Sample records for strong positive selection

  1. Conditional entropy in variation-adjusted windows detects selection signatures associated with expression quantitative trait loci (eQTLs)

    PubMed Central

    2015-01-01

    Background Over the past 50,000 years, shifts in human-environmental or human-human interactions shaped genetic differences within and among human populations, including variants under positive selection. Shaped by environmental factors, such variants influence the genetics of modern health, disease, and treatment outcome. Because evolutionary processes tend to act on gene regulation, we test whether regulatory variants are under positive selection. We introduce a new approach to enhance detection of genetic markers undergoing positive selection, using conditional entropy to capture recent local selection signals. Results We use conditional logistic regression to compare our Adjusted Haplotype Conditional Entropy (H|H) measure of positive selection to existing positive selection measures. H|H and existing measures were applied to published regulatory variants acting in cis (cis-eQTLs), with conditional logistic regression testing whether regulatory variants undergo stronger positive selection than the surrounding gene. These cis-eQTLs were drawn from six independent studies of genotype and RNA expression. The conditional logistic regression shows that, overall, H|H is substantially more powerful than existing positive-selection methods in identifying cis-eQTLs against other Single Nucleotide Polymorphisms (SNPs) in the same genes. When broken down by Gene Ontology, H|H predictions are particularly strong in some biological process categories, where regulatory variants are under strong positive selection compared to the bulk of the gene, distinct from those GO categories under overall positive selection. . However, cis-eQTLs in a second group of genes lack positive selection signatures detectable by H|H, consistent with ancient short haplotypes compared to the surrounding gene (for example, in innate immunity GO:0042742); under such other modes of selection, H|H would not be expected to be a strong predictor.. These conditional logistic regression models are adjusted for Minor allele frequency(MAF); otherwise, ascertainment bias is a huge factor in all eQTL data sets. Relationships between Gene Ontology categories, positive selection and eQTL specificity were replicated with H|H in a single larger data set. Our measure, Adjusted Haplotype Conditional Entropy (H|H), was essential in generating all of the results above because it: 1) is a stronger overall predictor for eQTLs than comparable existing approaches, and 2) shows low sequential auto-correlation, overcoming problems with convergence of these conditional regression statistical models. Conclusions Our new method, H|H, provides a consistently more robust signal associated with cis-eQTLs compared to existing methods. We interpret this to indicate that some cis-eQTLs are under positive selection compared to their surrounding genes. Conditional entropy indicative of a selective sweep is an especially strong predictor of eQTLs for genes in several biological processes of medical interest. Where conditional entropy is a weak or negative predictor of eQTLs, such as innate immune genes, this would be consistent with balancing selection acting on such eQTLs over long time periods. Different measures of selection may be needed for variant prioritization under other modes of evolutionary selection. PMID:26111110

  2. Strong Purifying Selection at Synonymous Sites in D. melanogaster

    PubMed Central

    Lawrie, David S.; Messer, Philipp W.; Hershberg, Ruth; Petrov, Dmitri A.

    2013-01-01

    Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data to show that, contrary to this expectation, 22% of four-fold synonymous (4D) sites in Drosophila melanogaster evolve under very strong selective constraint while few, if any, appear to be under weak constraint. Linking polymorphism with divergence data, we further find that the fraction of synonymous sites exposed to strong purifying selection is higher for those positions that show slower evolution on the Drosophila phylogeny. The function underlying the inferred strong constraint appears to be separate from splicing enhancers, nucleosome positioning, and the translational optimization generating canonical codon bias. The fraction of synonymous sites under strong constraint within a gene correlates well with gene expression, particularly in the mid-late embryo, pupae, and adult developmental stages. Genes enriched in strongly constrained synonymous sites tend to be particularly functionally important and are often involved in key developmental pathways. Given that the observed widespread constraint acting on synonymous sites is likely not limited to Drosophila, the role of synonymous sites in genetic disease and adaptation should be reevaluated. PMID:23737754

  3. Long-range transcriptional interference in E. coli used to construct a dual positive selection system for genetic switches

    PubMed Central

    Hoffmann, Stefan A.; Kruse, Sabrina M.; Arndt, Katja M.

    2016-01-01

    Abstract We have investigated transcriptional interference between convergent genes in E. coli and demonstrate substantial interference for inter-promoter distances of as far as 3 kb. Interference can be elicited by both strong σ70 dependent and T7 promoters. In the presented design, a strong promoter driving gene expression of a ‘forward’ gene interferes with the expression of a ‘reverse’ gene by a weak promoter. This arrangement allows inversely correlated gene expression without requiring further regulatory components. Thus, modulation of the activity of the strong promoter alters expression of both the forward and the reverse gene. We used this design to develop a dual selection system for conditional operator site binding, allowing positive selection both for binding and for non-binding to DNA. This study demonstrates the utility of this novel system using the Lac repressor as a model protein for conditional DNA binding, and spectinomycin and chloramphenicol resistance genes as positive selection markers in liquid culture. Randomized LacI libraries were created and subjected to subsequent dual selection, but mispairing IPTG and selection cues in respect to the wild-type LacI response, allowing the isolation of a LacI variant with a reversed IPTG response within three rounds of library generation and dual selection. PMID:26932362

  4. The effect of sexual selection on adaptation and extinction under increasing temperatures.

    PubMed

    Parrett, Jonathan M; Knell, Robert J

    2018-04-25

    Strong sexual selection has been reported to both enhance and hinder the adaptive capacity and persistence of populations when exposed to novel environments. Consequently, how sexual selection influences population adaption and persistence under stress remains widely debated. Here, we present two empirical investigations of the fitness consequences of sexual selection on populations of the Indian meal moth, Plodia interpunctella, exposed to stable or gradually increasing temperatures. When faced with increasing temperatures, strong sexual selection was associated with both increased fecundity and offspring survival compared with populations experiencing weak sexual selection, suggesting sexual selection acts to drive adaptive evolution by favouring beneficial alleles. Strong sexual selection did not, however, delay extinction when the temperature became excessively high. By manipulating individuals' mating opportunities during fitness assays, we were able to assess the effect of multiple mating independently from the effect of population-level sexual selection, and found that polyandry has a positive effect on both fecundity and offspring survival under increasing temperatures in those populations evolving with weak sexual selection. Within stable temperatures, there were some benefits from strong sexual selection but these were not consistent across the entire experiment, possibly reflecting changing costs and benefits of sexual selection under stabilizing and directional selection. These results indicate that sexual selection can provide a buffer against climate change and increase adaptation rates within a continuously changing environment. These positive effects of sexual selection may, however, be too small to protect populations and delay extinction when environmental changes are relatively rapid. © 2018 The Author(s).

  5. Statistical and molecular analyses of evolutionary significance of red-green color vision and color blindness in vertebrates.

    PubMed

    Yokoyama, Shozo; Takenaka, Naomi

    2005-04-01

    Red-green color vision is strongly suspected to enhance the survival of its possessors. Despite being red-green color blind, however, many species have successfully competed in nature, which brings into question the evolutionary advantage of achieving red-green color vision. Here, we propose a new method of identifying positive selection at individual amino acid sites with the premise that if positive Darwinian selection has driven the evolution of the protein under consideration, then it should be found mostly at the branches in the phylogenetic tree where its function had changed. The statistical and molecular methods have been applied to 29 visual pigments with the wavelengths of maximal absorption at approximately 510-540 nm (green- or middle wavelength-sensitive [MWS] pigments) and at approximately 560 nm (red- or long wavelength-sensitive [LWS] pigments), which are sampled from a diverse range of vertebrate species. The results show that the MWS pigments are positively selected through amino acid replacements S180A, Y277F, and T285A and that the LWS pigments have been subjected to strong evolutionary conservation. The fact that these positively selected M/LWS pigments are found not only in animals with red-green color vision but also in those with red-green color blindness strongly suggests that both red-green color vision and color blindness have undergone adaptive evolution independently in different species.

  6. Pollen-specific, but not sperm-specific, genes show stronger purifying selection and higher rates of positive selection than sporophytic genes in Capsella grandiflora.

    PubMed

    Arunkumar, Ramesh; Josephs, Emily B; Williamson, Robert J; Wright, Stephen I

    2013-11-01

    Selection on the gametophyte can be a major force shaping plant genomes as 7-11% of genes are expressed only in that phase and 60% of genes are expressed in both the gametophytic and sporophytic phases. The efficacy of selection on gametophytic tissues is likely to be influenced by sexual selection acting on male and female functions of hermaphroditic plants. Moreover, the haploid nature of the gametophytic phase allows selection to be efficient in removing recessive deleterious mutations and fixing recessive beneficial mutations. To assess the importance of gametophytic selection, we compared the strength of purifying selection and extent of positive selection on gametophyte- and sporophyte-specific genes in the highly outcrossing plant Capsella grandiflora. We found that pollen-exclusive genes had a larger fraction of sites under strong purifying selection, a greater proportion of adaptive substitutions, and faster protein evolution compared with seedling-exclusive genes. In contrast, sperm cell-exclusive genes had a smaller fraction of sites under strong purifying selection, a lower proportion of adaptive substitutions, and slower protein evolution compared with seedling-exclusive genes. Observations of strong selection acting on pollen-expressed genes are likely explained by sexual selection resulting from pollen competition aided by the haploid nature of that tissue. The relaxation of selection in sperm might be due to the reduced influence of intrasexual competition, but reduced gene expression may also be playing an important role.

  7. Choices between positive and negative reinforcement during treatment for escape-maintained behavior.

    PubMed

    DeLeon, I G; Neidert, P L; Anders, B M; Rodriguez-Catter, V

    2001-01-01

    Positive reinforcement was more effective than negative reinforcement in promoting compliance and reducing escape-maintained problem behavior for a child with autism. Escape extinction was then added while the child was given a choice between positive or negative reinforcement for compliance and the reinforcement schedule was thinned. When the reinforcement requirement reached 10 consecutive tasks, the treatment effects became inconsistent and reinforcer selection shifted from a strong preference for positive reinforcement to an unstable selection pattern.

  8. Limited Evidence for Classic Selective Sweeps in African Populations

    PubMed Central

    Granka, Julie M.; Henn, Brenna M.; Gignoux, Christopher R.; Kidd, Jeffrey M.; Bustamante, Carlos D.; Feldman, Marcus W.

    2012-01-01

    While hundreds of loci have been identified as reflecting strong-positive selection in human populations, connections between candidate loci and specific selective pressures often remain obscure. This study investigates broader patterns of selection in African populations, which are underrepresented despite their potential to offer key insights into human adaptation. We scan for hard selective sweeps using several haplotype and allele-frequency statistics with a data set of nearly 500,000 genome-wide single-nucleotide polymorphisms in 12 highly diverged African populations that span a range of environments and subsistence strategies. We find that positive selection does not appear to be a strong determinant of allele-frequency differentiation among these African populations. Haplotype statistics do identify putatively selected regions that are shared across African populations. However, as assessed by extensive simulations, patterns of haplotype sharing between African populations follow neutral expectations and suggest that tails of the empirical distributions contain false-positive signals. After highlighting several genomic regions where positive selection can be inferred with higher confidence, we use a novel method to identify biological functions enriched among populations’ empirical tail genomic windows, such as immune response in agricultural groups. In general, however, it seems that current methods for selection scans are poorly suited to populations that, like the African populations in this study, are affected by ascertainment bias and have low levels of linkage disequilibrium, possibly old selective sweeps, and potentially reduced phasing accuracy. Additionally, population history can confound the interpretation of selection statistics, suggesting that greater care is needed in attributing broad genetic patterns to human adaptation. PMID:22960214

  9. Retinal transcriptome sequencing sheds light on the adaptation to nocturnal and diurnal lifestyles in raptors.

    PubMed

    Wu, Yonghua; Hadly, Elizabeth A; Teng, Wenjia; Hao, Yuyang; Liang, Wei; Liu, Yu; Wang, Haitao

    2016-09-20

    Owls (Strigiformes) represent a fascinating group of birds that are the ecological night-time counterparts to diurnal raptors (Accipitriformes). The nocturnality of owls, unusual within birds, has favored an exceptional visual system that is highly tuned for hunting at night, yet the molecular basis for this adaptation is lacking. Here, using a comparative evolutionary analysis of 120 vision genes obtained by retinal transcriptome sequencing, we found strong positive selection for low-light vision genes in owls, which contributes to their remarkable nocturnal vision. Not surprisingly, we detected gene loss of the violet/ultraviolet-sensitive opsin (SWS1) in all owls we studied, but two other color vision genes, the red-sensitive LWS and the blue-sensitive SWS2, were found to be under strong positive selection, which may be linked to the spectral tunings of these genes toward maximizing photon absorption in crepuscular conditions. We also detected the only other positively selected genes associated with motion detection in falcons and positively selected genes associated with bright-light vision and eye protection in other diurnal raptors (Accipitriformes). Our results suggest the adaptive evolution of vision genes reflect differentiated activity time and distinct hunting behaviors.

