objective is to make this comparison by retraining a two-step P300 speller on a subset of confident online trials using naïve labels taken from speller output, where confidence is determined either by (i) ErrP scores, (ii) posterior target scores derived from the P300 potential, or (iii) a hybrid of these scores. We further wish to evaluate the ability of partially supervised adaptation and retraining methods to adjust to a new stimulus-onset asynchrony (SOA), a necessary step towards online SOA optimization. Approach. Eleven consenting able-bodied adults attended three online spelling sessions on separate days with feedback in which SOAs were set at 160 ms (sessions 1 and 2) and 80 ms (session 3). A post hoc offline analysis and a simulated online analysis were performed on sessions two and three to compare multiple adaptation methods. Area under the curve (AUC) and symbols spelled per minute (SPM) were the primary outcome measures. Main results. Retraining using supervised labels confirmed improvements of 0.9 percentage points (session 2, p < 0.01) and 1.9 percentage points (session 3, p < 0.05) in AUC using same-day training data over using data from a previous day, which supports classifier adaptation in general. Significance. Using posterior target score alone as a confidence measure resulted in the highest SPM of the partially supervised methods, indicating that ErrPs are not necessary to boost the performance of partially supervised adaptive classification. Partial supervision significantly improved SPM at a novel SOA, showing promise for eventual online SOA

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

    PubMed

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

    2016-01-01

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

  10. Genetic variation in codons 167, 198 and 200 of the beta-tubulin gene in whipworms (Trichuris spp.) from a range of domestic animals and wildlife.

    PubMed

    Hansen, Tina V A; Nejsum, Peter; Olsen, Annette; Thamsborg, Stig Milan

    2013-03-31

    A recurrent problem in the control of whipworm (Trichuris spp.) infections in many animal species and man is the relatively low efficacy of treatment with a single application of benzimidazoles (BZs). The presence of single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 in the beta-tubulin gene has been associated with BZ anthelmintic resistance in intestinal nematodes of veterinary importance. We hypothesized that the low susceptibility to BZ could be related to a natural tolerance or induced resistance caused by BZ-resistant associated SNPs. The aim of the present study was therefore to investigate the presence of these SNPs in the beta-tubulin gene of Trichuris spp. obtained from a range of animals. DNA was extracted from a total of 121 Trichuris spp. adult whipworm specimens obtained from 6 different host species. The number of worms from each host was pig: 31, deer: 21, sheep: 18, mouse: 17, dog: 19 and Arabian camels: 14. A pooled sample of Trichuris eggs from 3 moose was also used. In order to amplify the beta-tubulin fragments which covered codons 167, 198 and 200 of the gene, degenerate primers were designed. The sequences obtained were used to design species specific primers and used to amplify a ~476 bp fragment of the beta-tubulin gene. The PCR products were sequenced, analysed and evaluated. We did not identify SNPs in codons 167, 198 or 200 that led to amino acid substitutions in any of the studied Trichuris spp., but genetic variation expected to be related to species differences was observed. The cluster analysis showed close evolutionary relationship between Trichuris spp. from ruminants and between mouse and dog whereas the pig-derived worms, T. suis, clustered with T. trichiura obtained from Genbank.

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

    PubMed Central

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

    1982-01-01

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

  12. Development of the genetic code: insights from a fungal codon reassignment.

    PubMed

    Moura, Gabriela R; Paredes, João A; Santos, Manuel A S

    2010-01-21

    The high conservation of the genetic code and its fundamental role in genome decoding suggest that its evolution is highly restricted or even frozen. However, various prokaryotic and eukaryotic genetic code alterations, several alternative tRNA-dependent amino acid biosynthesis pathways, regulation of tRNA decoding by diverse nucleoside modifications and recent in vivo incorporation of non-natural amino acids into prokaryotic and eukaryotic proteins, show that the code evolves and is surprisingly flexible. The cellular mechanisms and the proteome buffering capacity that support such evolutionary processes remain unclear. Here we explore the hypothesis that codon misreading and reassignment played fundamental roles in the development of the genetic code and we show how a fungal codon reassignment is enlightening its evolution.

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

    SciTech Connect

    Celi, F.S.; Silver, K.; Walston, J.

    1995-09-01

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

  14. Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life.

    PubMed Central

    Belgrader, P; Cheng, J; Zhou, X; Stephenson, L S; Maquat, L E

    1994-01-01

    Frameshift and nonsense mutations within the gene for human triosephosphate isomerase (TPI) that generate a nonsense codon within the first three-fourths of the protein coding region have been found to reduce the abundance of the product mRNA that copurifies with nuclei. The cellular process and location of the nonsense codon-mediated reduction have proven difficult to elucidate for technical reasons. We show here, using electron microscopy to judge the purity of isolated nuclei, that the previously established reduction to 25% of the normal mRNA level is evident for nuclei that are free of detectable cytoplasmic contamination. Therefore, the reduction is likely to be characteristic of bona fide nuclear RNA. Fully spliced nuclear mRNA is identified by Northern (RNA) blot hybridization and a reverse transcription-PCR assay as the species that undergoes decay in experiments that used the human c-fos promoter to elicit a burst and subsequent shutoff of TPI gene transcription upon the addition of serum to serum-deprived cells. Finally, the finding that deletion of a 5' splice site of the TPI gene results predominantly but not exclusively in the removal by splicing (i.e., skipping) of the upstream exon as a part of the flanking introns has been used to demonstrate that decay is specific to those mRNA products that maintain the nonsense codon. This result, together with our previous results that implicate translation by ribosomes and charged tRNAs in the decay mechanism, indicate that nonsense codon recognition takes place after splicing and triggers decay solely in cis. The possibility that decay takes place during the process of mRNA export from the nucleus to the cytoplasm is discussed. Images PMID:7969159