  10. Retinal transcriptome sequencing sheds light on the adaptation to nocturnal and diurnal lifestyles in raptors

    PubMed Central

    Wu, Yonghua; Hadly, Elizabeth A.; Teng, Wenjia; Hao, Yuyang; Liang, Wei; Liu, Yu; Wang, Haitao

    2016-01-01

    Owls (Strigiformes) represent a fascinating group of birds that are the ecological night-time counterparts to diurnal raptors (Accipitriformes). The nocturnality of owls, unusual within birds, has favored an exceptional visual system that is highly tuned for hunting at night, yet the molecular basis for this adaptation is lacking. Here, using a comparative evolutionary analysis of 120 vision genes obtained by retinal transcriptome sequencing, we found strong positive selection for low-light vision genes in owls, which contributes to their remarkable nocturnal vision. Not surprisingly, we detected gene loss of the violet/ultraviolet-sensitive opsin (SWS1) in all owls we studied, but two other color vision genes, the red-sensitive LWS and the blue-sensitive SWS2, were found to be under strong positive selection, which may be linked to the spectral tunings of these genes toward maximizing photon absorption in crepuscular conditions. We also detected the only other positively selected genes associated with motion detection in falcons and positively selected genes associated with bright-light vision and eye protection in other diurnal raptors (Accipitriformes). Our results suggest the adaptive evolution of vision genes reflect differentiated activity time and distinct hunting behaviors. PMID:27645106

  11. Ratings for emotion film clips.

    PubMed

    Gabert-Quillen, Crystal A; Bartolini, Ellen E; Abravanel, Benjamin T; Sanislow, Charles A

    2015-09-01

    Film clips are widely utilized to elicit emotion in a variety of research studies. Normative ratings for scenes selected for these purposes support the idea that selected clips correspond to the intended target emotion, but studies reporting normative ratings are limited. Using an ethnically diverse sample of college undergraduates, selected clips were rated for intensity, discreteness, valence, and arousal. Variables hypothesized to affect the perception of stimuli (i.e., gender, race-ethnicity, and familiarity) were also examined. Our analyses generally indicated that males reacted strongly to positively valenced film clips, whereas females reacted more strongly to negatively valenced film clips. Caucasian participants tended to react more strongly to the film clips, and we found some variation by race-ethnicity across target emotions. Finally, familiarity with the films tended to produce higher ratings for positively valenced film clips, and lower ratings for negatively valenced film clips. These findings provide normative ratings for a useful set of film clips for the study of emotion, and they underscore factors to be considered in research that utilizes scenes from film for emotion elicitation.

  12. Positive selection of AS3MT to arsenic water in Andean populations

    PubMed Central

    Eichstaedt, Christina A.; Antao, Tiago; Cardona, Alexia; Pagani, Luca; Kivisild, Toomas; Mormina, Maru

    2016-01-01

    Arsenic is a carcinogen associated with skin lesions and cardiovascular diseases. The Colla population from the Puna region in Northwest Argentinean is exposed to levels of arsenic in drinking water exceeding the recommended maximum by a factor of 20. Yet, they thrive in this challenging environment since thousands of years and therefore we hypothesize strong selection signatures in genes involved in arsenic metabolism. We analyzed genome-wide genotype data for 730,000 loci in 25 Collas, considering 24 individuals of the neighbouring Calchaquíes and 24 Wichí from the Gran Chaco region in the Argentine province of Salta as control groups. We identified a strong signal of positive selection in the main arsenic methyltransferase AS3MT gene, which has been previously associated with lower concentrations of the most toxic product of arsenic metabolism monomethylarsonic acid. This study confirms recent studies reporting selection signals in the AS3MT gene albeit using different samples, tests and control populations. PMID:26366667

  13. Genome-wide signals of positive selection in human evolution

    PubMed Central

    Enard, David; Messer, Philipp W.; Petrov, Dmitri A.

    2014-01-01

    The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes. PMID:24619126

  14. Genomic signatures of positive selection in humans and the limits of outlier approaches.

    PubMed

    Kelley, Joanna L; Madeoy, Jennifer; Calhoun, John C; Swanson, Willie; Akey, Joshua M

    2006-08-01

    Identifying regions of the human genome that have been targets of positive selection will provide important insights into recent human evolutionary history and may facilitate the search for complex disease genes. However, the confounding effects of population demographic history and selection on patterns of genetic variation complicate inferences of selection when a small number of loci are studied. To this end, identifying outlier loci from empirical genome-wide distributions of genetic variation is a promising strategy to detect targets of selection. Here, we evaluate the power and efficiency of a simple outlier approach and describe a genome-wide scan for positive selection using a dense catalog of 1.58 million SNPs that were genotyped in three human populations. In total, we analyzed 14,589 genes, 385 of which possess patterns of genetic variation consistent with the hypothesis of positive selection. Furthermore, several extended genomic regions were found, spanning >500 kb, that contained multiple contiguous candidate selection genes. More generally, these data provide important practical insights into the limits of outlier approaches in genome-wide scans for selection, provide strong candidate selection genes to study in greater detail, and may have important implications for disease related research.

  15. Selective Migration among Southern Blacks: A Reinterpretation of Lee (1951).

    ERIC Educational Resources Information Center

    Wolff, JosePh L.

    1979-01-01

    Explanations of differences in IQs of Northern and Southern Blacks focus on selective migration (hereditarians) or environmental causes such as education, discrimination and cultural deprivation. In this paper the environmentalist position is questioned and certain neglected features of Lee's data are construed as providing strong evidence for…

  16. Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

    PubMed Central

    Machkovech, Heather M.; Bedford, Trevor; Suchard, Marc A.

    2015-01-01

    ABSTRACT Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. IMPORTANCE There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+ T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the “trunk” of the phylogenetic tree. Overall, our results show that CD8+ T cells targeting nucleoprotein play an important role in shaping influenza virus evolution. PMID:26311880

  17. Immediate movement history influences reach-to-grasp action selection in children and adults.

    PubMed

    Kent, Samuel W; Wilson, Andrew D; Plumb, Mandy S; Williams, Justin H G; Mon-Williams, Mark

    2009-01-01

    Action selection is subject to many biases. Immediate movement history is one such bias seen in young infants. Is this bias strong enough to affect adult behavior? Adult participants reached and grasped a cylinder positioned to require either pronation or supination of the hand. Successive cylinder positions changed either randomly or systematically between trials. Random positioning led to optimized economy of movement. In contrast, systematic changes in position biased action selection toward previously selected actions at the expense of movement economy. Thus, one switches to a new movement only when the savings outweigh the costs of the switch. Immediate movement history had an even larger influence on children aged 7-15 years. This suggests that switching costs are greater in children, which is consistent with their reduced grasping experience. The presence of this effect in adults suggests that immediate movement history exerts a more widespread and pervasive influence on patterns of action selection than researchers had previously recognized.

  18. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.

    PubMed

    Janova, Eva; Matiasovic, Jan; Vahala, Jiri; Vodicka, Roman; Van Dyk, Enette; Horin, Petr

    2009-07-01

    The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

  19. Weak Negative and Positive Selection and the Drift Load at Splice Sites

    PubMed Central

    Denisov, Stepan V.; Bazykin, Georgii A.; Sutormin, Roman; Favorov, Alexander V.; Mironov, Andrey A.; Gelfand, Mikhail S.; Kondrashov, Alexey S.

    2014-01-01

    Splice sites (SSs) are short sequences that are crucial for proper mRNA splicing in eukaryotic cells, and therefore can be expected to be shaped by strong selection. Nevertheless, in mammals and in other intron-rich organisms, many of the SSs often involve nonconsensus (Nc), rather than consensus (Cn), nucleotides, and beyond the two critical nucleotides, the SSs are not perfectly conserved between species. Here, we compare the SS sequences between primates, and between Drosophila fruit flies, to reveal the pattern of selection acting at SSs. Cn-to-Nc substitutions are less frequent, and Nc-to-Cn substitutions are more frequent, than neutrally expected, indicating, respectively, negative and positive selection. This selection is relatively weak (1 < |4Nes| < 4), and has a similar efficiency in primates and in Drosophila. Within some nucleotide positions, the positive selection in favor of Nc-to-Cn substitutions is weaker than the negative selection maintaining already established Cn nucleotides; this difference is due to site-specific negative selection favoring current Nc nucleotides. In general, however, the strength of negative selection protecting the Cn alleles is similar in magnitude to the strength of positive selection favoring replacement of Nc alleles, as expected under the simple nearly neutral turnover. In summary, although a fraction of the Nc nucleotides within SSs is maintained by selection, the abundance of deleterious nucleotides in this class suggests a substantial genome-wide drift load. PMID:24966225

  20. A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish

    PubMed Central

    van der Aa, Lieke M; Levraud, Jean-Pierre; Yahmi, Malika; Lauret, Emilie; Briolat, Valérie; Herbomel, Philippe; Benmansour, Abdenour; Boudinot, Pierre

    2009-01-01

    Background In mammals, the members of the tripartite motif (TRIM) protein family are involved in various cellular processes including innate immunity against viral infection. Viruses exert strong selective pressures on the defense system. Accordingly, antiviral TRIMs have diversified highly through gene expansion, positive selection and alternative splicing. Characterizing immune TRIMs in other vertebrates may enlighten their complex evolution. Results We describe here a large new subfamily of TRIMs in teleosts, called finTRIMs, identified in rainbow trout as virus-induced transcripts. FinTRIMs are formed of nearly identical RING/B-box regions and C-termini of variable length; the long variants include a B30.2 domain. The zebrafish genome harbors a striking diversity of finTRIMs, with 84 genes distributed in clusters on different chromosomes. A phylogenetic analysis revealed different subsets suggesting lineage-specific diversification events. Accordingly, the number of fintrim genes varies greatly among fish species. Conserved syntenies were observed only for the oldest fintrims. The closest mammalian relatives are trim16 and trim25, but they are not true orthologs. The B30.2 domain of zebrafish finTRIMs evolved under strong positive selection. The positions under positive selection are remarkably congruent in finTRIMs and in mammalian antiviral TRIM5α, concentrated within a viral recognition motif in mammals. The B30.2 domains most closely related to finTRIM are found among NOD-like receptors (NLR), indicating that the evolution of TRIMs and NLRs was intertwined by exon shuffling. Conclusion The diversity, evolution, and features of finTRIMs suggest an important role in fish innate immunity; this would make them the first TRIMs involved in immunity identified outside mammals. PMID:19196451

  1. Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

    PubMed Central

    2015-01-01

    Background It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. Results Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. Conclusions The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates. PMID:26449467

  2. FOXP2 Targets Show Evidence of Positive Selection in European Populations

    PubMed Central

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C.; Fisher, Simon E.; Tyler-Smith, Chris

    2013-01-01

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

  3. Evaluation of Relationships Between Reported Resilience and Soldier Outcomes. Report Number 2: Positive Performance Outcomes in Officers (Promotions, Selections, & Professions)

    DTIC Science & Technology

    2011-04-01

    Schaufeli , Leiter, & Taris, 2008), as well as individual values and personality (Thomas, Dickson, & Bliese, 2001). In addition to the research on...psychological health. STRONG MINDS STRONG BODIES 21 References Bakker, A.B., Schaufeli , W.B., Leiter, M.P., & Taris, T.W. (2008). Work engagement: An

  4. Strongly-motivated positive affects induce faster responses to local than global information of visual stimuli: an approach using large-size Navon letters.

    PubMed

    Noguchi, Yasuki; Tomoike, Kouta

    2016-01-12

    Recent studies argue that strongly-motivated positive emotions (e.g. desire) narrow a scope of attention. This argument is mainly based on an observation that, while humans normally respond faster to global than local information of a visual stimulus (global advantage), positive affects eliminated the global advantage by selectively speeding responses to local (but not global) information. In other words, narrowing of attentional scope was indirectly evidenced by the elimination of global advantage (the same speed of processing between global and local information). No study has directly shown that strongly-motivated positive affects induce faster responses to local than global information while excluding a bias for global information (global advantage) in a baseline (emotionally-neutral) condition. In the present study, we addressed this issue by eliminating the global advantage in a baseline (neutral) state. Induction of positive affects under this state resulted in faster responses to local than global information. Our results provided direct evidence that positive affects in high motivational intensity narrow a scope of attention.

  5. Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages.

    PubMed

    Machkovech, Heather M; Bedford, Trevor; Suchard, Marc A; Bloom, Jesse D

    2015-11-01

    Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a novel computational approach to test for selection in CD8(+) T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8(+) T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8(+) T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8(+) T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the "trunk" of the phylogenetic tree. Overall, our results show that CD8(+) T cells targeting nucleoprotein play an important role in shaping influenza virus evolution. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Population genomics of the honey bee reveals strong signatures of positive selection on worker traits.

    PubMed

    Harpur, Brock A; Kent, Clement F; Molodtsova, Daria; Lebon, Jonathan M D; Alqarni, Abdulaziz S; Owayss, Ayman A; Zayed, Amro

    2014-02-18

    Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees.

  7. Population genomics of the honey bee reveals strong signatures of positive selection on worker traits

    PubMed Central

    Harpur, Brock A.; Kent, Clement F.; Molodtsova, Daria; Lebon, Jonathan M. D.; Alqarni, Abdulaziz S.; Owayss, Ayman A.; Zayed, Amro

    2014-01-01

    Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees. PMID:24488971

  8. Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species.

    PubMed

    Harrisson, K; Pavlova, A; Gan, H M; Lee, Y P; Austin, C M; Sunnucks, P

    2016-06-01

    Climatic differences across a taxon's range may be associated with specific bioenergetic demands and may result in genetics-based metabolic adaptation, particularly in aquatic ectothermic organisms that rely on heat exchange with the environment to regulate key physiological processes. Extending down the east coast of Australia, the Great Dividing Range (GDR) has a strong influence on climate and the evolutionary history of freshwater fish species. Despite the GDR acting as a strong contemporary barrier to fish movement, many species, and species with shared ancestries, are found on both sides of the GDR, indicative of historical dispersal events. We sequenced complete mitogenomes from the four extant species of the freshwater cod genus Maccullochella, two of which occur on the semi-arid, inland side of the GDR, and two on the mesic coastal side. We constructed a dated phylogeny and explored the relative influences of purifying and positive selection in the evolution of mitogenome divergence among species. Results supported mid- to late-Pleistocene divergence of Maccullochella across the GDR (220-710 thousand years ago), bringing forward previously reported dates. Against a background of pervasive purifying selection, we detected potentially functionally relevant fixed amino acid differences across the GDR. Although many amino acid differences between inland and coastal species may have become fixed under relaxed purifying selection in coastal environments rather than positive selection, there was evidence of episodic positive selection acting on specific codons in the Mary River coastal lineage, which has consistently experienced the warmest and least extreme climate in the genus.