  15. [Genetic code: codon bases--the symbols of amino acid synthesis and catabolism pathways].

    PubMed

    Konyshev, V A

    1983-01-01

    The correlations between genetic codes of amino acids and pathways of synthesis and catabolism of carbon backbone of amino acids are considered. Codes of amino acids which are synthesized from oxoacids of glycolysis, the Krebs cycle and glyoxalic cycle via transamination without any additional chemical reactions, are initiated with guanine (alanine, glutamic and aspartic acids, glycine). Codons of amino acids which are formed on the branches of glycolysis at the level of compounds with three carbon atoms, begin with uracil (phenylalanine, serine, leucine, tyrosine, cysteine, tryptophan). Codes of amino acids formed from aspartate begin with adenine (methionine, isoleucine, threonine, asparagine, lysine, serine), while those of the amino acids formed from the compounds with five carbon atoms (glutamic acid and phosphoribosyl pyrophosphate) begin with cytosine (arginine, proline, glutamine, histidine). The second letter of codons is linked to catabolic pathways of amino acids: most of amino acids entering glycolysis and the Krebs cycle through even-numbered carbon compounds, have adenine and uracil at the second position of codes (A-U type); most of amino acids entering the glycolysis and the Krebs cycle via odd-numbered carbon compounds, have codons with guanine and cytidine at the second position (G-C type). The usage of purine and pyrimidine as the third letter of weak codones in most of amino acids is linked to the enthropy of amino acid formation. A hypothesis claiming that the linear genetic code was assembled from the purine and pyrimidine derivatives which have acted as participants of primitive control of amino acid synthesis and catabolism, is suggested.

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

    PubMed

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

    2013-09-01

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

  17. Hepatocellular carcinoma p53 G > T transversions at codon 249: the fingerprint of aflatoxin exposure?

    PubMed

    Lasky, T; Magder, L

    1997-04-01

    The molecular epidemiology of p53 mutations allows the possibility of correlating particular mutations with specific environmental carcinogens and establishing one step in the causal pathway between exposure to carcinogens and the development of cancer. A striking example is the G > T transversion at the third base pair of codon 249 observed in liver cancer patients possibly exposed to high levels of aflatoxins in their agricultural products. In this paper, we describe a systematic review of the literature and access the quality of the available data. We found methodologic limitations in the studies. In particular, the key independent variable, aflatoxin exposure, was not assessed in these studies, with the exception of one study that measured a marker of exposure. Instead, nationality, geographic residence, or geographic site of hospital were used as surrogate markers for exposure. Patients from areas with high aflatoxin levels were more likely to have p53 mutations than were patients from areas with low aflatoxin levels. In the group with p53 mutations, patients from areas with high aflatoxin levels had higher proportions of mutations with codon 249 G > T transversions. The differences in proportions with p53 mutations were significant, as were the differences in proportions of codon 249 G > T transversions among patients with p53 mutations. Aflatoxin may increase the proportion of p53 mutations by causing a single mutation, the codon 249 G > T transversion, thus explaining some of the excess liver cancer associated with aflatoxin exposure. However, it is premature to conclude that p53 mutations are established markers for environmental carcinogens.

  18. Non-AUG start codons responsible for ABO weak blood group alleles on initiation mutant backgrounds

    PubMed Central

    Cid, Emili; Yamamoto, Miyako; Yamamoto, Fumiichiro

    2017-01-01

    Histo-blood group ABO gene polymorphism is crucial in transfusion medicine. We studied the activity and subcellular distribution of ABO gene-encoded A glycosyltransferases with N-terminal truncation. We hypothesized that truncated enzymes starting at internal methionines drove the synthesis of oligosaccharide A antigen in those already described alleles that lack a proper translation initiation codon. Not only we tested the functionality of the mutant transferases by expressing them and assessing their capacity to drive the appearance of A antigen on the cell surface, but we also analyzed their subcellullar localization, which has not been described before. The results highlight the importance of the transmembrane domain because proteins deprived of it are not able to localize properly and deliver substantial amounts of antigen on the cell surface. Truncated proteins with their first amino acid well within the luminal domain are not properly localized and lose their enzymatic activity. Most importantly, we demonstrated that other codons than AUG might be used to start the protein synthesis rather than internal methionines in translation-initiation mutants, explaining the molecular mechanism by which transferases lacking a classical start codon are able to synthesize A/B antigens. PMID:28139731

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