  9. FOXP2 targets show evidence of positive selection in European populations.

    PubMed

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

    2013-05-02

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species

    PubMed Central

    Harrisson, K; Pavlova, A; Gan, H M; Lee, Y P; Austin, C M; Sunnucks, P

    2016-01-01

    Climatic differences across a taxon's range may be associated with specific bioenergetic demands and may result in genetics-based metabolic adaptation, particularly in aquatic ectothermic organisms that rely on heat exchange with the environment to regulate key physiological processes. Extending down the east coast of Australia, the Great Dividing Range (GDR) has a strong influence on climate and the evolutionary history of freshwater fish species. Despite the GDR acting as a strong contemporary barrier to fish movement, many species, and species with shared ancestries, are found on both sides of the GDR, indicative of historical dispersal events. We sequenced complete mitogenomes from the four extant species of the freshwater cod genus Maccullochella, two of which occur on the semi-arid, inland side of the GDR, and two on the mesic coastal side. We constructed a dated phylogeny and explored the relative influences of purifying and positive selection in the evolution of mitogenome divergence among species. Results supported mid- to late-Pleistocene divergence of Maccullochella across the GDR (220–710 thousand years ago), bringing forward previously reported dates. Against a background of pervasive purifying selection, we detected potentially functionally relevant fixed amino acid differences across the GDR. Although many amino acid differences between inland and coastal species may have become fixed under relaxed purifying selection in coastal environments rather than positive selection, there was evidence of episodic positive selection acting on specific codons in the Mary River coastal lineage, which has consistently experienced the warmest and least extreme climate in the genus. PMID:26883183

  11. The complexity of selection at the major primate beta-defensin locus.

    PubMed

    Semple, Colin A M; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

    2005-05-18

    We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Identification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

  12. Genetic dissection of adaptive form and function in rapidly speciating cichlid fishes.

    PubMed

    Henning, Frederico; Machado-Schiaffino, Gonzalo; Baumgarten, Lukas; Meyer, Axel

    2017-05-01

    Genes of major phenotypic effects and strong genetic correlations can facilitate adaptation, direct selective responses, and potentially lead to phenotypic convergence. However, the preponderance of this type of genetic architecture in repeatedly evolved adaptations remains unknown. Using hybrids between Haplochromis chilotes (thick-lipped) and Pundamilia nyererei (thin-lipped) we investigated the genetics underlying hypertrophied lips and elongated heads, traits that evolved repeatedly in cichlids. At least 25 loci of small-to-moderate and mainly additive effects were detected. Phenotypic variation in lip and head morphology was largely independent. Although several QTL overlapped for lip and head morphology traits, they were often of opposite effects. The distribution of effect signs suggests strong selection on lips. The fitness implications of several detected loci were demonstrated using a laboratory assay testing for the association between genotype and variation in foraging performance. The persistence of low fitness alleles in head morphology appears to be maintained through antagonistic pleiotropy/close linkage with positive-effect lip morphology alleles. Rather than being based on few major loci with strong positive genetic correlations, our results indicate that the evolution of the Lake Victoria thick-lipped ecomorph is the result of selection on numerous loci distributed throughout the genome. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  13. Dynamic Convergent Evolution Drives the Passage Adaptation across 48 Years' History of H3N2 Influenza Evolution.

    PubMed

    Chen, Hui; Deng, Qiang; Ng, Sock Hoon; Lee, Raphael Tze Chuen; Maurer-Stroh, Sebastian; Zhai, Weiwei

    2016-12-01

    Influenza viruses are often propagated in a diverse set of culturing media and additional substitutions known as passage adaptation can cause extra evolution in the target strain, leading to ineffective vaccines. Using 25,482 H3N2 HA1 sequences curated from Global Initiative on Sharing All Influenza Data and National Center for Biotechnology Information databases, we found that passage adaptation is a very dynamic process that changes over time and evolves in a seesaw like pattern. After crossing the species boundary from bird to human in 1968, the influenza H3N2 virus evolves to be better adapted to the human environment and passaging them in embryonated eggs (i.e., an avian environment) leads to increasingly stronger positive selection. On the contrary, passage adaptation to the mammalian cell lines changes from positive selection to negative selection. Using two statistical tests, we identified 19 codon positions around the receptor binding domain strongly contributing to passage adaptation in the embryonated egg. These sites show strong convergent evolution and overlap extensively with positively selected sites identified in humans, suggesting that passage adaptation can confound many of the earlier studies on influenza evolution. Interestingly, passage adaptation in recent years seems to target a few codon positions in antigenic surface epitopes, which makes it difficult to produce antigenically unaltered vaccines using embryonic eggs. Our study outlines another interesting scenario whereby both convergent and adaptive evolution are working in synchrony driving viral adaptation. Future studies from sequence analysis to vaccine production need to take careful consideration of passage adaptation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Fitness costs and benefits of novel herbicide tolerance in a noxious weed

    PubMed Central

    Baucom, Regina S.; Mauricio, Rodney

    2004-01-01

    Glyphosate, the active ingredient in the herbicide RoundUp, has increased dramatically in use over the past decade and constitutes a potent anthropogenic source of selection. In the southeastern United States, weedy morning glories have begun to develop tolerance to glyphosate, representing a unique opportunity to examine the evolutionary genetics of a novel trait. We found genetic variation for tolerance, indicating the potential for the population to respond to selection by glyphosate. However, the following significant evolutionary constraint exists: in the absence of glyphosate, tolerant genotypes produced fewer seeds than susceptible genotypes. The combination of strong positive directional selection in the presence of glyphosate and strong negative directional selection in its absence may indicate that the selective landscape of land use could drive the evolutionary trajectory of glyphosate tolerance. Understanding these evolutionary forces is imperative for devising comprehensive management strategies to help slow the rate of the evolution of tolerance. PMID:15326309

  15. Adaptive signals in algal Rubisco reveal a history of ancient atmospheric carbon dioxide.

    PubMed

    Young, J N; Rickaby, R E M; Kapralov, M V; Filatov, D A

    2012-02-19

    Rubisco, the most abundant enzyme on the Earth and responsible for all photosynthetic carbon fixation, is often thought of as a highly conserved and sluggish enzyme. Yet, different algal Rubiscos demonstrate a range of kinetic properties hinting at a history of evolution and adaptation. Here, we show that algal Rubisco has indeed evolved adaptively during ancient and distinct geological periods. Using DNA sequences of extant marine algae of the red and Chromista lineage, we define positive selection within the large subunit of Rubisco, encoded by rbcL, to occur basal to the radiation of modern marine groups. This signal of positive selection appears to be responding to changing intracellular concentrations of carbon dioxide (CO(2)) triggered by physiological adaptations to declining atmospheric CO(2). Within the ecologically important Haptophyta (including coccolithophores) and Bacillariophyta (diatoms), positive selection occurred consistently during periods of falling Phanerozoic CO(2) and suggests emergence of carbon-concentrating mechanisms. During the Proterozoic, a strong signal of positive selection after secondary endosymbiosis occurs at the origin of the Chromista lineage (approx. 1.1 Ga), with further positive selection events until 0.41 Ga, implying a significant and continuous decrease in atmospheric CO(2) encompassing the Cryogenian Snowball Earth events. We surmise that positive selection in Rubisco has been caused by declines in atmospheric CO(2) and hence acts as a proxy for ancient atmospheric CO(2).

  16. Adaptive signals in algal Rubisco reveal a history of ancient atmospheric carbon dioxide

    PubMed Central

    Young, J. N.; Rickaby, R. E. M.; Kapralov, M. V.; Filatov, D. A.

    2012-01-01

    Rubisco, the most abundant enzyme on the Earth and responsible for all photosynthetic carbon fixation, is often thought of as a highly conserved and sluggish enzyme. Yet, different algal Rubiscos demonstrate a range of kinetic properties hinting at a history of evolution and adaptation. Here, we show that algal Rubisco has indeed evolved adaptively during ancient and distinct geological periods. Using DNA sequences of extant marine algae of the red and Chromista lineage, we define positive selection within the large subunit of Rubisco, encoded by rbcL, to occur basal to the radiation of modern marine groups. This signal of positive selection appears to be responding to changing intracellular concentrations of carbon dioxide (CO2) triggered by physiological adaptations to declining atmospheric CO2. Within the ecologically important Haptophyta (including coccolithophores) and Bacillariophyta (diatoms), positive selection occurred consistently during periods of falling Phanerozoic CO2 and suggests emergence of carbon-concentrating mechanisms. During the Proterozoic, a strong signal of positive selection after secondary endosymbiosis occurs at the origin of the Chromista lineage (approx. 1.1 Ga), with further positive selection events until 0.41 Ga, implying a significant and continuous decrease in atmospheric CO2 encompassing the Cryogenian Snowball Earth events. We surmise that positive selection in Rubisco has been caused by declines in atmospheric CO2 and hence acts as a proxy for ancient atmospheric CO2. PMID:22232761

  17. Synthesis and SARs of novel lincomycin derivatives Part 5: optimization of lincomycin analogs exhibiting potent antibacterial activities by chemical modification at the 6- and 7-positions.

    PubMed

    Wakiyama, Yoshinari; Kumura, Ko; Umemura, Eijiro; Masaki, Satomi; Ueda, Kazutaka; Sato, Yasuo; Hirai, Yoko; Hayashi, Yoshio; Ajito, Keiichi

    2018-02-01

    In order to modify lincomycin at the C-6 and C-7 positions, we prepared target molecules, which have substituted pipecolinic acid at the 6-amino group and a para-substituted phenylthio group at the C-7 position, in application of palladium-catalyzed cross-coupling as a key reaction. As the result of structure-activity relationship (SAR) studies at the 6-position, analogs possessing 4'-cis-(cyclopropylmethyl)piperidine showed significantly strong antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with an erm gene. On the basis of SAR, we further synthesized novel analogs possessing 4'-cis-(cyclopropylmethyl)piperidine by transformation of a C-7 substituent. Consequently, novel derivatives possessing a para-heteroaromatic-phenylthio group at the C-7 position exhibited significantly strong activities against S. pneumoniae and S. pyogenes with an erm gene even when compared with those of telithromycin. Finally, in vivo efficacy of selected two derivatives was evaluated in a rat pulmonary infection model with resistant S. pneumoniae with erm + mef genes. One of them exhibited strong and constant in vivo efficacy in this model, and both compounds showed strong in vivo efficacy against resistant S. pneumoniae with a mef gene.

  18. Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction.

    PubMed

    Sunagar, Kartik; Johnson, Warren E; O'Brien, Stephen J; Vasconcelos, Vítor; Antunes, Agostinho

    2012-07-01

    Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among others, blockage of cyclic nucleotide-gated and voltage-gated ion channels and inhibition of smooth muscle contraction. We evaluated the molecular evolution of CRISPs in toxicoferan reptiles at both nucleotide and protein levels relative to their nonvenomous mammalian homologs. We show that the evolution of CRISP gene in these reptiles is significantly influenced by positive selection and in snakes (ω = 3.84) more than in lizards (ω = 2.33), whereas mammalian CRISPs were under strong negative selection (CRISP1 = 0.55, CRISP2 = 0.40, and CRISP3 = 0.68). The use of ancestral sequence reconstruction, mapping of mutations on the three-dimensional structure, and detailed evaluation of selection pressures suggests that the toxicoferan CRISPs underwent accelerated evolution aided by strong positive selection and directional mutagenesis, whereas their mammalian homologs are constrained by negative selection. Gene and protein-level selection analyses identified 41 positively selected sites in snakes and 14 sites in lizards. Most of these sites are located on the molecular surface (nearly 76% in snakes and 79% in lizards), whereas the backbone of the protein retains a highly conserved structural scaffold. Nearly 46% of the positively selected sites occur in the cysteine-rich domain of the protein. This directional mutagenesis, where the hotspots of mutations are found on the molecular surface and functional domains of the protein, acts as a diversifying mechanism for the exquisite biological targeting of CRISPs in toxicoferan reptiles. Finally, our analyses suggest that the evolution of toxicoferan-CRISP venoms might have been influenced by the specific predatory mechanism employed by the organism. CRISPs in Elapidae, which mostly employ neurotoxins, have experienced less positive selection pressure (ω = 2.86) compared with the "nonvenomous" colubrids (ω = 4.10) that rely on grip and constriction to capture the prey, and the Viperidae, a lineage that mostly employs haemotoxins (ω = 4.19). Relatively lower omega estimates in Anguimorph lizards (ω = 2.33) than snakes (ω = 3.84) suggests that lizards probably depend more on pace and powerful jaws for predation than venom.

  19. Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria

    PubMed Central

    Ramiro, Ricardo S.; Barroso-Batista, João; Güleresi, Daniela; Lourenço, Marta; Gordo, Isabel

    2017-01-01

    Abstract The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut. PMID:28961745

  20. Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection

    PubMed Central

    Xue, Yali ; Daly, Allan ; Yngvadottir, Bryndis ; Liu, Mengning ; Coop, Graham ; Kim, Yuseob ; Sabeti, Pardis ; Chen, Yuan ; Stalker, Jim ; Huckle, Elizabeth ; Burton, John ; Leonard, Steven ; Rogers, Jane ; Tyler-Smith, Chris 

    2006-01-01

    The human caspase-12 gene is polymorphic for the presence or absence of a stop codon, which results in the occurrence of both active (ancestral) and inactive (derived) forms of the gene in the population. It has been shown elsewhere that carriers of the inactive gene are more resistant to severe sepsis. We have now investigated whether the inactive form has spread because of neutral drift or positive selection. We determined its distribution in a worldwide sample of 52 populations and resequenced the gene in 77 individuals from the HapMap Yoruba, Han Chinese, and European populations. There is strong evidence of positive selection from low diversity, skewed allele-frequency spectra, and the predominance of a single haplotype. We suggest that the inactive form of the gene arose in Africa ∼100–500 thousand years ago (KYA) and was initially neutral or almost neutral but that positive selection beginning ∼60–100 KYA drove it to near fixation. We further propose that its selective advantage was sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased. PMID:16532395

  1. Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

    PubMed Central

    Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

    2013-01-01

    Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

  2. Phycoerythrin evolution and diversification of spectral phenotype in marine Synechococcus and related picocyanobacteria.

    PubMed

    Everroad, R Craig; Wood, A Michelle

    2012-09-01

    In marine Synechococcus there is evidence for the adaptive evolution of spectrally distinct forms of the major light harvesting pigment phycoerythrin (PE). Recent research has suggested that these spectral forms of PE have a different evolutionary history than the core genome. However, a lack of explicit statistical testing of alternative hypotheses or for selection on these genes has made it difficult to evaluate the evolutionary relationships between spectral forms of PE or the role horizontal gene transfer (HGT) may have had in the adaptive phenotypic evolution of the pigment system in marine Synechococcus. In this work, PE phylogenies of picocyanobacteria with known spectral phenotypes, including newly co-isolated strains of marine Synechococcus from the Gulf of Mexico, were constructed to explore the diversification of spectral phenotype and PE evolution in this group more completely. For the first time, statistical evaluation of competing evolutionary hypotheses and tests for positive selection on the PE locus in picocyanobacteria were performed. Genes for PEs associated with specific PE spectral phenotypes formed strongly supported monophyletic clades within the PE tree with positive directional selection driving evolution towards higher phycourobilin (PUB) content. The presence of the PUB-lacking phenotype in PE-containing marine picocyanobacteria from cyanobacterial lineages identified as Cyanobium is best explained by HGT into this group from marine Synechococcus. Taken together, these data provide strong examples of adaptive evolution of a single phenotypic trait in bacteria via mutation, positive directional selection and horizontal gene transfer. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Widespread Positive Selection Drives Differentiation of Centromeric Proteins in the Drosophila melanogaster subgroup.

    PubMed

    Beck, Emily A; Llopart, Ana

    2015-11-25

    Rapid evolution of centromeric satellite repeats is thought to cause compensatory amino acid evolution in interacting centromere-associated kinetochore proteins. Cid, a protein that mediates kinetochore/centromere interactions, displays particularly high amino acid turnover. Rapid evolution of both Cid and centromeric satellite repeats led us to hypothesize that the apparent compensatory evolution may extend to interacting partners in the Condensin I complex (i.e., SMC2, SMC4, Cap-H, Cap-D2, and Cap-G) and HP1s. Missense mutations in these proteins often result in improper centromere formation and aberrant chromosome segregation, thus selection for maintained function and coevolution among proteins of the complex is likely strong. Here, we report evidence of rapid evolution and recurrent positive selection in seven centromere-associated proteins in species of the Drosophila melanogaster subgroup, and further postulate that positive selection on these proteins could be a result of centromere drive and compensatory changes, with kinetochore proteins competing for optimal spindle attachment.

  4. Active season microhabitat and vegetation selection by giant gartersnakes associated with a restored marsh in California

    USGS Publications Warehouse

    Halstead, Brian J.; Valcarcel, Patricia; Wylie, Glenn D.; Coates, Peter S.; Casazza, Michael L.; Rosenberg, Daniel K.

    2016-01-01

    Studies of habitat selection can reveal important patterns to guide habitat restoration and management for species of conservation concern. Giant gartersnakes Thamnophis gigas are endemic to the Central Valley of California, where >90% of their historical wetland habitat has been converted to agricultural and other uses. Information about the selection of habitats by individual giant gartersnakes would guide habitat restoration by indicating which habitat features and vegetation types are likely to be selected by these rare snakes. We examined activity patterns and selection of microhabitats and vegetation types by adult female giant gartersnakes with radiotelemetry at a site composed of rice agriculture and restored wetlands using a paired case-control study design. Adult female giant gartersnakes were 14.7 (95% credible interval [CRI] = 9.4–23.7) times more likely to be active (foraging, mating, or moving) when located in aquatic habitats than when located in terrestrial habitats. Microhabitats associated with cover—particularly emergent vegetation, terrestrial vegetation, and litter—were positively selected by giant gartersnakes. Individual giant gartersnakes varied greatly in their selection of rice and rock habitats, but varied little in their selection of open water. Tules Schoenoplectus acutus were the most strongly selected vegetation type, and duckweed Lemna spp., water-primrose Ludwigia spp., forbs, and grasses also were positively selected at the levels of availability observed at our study site. Management practices that promote the interface of water with emergent aquatic and herbaceous terrestrial vegetation will likely benefit giant gartersnakes. Given their strong selection of tules, restoration of native tule marshes will likely provide the greatest benefit to these threatened aquatic snakes.

  5. Genome-wide detection and characterization of positive selection in human populations.

    PubMed

    Sabeti, Pardis C; Varilly, Patrick; Fry, Ben; Lohmueller, Jason; Hostetter, Elizabeth; Cotsapas, Chris; Xie, Xiaohui; Byrne, Elizabeth H; McCarroll, Steven A; Gaudet, Rachelle; Schaffner, Stephen F; Lander, Eric S; Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Johnson, Todd A; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

    2007-10-18

    With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

  6. A screen for immunity genes evolving under positive selection in Drosophila.

    PubMed

    Jiggins, F M; Kim, K W

    2007-05-01

    Genes involved in the immune system tend to have higher rates of adaptive evolution than other genes in the genome, probably because they are coevolving with pathogens. We have screened a sample of Drosophila genes to identify those evolving under positive selection. First, we identified rapidly evolving immunity genes by comparing 140 loci in Drosophila erecta and D. yakuba. Secondly, we resequenced 23 of the fastest evolving genes from the independent species pair D. melanogaster and D. simulans, and identified those under positive selection using a McDonald-Kreitman test. There was strong evidence of adaptive evolution in two serine proteases (persephone and spirit) and a homolog of the Anopheles serpin SRPN6, and weaker evidence in another serine protease and the death domain protein dFADD. These results add to mounting evidence that immune signalling pathway molecules often evolve rapidly, possibly because they are sites of host-parasite coevolution.

  7. Independent priming of location and color in identification of briefly presented letters.

    PubMed

    Ásgeirsson, Árni Gunnar; Kristjánsson, Árni; Bundesen, Claus

    2014-01-01

    Attention shifts are facilitated if the items to be attended remain the same across trials. Some researchers argue that this priming effect is perceptual, whereas others propose that priming is postperceptual, involving facilitated response selection. The experimental findings have not been consistent regarding the roles of variables such as task difficulty, response repetition, expectancies, and decision-making. Position priming, when repetition of a target position facilitates responses on a subsequent trial, is another source of disagreement among researchers. Experimental results have likewise been inconsistent as to whether position priming is dependent on the repetition of target features or has an independent effect on attention shifts. We attempted to isolate the perceptual components of priming by presenting brief (10-180 ms) search arrays to eight healthy observers. The task was to identify a color-singleton letter among distractors. All stimulus presentation contingencies were randomized, and responses were unspeeded, to avoid effects of observer expectation and postperceptual effects. Repeating target color and/or position strongly improved performance. The effects of color and position repetition were independent of one another and were stable across participants. The results argue for a strong perceptual component in priming, which biases selection toward recent target features and positions, showing that perceptual mechanisms are sufficient to produce priming in visual search and that such effects can be elicited with limited sensory evidence. The results are the first to demonstrate independent priming of color and position in the identification of briefly presented, postmasked stimuli.

  8. Modeling HIV-1 Drug Resistance as Episodic Directional Selection

    PubMed Central

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L.; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. PMID:22589711

  9. Modeling HIV-1 drug resistance as episodic directional selection.

    PubMed

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  10. The complexity of selection at the major primate β-defensin locus

    PubMed Central

    Semple, Colin AM; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

    2005-01-01

    Background We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. Results We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Conclusions Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design. PMID:15904491

  11. Strong signatures of selection in the domestic pig genome.

    PubMed

    Rubin, Carl-Johan; Megens, Hendrik-Jan; Martinez Barrio, Alvaro; Maqbool, Khurram; Sayyab, Shumaila; Schwochow, Doreen; Wang, Chao; Carlborg, Örjan; Jern, Patric; Jørgensen, Claus B; Archibald, Alan L; Fredholm, Merete; Groenen, Martien A M; Andersson, Leif

    2012-11-27

    Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig--the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.

  12. Strong signatures of selection in the domestic pig genome

    PubMed Central

    Rubin, Carl-Johan; Megens, Hendrik-Jan; Barrio, Alvaro Martinez; Maqbool, Khurram; Sayyab, Shumaila; Schwochow, Doreen; Wang, Chao; Carlborg, Örjan; Jern, Patric; Jørgensen, Claus B.; Archibald, Alan L.; Fredholm, Merete; Groenen, Martien A. M.; Andersson, Leif

    2012-01-01

    Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig—the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection. PMID:23151514

  13. Usefulness of a break-apart FISH assay in the diagnosis of Xp11.2 translocation renal cell carcinoma.

    PubMed

    Kim, Soo Hee; Choi, Yoomi; Jeong, Hae Yeon; Lee, Kyoungbun; Chae, Ji Youn; Moon, Kyung Chul

    2011-09-01

    Xp11.2 translocation renal cell carcinoma (RCC) is a rare subtype of RCC predominantly reported in young patients. It results from gene fusions between the transcription factor E3 (TFE3) gene, which is located on chromosome Xp11.2, and various fusion partners. Recently, a dual color, break-apart fluorescence in situ hybridization (FISH) assay to detect Xp11.2 translocation was reported. We performed this study to evaluate the usefulness of the FISH assay in the diagnosis of Xp11.2 translocation RCC using a commercially available TFE3 break-apart probe. We immunohistochemically analyzed TFE3 nuclear expression in 809 cases of RCCs using 14 tissue microarray blocks and selected nine cases those showed moderate to strong positive nuclear immunoreactivity for TFE3. The extent of TFE3 nuclear expression was variable. The TFE3 FISH assay was performed in these 9 selected cases and 44 negative control cases. Only four out of nine selected cases showed the TFE3 break-apart signal. TFE3 FISH-positive cases mainly showed diffuse and strong TFE3 immunopositivity, but one case revealed focal and moderate TFE3 staining. On the contrary, TFE3 FISH-negative cases mainly revealed focal and moderate TFE3 immunoreactivity, however, one FISH-negative case revealed diffuse and strong TFE3 nuclear immunopositivity. All negative control cases revealed normal TFE3 FISH results. Our results reveal that TFE3 immunohistochemistry can show false-positive results, and that the TFE3 break-apart FISH assay is a useful complementary method for confirming the diagnosis of Xp11.2 translocation RCC.

  14. Diet and prey selection by Lake Superior lake trout during springs 1986-2001

    USGS Publications Warehouse

    Ray, B.A.; Hrabik, T.R.; Ebener, M.P.; Gorman, O.T.; Schreiner, D.R.; Schram, S.T.; Sitar, S.P.; Mattes, W.P.; Bronte, C.R.

    2007-01-01

    We describe the diet and prey selectivity of lean (Salvelinus namaycush namaycush) and siscowet lake trout (S. n. siscowet) collected during spring (April–June) from Lake Superior during 1986–2001. We estimated prey selectivity by comparing prey numerical abundance estimates from spring bottom trawl surveys and lake trout diet information in similar areas from spring gill net surveys conducted annually in Lake Superior. Rainbow smelt (Osmerus mordax) was the most common prey and was positively selected by both lean and siscowet lake trout throughout the study. Selection by lean lake trout for coregonine (Coregonus spp.) prey increased after 1991 and corresponded with a slight decrease in selection for rainbow smelt. Siscowet positively selected for rainbow smelt after 1998, a change that was coincident with the decrease in selection for this prey item by lean lake trout. However, diet overlap between lean and siscowet lake trout was not strong and did not change significantly over the study period. Rainbow smelt remains an important prey species for lake trout in Lake Superior despite declines in abundance.

  15. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    PubMed

    Botosso, Viviane F; Zanotto, Paolo M de A; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E; Vieira, Sandra E; Stewien, Klaus E; Peret, Teresa C T; Jamal, Leda F; Pardini, Maria I de M C; Pinho, João R R; Massad, Eduardo; Sant'anna, Osvaldo A; Holmes, Eddie C; Durigon, Edison L

    2009-01-01

    Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  16. Content Characteristics Driving the Diffusion of Antismoking Messages: Implications for Cancer Prevention in the Emerging Public Communication Environment

    PubMed Central

    2013-01-01

    This study examined how content characteristics of antitobacco messages affect smokers’ selective exposure to and social sharing of those messages. Results from an experiment revealed that content features predicting smokers’ selection of antismoking messages are different from those predicting whether those messages are shared. Antismoking messages smokers tend to select are characterized by strong arguments (odds ratio = 2.02, P = .02) and positive sentiments (odds ratio = 3.08, P = .03). Once selected, the messages more likely to be retransmitted by smokers were those with novel arguments (B = .83, P = .002) and positive sentiments (B = 1.65, P = .005). This research adds to the literature about the content characteristics driving the social diffusion of antitobacco messages and contributes to our understanding of the role of persuasive messages about smoking cessation in the emerging public communication environment. PMID:24395989

  17. Evolution of genetic architecture under directional selection.

    PubMed

    Hansen, Thomas F; Alvarez-Castro, José M; Carter, Ashley J R; Hermisson, Joachim; Wagner, Günter P

    2006-08-01

    We investigate the multilinear epistatic model under mutation-limited directional selection. We confirm previous results that only directional epistasis, in which genes on average reinforce or diminish each other's effects, contribute to the initial evolution of mutational effects. Thus, either canalization or decanalization can occur under directional selection, depending on whether positive or negative epistasis is prevalent. We then focus on the evolution of the epistatic coefficients themselves. In the absence of higher-order epistasis, positive pairwise epistasis will tend to weaken relative to additive effects, while negative pairwise epistasis will tend to become strengthened. Positive third-order epistasis will counteract these effects, while negative third-order epistasis will reinforce them. More generally, gene interactions of all orders have an inherent tendency for negative changes under directional selection, which can only be modified by higher-order directional epistasis. We identify three types of nonadditive quasi-equilibrium architectures that, although not strictly stable, can be maintained for an extended time: (1) nondirectional epistatic architectures; (2) canalized architectures with strong epistasis; and (3) near-additive architectures in which additive effects keep increasing relative to epistasis.

  18. Population genetics of mouse lemur vomeronasal receptors: current versus past selection and demographic inference.

    PubMed

    Hohenbrink, Philipp; Mundy, Nicholas I; Radespiel, Ute

    2017-01-21

    A major effort is underway to use population genetic approaches to identify loci involved in adaptation. One issue that has so far received limited attention is whether loci that show a phylogenetic signal of positive selection in the past also show evidence of ongoing positive selection at the population level. We address this issue using vomeronasal receptors (VRs), a diverse gene family in mammals involved in intraspecific communication and predator detection. In mouse lemurs, we previously demonstrated that both subfamilies of VRs (V1Rs and V2Rs) show a strong signal of directional selection in interspecific analyses. We predicted that ongoing sexual selection and/or co-evolution with predators may lead to current directional or balancing selection on VRs. Here, we re-sequence 17 VRs and perform a suite of selection and demographic analyses in sympatric populations of two species of mouse lemurs (Microcebus murinus and M. ravelobensis) in northwestern Madagascar. M. ravelobensis had consistently higher genetic diversity at VRs than M. murinus. In general, we find little evidence for positive selection, with most loci evolving under purifying selection and one locus even showing evidence of functional loss in M. ravelobensis. However, a few loci in M. ravelobensis show potential evidence of positive selection. Using mismatch distributions and expansion models, we infer a more recent colonisation of the habitat by M. murinus than by M. ravelobensis, which most likely speciated in this region earlier on. These findings suggest that the analysis of VR variation is useful in inferring demographic and phylogeographic history of mouse lemurs. In conclusion, this study reveals a substantial heterogeneity over time in selection on VR loci, suggesting that VR evolution is episodic.

  19. Gender Scripts in Professional Writing Textbooks.

    ERIC Educational Resources Information Center

    Carrell, David

    1991-01-01

    Examines sexual stereotypes in selected professional writing textbooks published from the 1930s to the 1950s. Maintains that these textbooks--portraying women as subservient, emotional, and frivolous, and men as decisive, logical, and strong--suggest that men are more suited for positions of authority, and have played an important role in…

  20. Item Selection, Evaluation, and Simple Structure in Personality Data

    PubMed Central

    Pettersson, Erik; Turkheimer, Eric

    2010-01-01

    We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

  1. Selective mode of action of guanidine-containing non-peptides at human NPFF receptors.

    PubMed

    Findeisen, Maria; Würker, Cäcilia; Rathmann, Daniel; Meier, René; Meiler, Jens; Olsson, Roger; Beck-Sickinger, Annette G

    2012-07-12

    The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By use of four nonpeptidic compounds and the peptide mimetics RF9 and BIBP3226, agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated. The binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of AC-216 interacts with position 7.35 in the NPFF(1) but not in the NPFF(2) receptor. These results provide distinct insights into the receptor specific binding pockets, which is necessary for the development of drugs to address the NPFF system.

  2. Selective mode of action of guanidine-containing non-peptides at human NPFF receptors

    PubMed Central

    Findeisen, Maria; Würker, Cäcilia; Rathmann, Daniel; Meier, René; Meiler, Jens; Olsson, Roger; Beck-Sickinger, Annette G.

    2012-01-01

    The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By using four non-peptidic compounds and the peptide mimetics RF9 and BIBP3226 agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated, the binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII, and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of AC-216 interacts with position 7.35 in the NPFF1 but not in the NPFF2 receptor. These results provide distinct insights into the receptor specific binding pockets, which is necessary for the development of drugs to address the NPFF system. PMID:22708927

  3. Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

    PubMed

    Zhang, Xuqing; Li, Xiaojie; Allan, George F; Sbriscia, Tifanie; Linton, Olivia; Lundeen, Scott G; Sui, Zhihua

    2007-08-09

    A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

  4. Positive affect, meaning in life, and future time perspective: an application of socioemotional selectivity theory.

    PubMed

    Hicks, Joshua A; Trent, Jason; Davis, William E; King, Laura A

    2012-03-01

    Four studies tested the prediction that positive affect (PA) would relate more strongly to meaning in life (MIL) as a function of perceived time limitations. In Study 1 (N = 360), adults completed measures of PA and MIL. As predicted, PA related more strongly to MIL for older, compared to younger, participants. In Studies 2 and 3, adults (N = 514) indicated their current position in their life span, and rated their MIL. PA, whether naturally occurring (Study 2) or induced (Study 3), was a stronger predictor of MIL for individuals who perceived themselves as having a limited amount of time left to live. Finally, in Study 4 (N = 98) students completed a measure of PA, MIL, and future time perspective (FTP). Results showed that PA was more strongly linked to MIL for those who believed they had fewer opportunities left to pursue their goals. Overall, these findings suggest that the experience of PA becomes increasingly associated with the experience of MIL as the perception of future time becomes limited. The contribution of age related processes to judgments of well-being are discussed.

  5. Strength and Power Qualities Are Highly Associated With Punching Impact in Elite Amateur Boxers.

    PubMed

    Loturco, Irineu; Nakamura, Fabio Y; Artioli, Guilherme G; Kobal, Ronaldo; Kitamura, Katia; Cal Abad, Cesar C; Cruz, Igor F; Romano, Felipe; Pereira, Lucas A; Franchini, Emerson

    2016-01-01

    This study investigated the relationship between punching impact and selected strength and power variables in 15 amateur boxers from the Brazilian National Team (9 men and 6 women). Punching impact was assessed in the following conditions: 3 jabs starting from the standardized position, 3 crosses starting from the standardized position, 3 jabs starting from a self-selected position, and 3 crosses starting from a self-selected position. For punching tests, a force platform (1.02 × 0.76 m) covered by a body shield was mounted on the wall at a height of 1 m, perpendicular to the floor. The selected strength and power variables were vertical jump height (in squat jump and countermovement jump), mean propulsive power in the jump squat, bench press (BP), and bench throw, maximum isometric force in squat and BP, and rate of force development in the squat and BP. Sex and position main effects were observed, with higher impact for males compared with females (p ≤ 0.05) and the self-selected distance resulting in higher impact in the jab technique compared with the fixed distance (p ≤ 0.05). Finally, the correlations between strength/power variables and punching impact indices ranged between 0.67 and 0.85. Because of the strong associations between punching impact and strength/power variables (e.g., lower limb muscle power), this study provides important information for coaches to specifically design better training strategies to improve punching impact.

  6. Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

    PubMed

    Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2016-09-11

    A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

    PubMed Central

    Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

  8. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    PubMed

    Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  9. Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

    PubMed

    Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

    2016-03-01

    A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. How nonuniform contact profiles of T cell receptors modulate thymic selection outcomes

    NASA Astrophysics Data System (ADS)

    Chen, Hanrong; Chakraborty, Arup K.; Kardar, Mehran

    2018-03-01

    T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies. Past theoretical work cast thymic selection as an extreme value problem and characterized the statistical enrichment or depletion of amino acids in the postselection TCR repertoire, showing how T cells are selected to be able to specifically recognize peptides derived from diverse pathogens yet have limited self-reactivity. Here, we investigate how the diversity of the postselection TCR repertoire is modified when TCRs make nonuniform contacts with peptide-MHC. Specifically, we were motivated by recent experiments showing that amino acids at certain positions of a TCR sequence have large effects on thymic selection outcomes, and crystal structure data that reveal a nonuniform contact profile between a TCR and its peptide-MHC ligand. Using a representative TCR contact profile as an illustration, we show via simulations that the statistical enrichment or depletion of amino acids now varies by position according to the contact profile, and, importantly, it depends on the implementation of nonuniform contacts during thymic selection. We explain these nontrivial results analytically. Our study has implications for understanding the selection forces that shape the functionality of the postselection TCR repertoire.

  11. Alteration of the C-terminal ligand specificity of the erbin PDZ domain by allosteric mutational effects.

    PubMed

    Murciano-Calles, Javier; McLaughlin, Megan E; Erijman, Ariel; Hooda, Yogesh; Chakravorty, Nishant; Martinez, Jose C; Shifman, Julia M; Sidhu, Sachdev S

    2014-10-23

    Modulation of protein binding specificity is important for basic biology and for applied science. Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus. Our goal was to engineer variants of the Erbin PDZ domain with altered specificity for the most C-terminal position (position 0) where a Val is strongly preferred by the wild-type domain. We constructed a library of PDZ domains by randomizing residues in direct contact with position 0 and in a loop that is close to but does not contact position 0. We used phage display to select for PDZ variants that bind to 19 peptide ligands differing only at position 0. To verify that each obtained PDZ domain exhibited the correct binding specificity, we selected peptide ligands for each domain. Despite intensive efforts, we were only able to evolve Erbin PDZ domain variants with selectivity for the aliphatic C-terminal side chains Val, Ile and Leu. Interestingly, many PDZ domains with these three distinct specificities contained identical amino acids at positions that directly contact position 0 but differed in the loop that does not contact position 0. Computational modeling of the selected PDZ domains shows how slight conformational changes in the loop region propagate to the binding site and result in different binding specificities. Our results demonstrate that second-sphere residues could be crucial in determining protein binding specificity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Antibacterial activities of fluorescent nano assembled triphenylamine phosphonium ionic liquids.

    PubMed

    Brunel, Frédéric; Lautard, Christelle; Garzino, Frédéric; Giorgio, Suzanne; Raimundo, Jean M; Bolla, Jean M; Camplo, Michel

    2016-08-01

    Staphylococcus aureus, a Gram positive coccal bacterium is a major cause of nosocomial infection. We report the synthesis of new triphenylamine phosphonium ionic liquids which are able to self-assemble into multiwall nanoassemblies and to reveal a strong bactericidal activity (MIC=0.5mg/L) for Gram positive bacteria (including resistant strains) comparable to that of standard antibiotics. Time kill, metabolism and fluorescence confocal microscopy studies show a quasi-instantaneously penetration of the nanoassemblies inside the bacteria resulting of a rapid blocking (30min) of their proliferation. As confirmed by rezasurin reduction monitoring, these compounds strongly affect the bacterial metabolism and a Gram positive versus Gram negative selectivity is clearly observed. These fluorescent phosphonium ionic liquid might constitute a useful tool for both translocation studies and to tackle infectious diseases related to the field of implantology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.

    PubMed

    Zapata, Luis; Pich, Oriol; Serrano, Luis; Kondrashov, Fyodor A; Ossowski, Stephan; Schaefer, Martin H

    2018-05-31

    Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes. In summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments.

  14. Continental-scale footprint of balancing and positive selection in a small rodent (Microtus arvalis).

    PubMed

    Fischer, Martin C; Foll, Matthieu; Heckel, Gerald; Excoffier, Laurent

    2014-01-01

    Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis) presenting high levels of differentiation between populations (average F ST = 0.31). We studied 3,839 Amplified Fragment Length Polymorphism (AFLP) markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138) being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic diversity of the common vole, which is more influenced by positive selection and neutral processes like drift and demographic history.

  15. Diversity of cuticular wax among Salix species and Populus species hybrids.

    PubMed

    Cameron, Kimberly D; Teece, Mark A; Bevilacqua, Eddie; Smart, Lawrence B

    2002-08-01

    The leaf cuticular waxes of three Salix species and two Populus species hybrids, selected for their ability to produce high amounts of biomass, were characterized. Samples were extracted in CH(2)Cl(2) three times over the growing season. Low kV SEM was utilized to observe differences in the ultrastructure of leaf surfaces from each clone. Homologous series of wax components were classified into organic groups, and the variation in wax components due to clone, sample time, and their interaction was identified. All Salix species and Populus species hybrids showed differences in total wax load at each sampling period, whereas the pattern of wax deposition over time differed only between the Salix species. A strong positive relationship was identified between the entire homologous series of alcohols and total wax load in all clones. Similarly strong relationships were observed between fatty acids and total wax load as well as fatty acids and alcohols in two Salix species and one Populus species hybrid. One Salix species, S. dasyclados, also displayed a strong positive relationship between alcohols and alkanes. These data indicate that species grown under the same environmental conditions produce measurably different cuticular waxes and that regulation of wax production appears to be different in each species. The important roles cuticular waxes play in drought tolerance, pest, and pathogen resistance, as well as the ease of wax extraction and analysis, strongly suggest that the characteristics of the cuticular wax may prove to be useful selectable traits in a breeding program.

  16. Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.

    PubMed

    Stamenić, Tamara Timić; Poe, Michael M; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M; Savić, Miroslav M

    2016-11-15

    We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABA A receptors containing the α5 subunit (α5GABA A Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABA A receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200mg/kg), but at the price of activating non-α5 GABA A Rs as well as the desired α5GABA A Rs at the highest dose. At the dose of 10mg/kg, which elicits a strong positive modulation of α5GABA A Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABA A Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit

    PubMed Central

    Stamenić, Tamara Timić; Poe, Michael M.; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M.; Savić, Miroslav M.

    2016-01-01

    We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABAA receptors containing the α5 subunit (α5GABAARs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABAA receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2′F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-α5 GABAARs as well as the desired α5GABAARs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of α5GABAARs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABAARs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. PMID:27639297

  18. Expression level, cellular compartment and metabolic network position all influence the average selective constraint on mammalian enzymes

    PubMed Central

    2011-01-01

    Background A gene's position in regulatory, protein interaction or metabolic networks can be predictive of the strength of purifying selection acting on it, but these relationships are neither universal nor invariably strong. Following work in bacteria, fungi and invertebrate animals, we explore the relationship between selective constraint and metabolic function in mammals. Results We measure the association between selective constraint, estimated by the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions, and several, primarily metabolic, measures of gene function. We find significant differences between the selective constraints acting on enzyme-coding genes from different cellular compartments, with the nucleus showing higher constraint than genes from either the cytoplasm or the mitochondria. Among metabolic genes, the centrality of an enzyme in the metabolic network is significantly correlated with Ka/Ks. In contrast to yeasts, gene expression magnitude does not appear to be the primary predictor of selective constraint in these organisms. Conclusions Our results imply that the relationship between selective constraint and enzyme centrality is complex: the strength of selective constraint acting on mammalian genes is quite variable and does not appear to exclusively follow patterns seen in other organisms. PMID:21470417

  19. Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

    PubMed Central

    Botosso, Viviane F.; Zanotto, Paolo M. de A.; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E.; Vieira, Sandra E.; Stewien, Klaus E.; Peret, Teresa C. T.; Jamal, Leda F.; Pardini, Maria I. de M. C.; Pinho, João R. R.; Massad, Eduardo; Sant'Anna, Osvaldo A.; Holmes, Eddie C.; Durigon, Edison L.

    2009-01-01

    Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites. PMID:19119418

  20. Rapid evolution of PARP genes suggests a broad role for ADP-ribosylation in host-virus conflicts.

    PubMed

    Daugherty, Matthew D; Young, Janet M; Kerns, Julie A; Malik, Harmit S

    2014-01-01

    Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic 'arms races' with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in 'housekeeping' functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.

  1. Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts

    PubMed Central

    Daugherty, Matthew D.; Young, Janet M.; Kerns, Julie A.; Malik, Harmit S.

    2014-01-01

    Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts. PMID:24875882

  2. Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls

    PubMed Central

    Booiman, Thijs; Wit, Ferdinand W.; Girigorie, Arginell F.; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Franceschi, Claudio; Deeks, Steven G.; Winston, Alan; Reiss, Peter

    2017-01-01

    HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank. Despite long-term ART (median of 12.2 years), HIV-infected adults had lower CD4+ T-cell counts and higher CD8+ T-cell counts compared to well-matched HIV-negative COBRA participants. The proportion of CD38+HLA-DR+ and PD-1+ CD4+ T-cells was higher in HIV-positive cohort compared to the two HIV-negative cohorts. The proportion CD57+ and CD27−CD28− cells of both CD4+ and CD8+ T-cells in HIV-positives was higher compared to unselected adults (blood bank) as reported before but this difference was not apparent in comparison with well-matched HIV-negative COBRA participants. Multiple regression analysis showed that the presence of an increased proportion of terminally differentiated T cells was strongly associated with CMV infection. Compared to appropriately selected HIV-negative controls, HIV-positive individuals on ART with long-term suppressed viraemia exhibited incomplete immune recovery and increased immune activation/exhaustion. CMV infection rather than treated HIV infection appears to have more consistent effects on measures of terminal differentiation of T cells. PMID:28806406

  3. Biological function in the twilight zone of sequence conservation.

    PubMed

    Ponting, Chris P

    2017-08-16

    Strong DNA conservation among divergent species is an indicator of enduring functionality. With weaker sequence conservation we enter a vast 'twilight zone' in which sequence subject to transient or lower constraint cannot be distinguished easily from neutrally evolving, non-functional sequence. Twilight zone functional sequence is illuminated instead by principles of selective constraint and positive selection using genomic data acquired from within a species' population. Application of these principles reveals that despite being biochemically active, most twilight zone sequence is not functional.

  4. STRONG POSITIVE SELECTION AND HABITAT SPECIFIC AMINO ACID SUBSTITUTION PATTERNS IN A MHC FROM AN ESTUARINE FISH UNDER INTENSE POLLUTION STRESS

    EPA Science Inventory

    Population-level studies using the major histocompatibility complex (Mhc) have linked specific alleles with specific diseases, but data requirements are high and power to detect disease association is low. A novel use of Mhc population surveys is that they map allelic substituti...

  5. Cultivating Imaginative Thinking: Teacher Strategies Used in High-Performing Arts Education Classrooms

    ERIC Educational Resources Information Center

    Fleming, Josephine; Gibson, Robyn; Anderson, Michael; Martin, Andrew J.; Sudmalis, David

    2016-01-01

    This article reports on recent case-study research that examined teacher- and student-level processes in nine Australian arts classrooms. The selected classrooms, based on the results of a connected longitudinal study, demonstrated strong positive links between arts participation and academic motivation, engagement and achievement. The focus here…

  6. Positive Selection during the Evolution of the Blood Coagulation Factors in the Context of Their Disease-Causing Mutations

    PubMed Central

    Rallapalli, Pavithra M.; Orengo, Christine A.; Studer, Romain A.; Perkins, Stephen J.

    2014-01-01

    Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII–FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other. It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations. In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing. A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this. This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy. PMID:25158795

  7. Sexual selection and the adaptive evolution of PKDREJ protein in primates and rodents

    PubMed Central

    Vicens, Alberto; Gómez Montoto, Laura; Couso-Ferrer, Francisco; Sutton, Keith A.; Roldan, Eduardo R.S.

    2015-01-01

    PKDREJ is a testis-specific protein thought to be located on the sperm surface. Functional studies in the mouse revealed that loss of PKDREJ has effects on sperm transport and the ability to undergo an induced acrosome reaction. Thus, PKDREJ has been considered a potential target of post-copulatory sexual selection in the form of sperm competition. Proteins involved in reproductive processes often show accelerated evolution. In many cases, this rapid divergence is promoted by positive selection which may be driven, at least in part, by post-copulatory sexual selection. We analysed the evolution of the PKDREJ protein in primates and rodents and assessed whether PKDREJ divergence is associated with testes mass relative to body mass, which is a reliable proxy of sperm competition levels. Evidence of an association between the evolutionary rate of the PKDREJ gene and testes mass relative to body mass was not found in primates. Among rodents, evidence of positive selection was detected in the Pkdrej gene in the family Cricetidae but not in Muridae. We then assessed whether Pkdrej divergence is associated with episodes of sperm competition in these families. We detected a positive significant correlation between the evolutionary rates of Pkdrej and testes mass relative to body mass in cricetids. These findings constitute the first evidence of post-copulatory sexual selection influencing the evolution of a protein that participates in the mechanisms regulating sperm transport and the acrosome reaction, strongly suggesting that positive selection may act on these fertilization steps, leading to advantages in situations of sperm competition. PMID:25304980

  8. Positive interventions: An emotion regulation perspective.

    PubMed

    Quoidbach, Jordi; Mikolajczak, Moïra; Gross, James J

    2015-05-01

    The rapid growth of the literature on positive interventions to increase "happiness" has suggested the need for an overarching conceptual framework to integrate the many and apparently disparate findings. In this review, we used the process model of emotion regulation (Gross, 1998) to organize the existing literature on positive interventions and to advance theory by clarifying the mechanisms underlying their effectiveness. We have proposed that positive emotions can be increased both in the short- and longer-term through 5 families of emotion regulation strategies (i.e., situation selection, situation modification, attentional deployment, cognitive change, and response modulation), showing how these emotion regulation strategies can be applied before, during, and after positive emotional events. Regarding short-term increases in positive emotions, our review found that attentional deployment, cognitive change, and response modulation strategies have received the most empirical support, whereas more work is needed to establish the effectiveness of situation selection and situation modification strategies. Regarding longer-term increases in positive emotions, strategies such as situation selection during an event and attentional deployment before, during, and after an event have received strong empirical support and are at the center of many positive interventions. However, more work is needed to establish the specific benefits of the other strategies, especially situation modification. We argue that our emotion regulation framework clarifies existing interventions and points the way for new interventions that might be used to increase positive emotions in both nonclinical and clinical populations. (c) 2015 APA, all rights reserved).

  9. Longitudinal analyses of correlated response efficiencies of fillet traits in Nile tilapia.

    PubMed

    Turra, E M; Fernandes, A F A; de Alvarenga, E R; Teixeira, E A; Alves, G F O; Manduca, L G; Murphy, T W; Silva, M A

    2018-03-01

    Recent studies with Nile tilapia have shown divergent results regarding the possibility of selecting on morphometric measurements to promote indirect genetic gains in fillet yield (FY). The use of indirect selection for fillet traits is important as these traits are only measurable after harvesting. Random regression models are a powerful tool in association studies to identify the best time point to measure and select animals. Random regression models can also be applied in a multiple trait approach to analyze indirect response to selection, which would avoid the need to sacrifice candidate fish. Therefore, the aim of this study was to investigate the genetic relationships between several body measurements, weight and fillet traits throughout the growth period and to evaluate the possibility of indirect selection for fillet traits in Nile tilapia. Data were collected from 2042 fish and was divided into two subsets. The first subset was used to estimate genetic parameters, including the permanent environmental effect for BW and body measurements (8758 records for each body measurement, as each fish was individually weighed and measured a maximum of six times). The second subset (2042 records for each trait) was used to estimate genetic correlations and heritabilities, which enabled the calculation of correlated response efficiencies between body measurements and the fillet traits. Heritability estimates across ages ranged from 0.05 to 0.5 for height, 0.02 to 0.48 for corrected length (CL), 0.05 to 0.68 for width, 0.08 to 0.57 for fillet weight (FW) and 0.12 to 0.42 for FY. All genetic correlation estimates between body measurements and FW were positive and strong (0.64 to 0.98). The estimates of genetic correlation between body measurements and FY were positive (except for CL at some ages), but weak to moderate (-0.08 to 0.68). These estimates resulted in strong and favorable correlated response efficiencies for FW and positive, but moderate for FY. These results indicate the possibility of achieving indirect genetic gains for FW and by selecting for morphometric traits, but low efficiency for FY when compared with direct selection.

  10. Solid-state nanopore localization by controlled breakdown of selectively thinned membranes

    NASA Astrophysics Data System (ADS)

    Carlsen, Autumn T.; Briggs, Kyle; Hall, Adam R.; Tabard-Cossa, Vincent

    2017-02-01

    We demonstrate precise positioning of nanopores fabricated by controlled breakdown (CBD) on solid-state membranes by spatially varying the electric field strength with localized membrane thinning. We show 100 × 100 nm2 precision in standard SiN x membranes (30-100 nm thick) after selective thinning by as little as 25% with a helium ion beam. Control over nanopore position is achieved through the strong dependence of the electric field-driven CBD mechanism on membrane thickness. Confinement of pore formation to the thinned region of the membrane is confirmed by TEM imaging and by analysis of DNA translocations. These results enhance the functionality of CBD as a fabrication approach and enable the production of advanced nanopore devices for single-molecule sensing applications.

  11. Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

    PubMed Central

    Poon, Art F. Y; Kosakovsky Pond, Sergei L.; Bennett, Phil; Richman, Douglas D; Leigh Brown, Andrew J.; Frost, Simon D. W

    2007-01-01

    CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design. PMID:17397261

  12. Molecular evolution of the endosperm starch synthesis pathway genes in rice (Oryza sativa L.) and its wild ancestor, O. rufipogon L.

    PubMed

    Yu, Guoqin; Olsen, Kenneth M; Schaal, Barbara A

    2011-01-01

    The evolution of metabolic pathways is a fundamental but poorly understood aspect of evolutionary change. One approach for understanding the complexity of pathway evolution is to examine the molecular evolution of genes that together comprise an integrated metabolic pathway. The rice endosperm starch biosynthetic pathway is one of the most thoroughly characterized metabolic pathways in plants, and starch is a trait that has evolved in response to strong selection during rice domestication. In this study, we have examined six key genes (AGPL2, AGPS2b, SSIIa, SBEIIb, GBSSI, ISA1) in the rice endosperm starch biosynthesis pathway to investigate the evolution of these genes before and after rice domestication. Genome-wide sequence tagged sites data were used as a neutral reference to overcome the problems of detecting selection in species with complex demographic histories such as rice. Five variety groups of Oryza sativa (aus, indica, tropical japonica, temperate japonica, aromatic) and its wild ancestor (O. rufipogon) were sampled. Our results showed evidence of purifying selection at AGPL2 in O. rufipogon and strong evidence of positive selection at GBSSI in temperate japonica and tropical japonica varieties and at GBSSI and SBEIIb in aromatic varieties. All the other genes showed a pattern consistent with neutral evolution in both cultivated rice and its wild ancestor. These results indicate the important role of positive selection in the evolution of starch genes during rice domestication. We discuss the role of SBEIIb and GBSSI in the evolution of starch quality during rice domestication and the power and limitation of detecting selection using genome-wide data as a neutral reference.

  13. Disentangling incentives effects of insurance coverage from adverse selection in the case of drug expenditure: a finite mixture approach.

    PubMed

    Munkin, Murat K; Trivedi, Pravin K

    2010-09-01

    This paper takes a finite mixture approach to model heterogeneity in incentive and selection effects of drug coverage on total drug expenditure among the Medicare elderly US population. Evidence is found that the positive drug expenditures of the elderly population can be decomposed into two groups different in the identified selection effects and interpreted as relatively healthy with lower average expenditures and relatively unhealthy with higher average expenditures, accounting for approximately 25 and 75% of the population, respectively. Adverse selection into drug insurance appears to be strong for the higher expenditure component and weak for the lower expenditure group. Copyright (c) 2010 John Wiley & Sons, Ltd.

  14. A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments.

    PubMed

    Yudin, Nikolay S; Larkin, Denis M; Ignatieva, Elena V

    2017-12-28

    Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals. After a search for publications containing keywords: "whole genome", "transcriptome or exome sequencing data", and "genome-wide genotyping array data" authors looked for information related to genetic signatures ascribable to positive selection in Arctic or Antarctic mammalian species. Publications related to Human, Arctic fox, Yakut horse, Mammoth, Polar bear, and Minke whale were chosen. The compendium of genes that potentially underwent positive selection in >1 of these six species consisted of 416 genes. Twelve of them showed traces of positive selection in three species. Gene ontology term enrichment analysis of 416 genes from the compendium has revealed 13 terms relevant to the scope of this study. We found that enriched terms were relevant to three major groups: terms associated with collagen proteins and the extracellular matrix; terms associated with the anatomy and physiology of cilium; terms associated with docking. We further revealed that genes from compendium were over-represented in the lists of genes expressed in the lung and liver. A compendium combining mammalian genes involved in adaptation to cold environment was designed, based on the intersection of positively selected genes from six Arctic and Antarctic species. The compendium contained 416 genes that have been positively selected in at least two species. However, we did not reveal any positively selected genes that would be related to cold adaptation in all species from our list. But, our work points to several strong candidate genes involved in mechanisms and biochemical pathways related to cold adaptation response in different species.

  15. Molecular evolution of the betagamma lens crystallin superfamily: evidence for a retained ancestral function in gamma N crystallins?

    PubMed

    Weadick, Cameron J; Chang, Belinda S W

    2009-05-01

    Within the vertebrate eye, betagamma crystallins are extremely stable lens proteins that are uniquely adapted to increase refractory power while maintaining transparency. Unlike alpha crystallins, which are well-characterized, multifunctional proteins that have important functions both in and out of the lens, betagamma lens crystallins are a diverse group of proteins with no clear ancestral or contemporary nonlens role. We carried out phylogenetic and molecular evolutionary analyses of the betagamma-crystallin superfamily in order to study the evolutionary history of the gamma N crystallins, a recently discovered, biochemically atypical family suggested to possess a divergent or ancestral function. By including nonlens, betagamma-motif-containing sequences in our analysis as outgroups, we confirmed the phylogenetic position of the gamma N family as sister to other gamma crystallins. Using maximum likelihood codon models to estimate lineage-specific nonsynonymous-to-synonymous rate ratios revealed strong positive selection in all of the early lineages within the betagamma family, with the striking exception of the lineage leading to the gamma N crystallins which was characterized by strong purifying selection. Branch-site analysis, used to identify candidate sites involved in functional divergence between gamma N crystallins and its sister clade containing all other gamma crystallins, identified several positively selected changes at sites of known functional importance in the betagamma crystallin protein structure. Further analyses of a fish-specific gamma N crystallin gene duplication revealed a more recent episode of positive selection in only one of the two descendant lineages (gamma N2). Finally, from the guppy, Poecilia reticulata, we isolated complete gamma N1 and gamma N2 coding sequence data from cDNA and partial coding sequence data from genomic DNA in order to confirm the presence of a novel gamma N2 intron, discovered through data mining of two pufferfish genomes. We conclude that the function of the gamma N family likely resembles the ancestral vertebrate betagamma crystallin more than other betagamma families. Furthermore, owing to the presence of an additional intron in some fish gamma N2 crystallins, and the inferred action of positive selection following the fish-specific gamma N duplication, we suggest that further study of fish gamma N crystallins will be critical in further elucidating possible ancestral functions of gamma N crystallins and any nonstructural role they may have.

  16. Habitat quality influences population distribution, individual space use and functional responses in habitat selection by a large herbivore.

    PubMed

    Bjørneraas, Kari; Herfindal, Ivar; Solberg, Erling Johan; Sæther, Bernt-Erik; van Moorter, Bram; Rolandsen, Christer Moe

    2012-01-01

    Identifying factors shaping variation in resource selection is central for our understanding of the behaviour and distribution of animals. We examined summer habitat selection and space use by 108 Global Positioning System (GPS)-collared moose in Norway in relation to sex, reproductive status, habitat quality, and availability. Moose selected habitat types based on a combination of forage quality and availability of suitable habitat types. Selection of protective cover was strongest for reproducing females, likely reflecting the need to protect young. Males showed strong selection for habitat types with high quality forage, possibly due to higher energy requirements. Selection for preferred habitat types providing food and cover was a positive function of their availability within home ranges (i.e. not proportional use) indicating functional response in habitat selection. This relationship was not found for unproductive habitat types. Moreover, home ranges with high cover of unproductive habitat types were larger, and smaller home ranges contained higher proportions of the most preferred habitat type. The distribution of moose within the study area was partly related to the distribution of different habitat types. Our study shows how distribution and availability of habitat types providing cover and high-quality food shape ungulate habitat selection and space use.

  17. A Comparative Case Study of Self-Actualization in Eleanor Roosevelt and Antoine de Saint-Exupery.

    ERIC Educational Resources Information Center

    Tyska, Cynthia Ann

    Eleanor Roosevelt and Antoine de Saint-Exupery are described as strongly developed self-actualizing people. They were selected as subjects of this study because they are generally believed to possess self-actualizing characteristics and because their positions as public figures made it more likely that data on them would be accessible.…

  18. Positive selection in the N-terminal extramembrane domain of lung surfactant protein C (SP-C) in marine mammals.

    PubMed

    Foot, Natalie J; Orgeig, Sandra; Donnellan, Stephen; Bertozzi, Terry; Daniels, Christopher B

    2007-07-01

    Maximum-likelihood models of codon and amino acid substitution were used to analyze the lung-specific surfactant protein C (SP-C) from terrestrial, semi-aquatic, and diving mammals to identify lineages and amino acid sites under positive selection. Site models used the nonsynonymous/synonymous rate ratio (omega) as an indicator of selection pressure. Mechanistic models used physicochemical distances between amino acid substitutions to specify nonsynonymous substitution rates. Site models strongly identified positive selection at different sites in the polar N-terminal extramembrane domain of SP-C in the three diving lineages: site 2 in the cetaceans (whales and dolphins), sites 7, 9, and 10 in the pinnipeds (seals and sea lions), and sites 2, 9, and 10 in the sirenians (dugongs and manatees). The only semi-aquatic contrast to indicate positive selection at site 10 was that including the polar bear, which had the largest body mass of the semi-aquatic species. Analysis of the biophysical properties that were influential in determining the amino acid substitutions showed that isoelectric point, chemical composition of the side chain, polarity, and hydrophobicity were the crucial determinants. Amino acid substitutions at these sites may lead to stronger binding of the N-terminal domain to the surfactant phospholipid film and to increased adsorption of the protein to the air-liquid interface. Both properties are advantageous for the repeated collapse and reinflation of the lung upon diving and resurfacing and may reflect adaptations to the high hydrostatic pressures experienced during diving.

  19. Detection of Listeria monocytogenes in pork and beef using the VIDAS® LMO2 automated enzyme linked immunoassay method.

    PubMed

    Meyer, Cornelia; Fredriksson-Ahomaa, Maria; Sperner, Brigitte; Märtlbauer, Erwin

    2011-07-01

    Listeria (L.) monocytogenes, a foodborne pathogen, is known to be a possible contaminant of foods during production and processing. Samples (n=985) of raw meat and by-products obtained from beef and pork were first screened by the VIDAS system for the presence of Listeria spp., followed by testing for the presence of L. monocytogenes. Positive L. monocytogenes results were confirmed by plating on selective agars: 14% of the samples were positive for Listeria and 4% tested positive for L. monocytogenes, of which 3% were confirmed on selective agars. In by-products (17%) the contamination with listeriae was higher than in meat cuts (10%). Only samples strongly positive for Listeria spp. by VIDAS were positive for L. monocytogenes. Overall, the prevalence of L. monocytogenes in beef and pork samples was rather low in comparison to most previous studies. The VIDAS system was shown to be a suitable method for screening out Listeria-negative samples; the main advantage being a markedly reduced assay time. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Conceptualizing and Measuring Intergenerational Ambivalence in Later Life

    PubMed Central

    Gilligan, Megan; Pillemer, Karl

    2011-01-01

    Objectives. In this paper, we explored the association between direct and indirect measures of intergenerational ambivalence, making comparisons by generational position and child’s gender; furthermore, we examined whether these measures were similarly strong predictors of depressive symptoms and positive affect. Methods. Data for the analysis were collected from 254 mothers aged 72–82 years and a randomly selected adult child as part of a larger study of within-family differences in parent–adult child relations. Results. The findings provided evidence that direct and indirect measures were strongly associated among mothers but only weakly associated among adult children, particularly sons. The two measures were similarly strong predictors of mothers’, but not children’s, depressive symptoms and positive affect. The most pronounced differences in congruence between direct and indirect measures were found when comparing mothers and sons. Discussion. The analyses presented here suggest that direct and indirect measures of intergenerational ambivalence may not be tapping the same underlying construct, particularly in the case of adult children and especially sons. Furthermore, direct measures may have an advantage over indirect measures when including sons in the study design. We conclude that direct and indirect measures cannot be used interchangeably across the combination of generation and gender. PMID:22002969

  1. The interplay between the Aharonov-Bohm interference and parity selective tunneling in graphene nanoribbon rings.

    PubMed

    Nguyen, V Hung; Niquet, Y-M; Dollfus, P

    2014-05-21

    We report on a numerical study of the Aharonov-Bohm (AB) effect and parity selective tunneling in pn junctions based on rectangular graphene rings where the contacts and ring arms are all made of zigzag nanoribbons. We find that when applying a magnetic field to the ring, the AB interference can reverse the parity symmetry of incoming waves and hence can strongly modulate the parity selective transmission through the system. Therefore, the transmission between two states of different parity exhibits the AB oscillations with a π-phase shift, compared to the case of states of the same parity. On this basis, it is shown that interesting effects, such as giant (both positive and negative) magnetoresistance and strong negative differential conductance, can be achieved in this structure. Our study thus presents a new property of the AB interference in graphene nanorings, which could be helpful for further understanding the transport properties of graphene mesoscopic systems.

  2. Tissue culture specificity of the tobacco ASA2 promoter driving hpt as a selectable marker for soybean transformation selection.

    PubMed

    Zernova, Olga; Zhong, Wei; Zhang, Xing-Hai; Widholm, Jack

    2008-11-01

    This study was carried out to determine if the tobacco anthranilate synthase ASA2 2.3 kb promoter drives tissue culture specific expression and if it is strong enough to drive hpt (hygromycin phosphotransferase) gene expression at a level sufficient to allow selection of transformed soybean embryogenic culture lines. A number of transformed cell lines were selected showing that the promoter was strong enough. Northern blot analysis of plant tissues did not detect hpt mRNA in the untransformed control or in the ASA2-hpt plants except in developing seeds while hpt mRNA was detected in all tissues of the CaMV35S-hpt positive control line plants. However, when the more sensitive RT-PCR assay was used all tissues of the ASA2-hpt plants except roots and mature seeds were found to contain detectable hpt mRNA. Embryogenic tissue cultures initiated from the ASA2-hpt plants contained hpt mRNA detectable by both northern and RT-PCR analysis and the cultures were hygromycin resistant. Friable callus initiated from leaves of ASA2-hpt plants did in some cases contain hpt mRNA that was only barely detectable by northern hybridization even though the callus was very hygromycin resistant. Thus the ASA2 promoter is strong enough to drive sufficient hpt expression in soybean embryogenic cultures for hygromycin selection and only very low levels of expression were found in most plant tissues with none in mature seeds.

  3. Sexual selection and the adaptive evolution of PKDREJ protein in primates and rodents.

    PubMed

    Vicens, Alberto; Gómez Montoto, Laura; Couso-Ferrer, Francisco; Sutton, Keith A; Roldan, Eduardo R S

    2015-02-01

    PKDREJ is a testis-specific protein thought to be located on the sperm surface. Functional studies in the mouse revealed that loss of PKDREJ has effects on sperm transport and the ability to undergo an induced acrosome reaction. Thus, PKDREJ has been considered a potential target of post-copulatory sexual selection in the form of sperm competition. Proteins involved in reproductive processes often show accelerated evolution. In many cases, this rapid divergence is promoted by positive selection which may be driven, at least in part, by post-copulatory sexual selection. We analysed the evolution of the PKDREJ protein in primates and rodents and assessed whether PKDREJ divergence is associated with testes mass relative to body mass, which is a reliable proxy of sperm competition levels. Evidence of an association between the evolutionary rate of the PKDREJ gene and testes mass relative to body mass was not found in primates. Among rodents, evidence of positive selection was detected in the Pkdrej gene in the family Cricetidae but not in Muridae. We then assessed whether Pkdrej divergence is associated with episodes of sperm competition in these families. We detected a positive significant correlation between the evolutionary rates of Pkdrej and testes mass relative to body mass in cricetids. These findings constitute the first evidence of post-copulatory sexual selection influencing the evolution of a protein that participates in the mechanisms regulating sperm transport and the acrosome reaction, strongly suggesting that positive selection may act on these fertilization steps, leading to advantages in situations of sperm competition. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Effects of protein transduction domain (PTD) selection and position for improved intracellular delivery of PTD-Hsp27 fusion protein formulations.

    PubMed

    Ul Ain, Qurrat; Lee, Jong Hwan; Woo, Young Sun; Kim, Yong-Hee

    2016-09-01

    Protein drugs have attracted considerable attention as therapeutic agents due to their diversity and biocompatibility. However, hydrophilic proteins possess difficulty in penetrating lipophilic cell membrane. Although protein transduction domains (PTDs) have shown effectiveness in protein delivery, the importance of selection and position of PTDs in recombinant protein vector constructs has not been investigated. This study intends to investigate the significance of PTD selection and position for therapeutic protein delivery. Heat shock protein 27 (Hsp27) would be a therapeutic protein for the treatment of ischemic heart diseases, but itself is insufficient to prevent systemic degradation and overcoming biochemical barriers during cellular transport. Among all PTD-Hsp27 fusion proteins we cloned, Tat-Hsp27 fusion protein showed the highest efficacy. Nona-arginine (9R) conjugation to the N-terminal of Hsp27 (Hsp27-T) showed higher efficacy than C-terminal. To test the synergistic effect of two PTDs, Tat was inserted to the N-terminal of Hsp27-9R. Tat-Hsp27-9R exhibited enhanced transduction efficiency and significant improvement against oxidative stress and apoptosis. PTD-Hsp27 fusion proteins have strong potential to be developed as therapeutic proteins for the treatment of ischemic heart diseases and selection and position of PTDs for improved efficacy of PTD-fusion proteins need to be optimized considering protein's nature, transduction efficiency and stability.

  5. Evaluating the performance of selection scans to detect selective sweeps in domestic dogs

    PubMed Central

    Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R.; Messer, Philipp W.

    2015-01-01

    Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analyzed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used, and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. PMID:26589239

  6. Evaluating the performance of selection scans to detect selective sweeps in domestic dogs.

    PubMed

    Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R; Messer, Philipp W

    2016-01-01

    Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analysed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. © 2015 John Wiley & Sons Ltd.

  7. X-Ray Properties of Lensing-Selected Clusters

    NASA Astrophysics Data System (ADS)

    Paterno-Mahler, Rachel; Sharon, Keren; Bayliss, Matthew; McDonald, Michael; Gladders, Michael; Johnson, Traci; Dahle, Hakon; Rigby, Jane R.; Whitaker, Katherine E.; Florian, Michael; Wuyts, Eva

    2017-08-01

    I will present preliminary results from the Michigan Swift X-ray observations of clusters from the Sloan Giant Arcs Survey (SGAS). These clusters were lensing selected based on the presence of a giant arc visible from SDSS. I will characterize the morphology of the intracluster medium (ICM) of the clusters in the sample, and discuss the offset between the X-ray centroid, the mass centroid as determined by strong lensing analysis, and the BCG position. I will also present early-stage work on the scaling relation between the lensing mass and the X-ray luminosity.

  8. Molecular evolution of psbA gene in ferns: unraveling selective pressure and co-evolutionary pattern

    PubMed Central

    2012-01-01

    Background The photosynthetic oxygen-evolving photo system II (PS II) produces almost the entire oxygen in the atmosphere. This unique biochemical system comprises a functional core complex that is encoded by psbA and other genes. Unraveling the evolutionary dynamics of this gene is of particular interest owing to its direct role in oxygen production. psbA underwent gene duplication in leptosporangiates, in which both copies have been preserved since. Because gene duplication is often followed by the non-fictionalization of one of the copies and its subsequent erosion, preservation of both psbA copies pinpoint functional or regulatory specialization events. The aim of this study was to investigate the molecular evolution of psbA among fern lineages. Results We sequenced psbA , which encodes D1 protein in the core complex of PSII, in 20 species representing 8 orders of extant ferns; then we searched for selection and convolution signatures in psbA across the 11 fern orders. Collectively, our results indicate that: (1) selective constraints among D1 protein relaxed after the duplication in 4 leptosporangiate orders; (2) a handful positively selected codons were detected within species of single copy psbA, but none in duplicated ones; (3) a few sites among D1 protein were involved in co-evolution process which may intimate significant functional/structural communications between them. Conclusions The strong competition between ferns and angiosperms for light may have been the main cause for a continuous fixation of adaptive amino acid changes in psbA , in particular after its duplication. Alternatively, a single psbA copy may have undergone bursts of adaptive changes at the molecular level to overcome angiosperms competition. The strong signature of positive Darwinian selection in a major part of D1 protein is testament to this. At the same time, species own two psbA copies hardly have positive selection signals among the D1 protein coding sequences. In this study, eleven co-evolving sites have been detected via different molecules, which may be more important than others. PMID:22899792

  9. Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y.

    PubMed

    Wilde, Sandra; Timpson, Adrian; Kirsanow, Karola; Kaiser, Elke; Kayser, Manfred; Unterländer, Martina; Hollfelder, Nina; Potekhina, Inna D; Schier, Wolfram; Thomas, Mark G; Burger, Joachim

    2014-04-01

    Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways--HERC2, SLC45A2, and TYR--using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2-10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y.

  10. Accelerated evolution of CES7, a gene encoding a novel major urinary protein in the cat family.

    PubMed

    Li, Gang; Janecka, Jan E; Murphy, William J

    2011-02-01

    Cauxin is a novel urinary protein recently identified in the domestic cat that regulates the excretion of felinine, a pheromone precursor involved in sociochemical communication and territorial marking of domestic and wild felids. Understanding the evolutionary history of cauxin may therefore illuminate molecular adaptations involved in the evolution of pheromone-based communication, recognition, and mate selection in wild animals. We sequenced the gene encoding cauxin, CES7, in 22 species representing all major felid lineages, and multiple outgroups and showed that it has undergone rapid evolutionary change preceding and during the diversification of the cat family. A comparison between feline cauxin and orthologous carboxylesterases from other mammalian lineages revealed evidence of strong positive Darwinian selection within and between several cat lineages, enriched at functionally important sites of the protein. The higher rate of radical amino acid replacements in small felids, coupled with the lack of felinine and extremely low levels of cauxin in the urine of the great cats (Panthera), correlates with functional divergence of this gene in Panthera, and its putative loss in the snow leopard. Expression studies found evidence for several alternatively spliced transcripts in testis and brain, suggesting additional roles in male reproductive fitness and behavior. Our work presents the first report of strong positive natural selection acting on a major urinary protein of nonrodent mammals, providing evidence for parallel selection pressure on the regulation of pheromones in different mammalian lineages, despite the use of different metabolic pathways. Our results imply that natural selection may drive rapid changes in the regulation of pheromones in urine among the different cat species, which in turn may influence social behavior, such as territorial marking and conspecific recognition, therefore serving as an important mechanism for the radiation of this group of mammals.

  11. Spruce Budworm (Choristoneura fumiferana) Performance in Relation to Foliar Chemistry of its Host Plants

    Treesearch

    William John.  Mattson

    1983-01-01

    Spruce budworm growth was best on balsam fir, poorest on lowland black spruce, and intermediate on upland white and black spruce. Growth was consistently, positively linked to foliar N and negatively linked to Fe, K, and select terpenes. Survival rates were not strongly, nor consistently linked to any of the measured foliar chemical traits.

  12. Female-selective abortion in Asia: patterns, policies, and debates.

    PubMed

    Miller, B D

    2001-12-01

    Since the early 1980s, the use of sex-selective abortion increased in many Asian contexts. Estimates indicate that several million female fetuses were aborted in the last two decades of the twentieth century. This article takes a currently unusual approach for a cultural anthropologist in pursuing cross-national comparisons of trends in sex-selective abortion. The risks involved in such an approach are taken in the hope that it will yield insights not gained through localized analysis. After reviewing the available evidence on female-selective abortion, I discuss features of Asian culture that support strong son preference. Next I review the related issues of increased technological availability for prenatal sex selection and national policies about sex selection. Last, I consider several positions on female-selective abortion and how cultural anthropology may contribute to understanding the global context and consequences of prenatal gender discrimination.

  13. Inoculum selection is crucial to ensure operational stability in anaerobic digestion.

    PubMed

    De Vrieze, Jo; Gildemyn, Sylvia; Vilchez-Vargas, Ramiro; Jáuregui, Ruy; Pieper, Dietmar H; Verstraete, Willy; Boon, Nico

    2015-01-01

    Anaerobic digestion is considered a key technology for the future bio-based economy. The microbial consortium carrying out the anaerobic digestion process is quite complex, and its exact role in terms of "elasticity", i.e., the ability to rapidly adapt to changing conditions, is still unknown. In this study, the role of the initial microbial community in terms of operational stability and stress tolerance was evaluated during a 175-day experiment. Five different inocula from stable industrial anaerobic digesters were fed a mixture of waste activated sludge and glycerol. Increasing ammonium pulses were applied to evaluate stability and stress tolerance. A different response in terms of start-up and ammonium tolerance was observed among the different inocula. Methanosaetaceae were the dominant acetoclastic methanogens, yet, Methanosarcinaceae increased in abundance at elevated ammonium concentrations. A shift from a Firmicutes to a Proteobacteria dominated bacterial community was observed in failing digesters. Methane production was strongly positively correlated with Methanosaetaceae, but also with Bacteria related to Anaerolinaceae, Clostridiales, and Alphaproteobacteria. Volatile fatty acids were strongly positively correlated with Betaproteobacteria and Bacteroidetes, yet ammonium concentration only with Bacteroidetes. Overall, these results indicate the importance of inoculum selection to ensure stable operation and stress tolerance in anaerobic digestion.

  14. Size evolution in microorganisms masks trade-offs predicted by the growth rate hypothesis.

    PubMed

    Gounand, Isabelle; Daufresne, Tanguy; Gravel, Dominique; Bouvier, Corinne; Bouvier, Thierry; Combe, Marine; Gougat-Barbera, Claire; Poly, Franck; Torres-Barceló, Clara; Mouquet, Nicolas

    2016-12-28

    Adaptation to local resource availability depends on responses in growth rate and nutrient acquisition. The growth rate hypothesis (GRH) suggests that growing fast should impair competitive abilities for phosphorus and nitrogen due to high demand for biosynthesis. However, in microorganisms, size influences both growth and uptake rates, which may mask trade-offs and instead generate a positive relationship between these traits (size hypothesis, SH). Here, we evolved a gradient of maximum growth rate (μ max ) from a single bacterium ancestor to test the relationship among μ max , competitive ability for nutrients and cell size, while controlling for evolutionary history. We found a strong positive correlation between μ max and competitive ability for phosphorus, associated with a trade-off between μ max and cell size: strains selected for high μ max were smaller and better competitors for phosphorus. Our results strongly support the SH, while the trade-offs expected under GRH were not apparent. Beyond plasticity, unicellular populations can respond rapidly to selection pressure through joint evolution of their size and maximum growth rate. Our study stresses that physiological links between these traits tightly shape the evolution of competitive strategies. © 2016 The Author(s).

  15. Sex difference in attractiveness perceptions of strong and weak male walkers.

    PubMed

    Fink, Bernhard; André, Selina; Mines, Johanna S; Weege, Bettina; Shackelford, Todd K; Butovskaya, Marina L

    2016-11-01

    Men and women accurately assess male physical strength from facial and body morphology cues. Women's assessments of male facial attractiveness, masculinity, and dominance correlate positively with male physical strength. A positive relationship also has been reported between physical strength and attractiveness of men's dance movements. Here, we investigate men's and women's attractiveness, dominance, and strength assessments from brief samples of male gait. Handgrip strength (HGS) was measured in 70 heterosexual men and their gait was motion-captured. Men and women judged 20 precategorized strong (high HGS) and weak (low HGS) walkers on attractiveness, dominance, and strength, and provided a measure of their own HGS. Both men and women judged strong walkers higher on dominance and strength than weak walkers. Women but not men judged strong walkers more attractive than weak walkers. These effects were independent of observers' physical strength. Male physical strength is conveyed not only through facial and body morphology, but also through body movements. We discuss our findings with reference to studies suggesting that physical strength provides information about male quality in contexts of inter- and intrasexual selection. Am. J. Hum. Biol. 28:913-917, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. The roles of chronological age and time perspective in memory positivity.

    PubMed

    Kan, Irene P; Garrison, Shaina L; Drummey, Anna B; Emmert, Brian E; Rogers, Leeland L

    2018-07-01

    The observation that older adults show enhanced cognition for emotionally positive information has been labeled the positivity effect (Reed, Chan, & Mikels, 2014). According to the Socioemotional Selectivity Theory (SST, Carstensen, 1991), a prominent lifespan development theory, cognition is strongly influenced by motivational goals, and these goals are impacted by subjective time perspective. Although the positivity effect is most commonly observed in older adults, as age usually co-varies with time perspective, the SST posits that time perspective, not age, is the key explanatory factor of positivity. We examined the effects of these predictors on positivity in an episodic memory task in younger and older adults and found that age, not time perspective, was a key predictor of memory positivity. Our results add to the growing literature that challenge the notion that time perspective is the driving force behind age-related differences in emotional processing and functioning.

  17. Genetic signature of natural selection in first Americans

    PubMed Central

    G. Amorim, Carlos Eduardo; Nunes, Kelly; Meyer, Diogo; Comas, David; Bortolini, Maria Cátira; Salzano, Francisco Mauro; Hünemeier, Tábita

    2017-01-01

    When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments. PMID:28193867

  18. Studying the genetic basis of speciation in high gene flow marine invertebrates

    PubMed Central

    2016-01-01

    A growing number of genes responsible for reproductive incompatibilities between species (barrier loci) exhibit the signals of positive selection. However, the possibility that genes experiencing positive selection diverge early in speciation and commonly cause reproductive incompatibilities has not been systematically investigated on a genome-wide scale. Here, I outline a research program for studying the genetic basis of speciation in broadcast spawning marine invertebrates that uses a priori genome-wide information on a large, unbiased sample of genes tested for positive selection. A targeted sequence capture approach is proposed that scores single-nucleotide polymorphisms (SNPs) in widely separated species populations at an early stage of allopatric divergence. The targeted capture of both coding and non-coding sequences enables SNPs to be characterized at known locations across the genome and at genes with known selective or neutral histories. The neutral coding and non-coding SNPs provide robust background distributions for identifying FST-outliers within genes that can, in principle, identify specific mutations experiencing diversifying selection. If natural hybridization occurs between species, the neutral coding and non-coding SNPs can provide a neutral admixture model for genomic clines analyses aimed at finding genes exhibiting strong blocks to introgression. Strongylocentrotid sea urchins are used as a model system to outline the approach but it can be used for any group that has a complete reference genome available. PMID:29491951

  19. Subtle differences in selective pressures applied on the envelope gene of HIV-1 in pregnant versus non-pregnant women.

    PubMed

    Ransy, Doris G; Lord, Etienne; Caty, Martine; Lapointe, Normand; Boucher, Marc; Diallo, Abdoulaye Baniré; Soudeyns, Hugo

    2018-04-17

    Pregnancy is associated with modulations of maternal immunity that contribute to foeto-maternal tolerance. To understand whether and how these alterations impact antiviral immunity, a detailed cross-sectional analysis of selective pressures exerted on HIV-1 envelope amino-acid sequences was performed in a group of pregnant (n = 32) and non-pregnant (n = 44) HIV-infected women in absence of treatment with antiretroviral therapy (ART). Independent of HIV-1 subtype, p-distance, dN and dS were all strongly correlated with one another but were not significantly different in pregnant as compared to non-pregnant patients. Differential levels of selective pressure applied on different Env subdomains displayed similar yet non-identical patterns between the two groups, with pressure applied on C1 being significantly lower in constant regions C1 and C2 than in V1, V2, V3 and C3. To draw a general picture of the selection applied on the envelope and compensate for inter-individual variations, we performed a binomial test on selection frequency data pooled from pregnant and non-pregnant women. This analysis uncovered 42 positions, present in both groups, exhibiting statistically-significant frequency of selection that invariably mapped to the surface of the Env protein, with the great majority located within epitopes recognized by Env-specific antibodies or sites associated with the development of cross-reactive neutralizing activity. The median frequency of occurrence of positive selection per site was significantly lower in pregnant versus non-pregnant women. Furthermore, examination of the distribution of positively selected sites using a hypergeometric test revealed that only 2 positions (D137 and S142) significantly differed between the 2 groups. Taken together, these result indicate that pregnancy is associated with subtle yet distinctive changes in selective pressures exerted on the HIV-1 Env protein that are compatible with transient modulations of maternal immunity. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Somatic Mutation Patterns in Hemizygous Genomic Regions Unveil Purifying Selection during Tumor Evolution

    PubMed Central

    Basu, Swaraj; Larsson, Erik

    2016-01-01

    Identification of cancer driver genes using somatic mutation patterns indicative of positive selection has become a major goal in cancer genomics. However, cancer cells additionally depend on a large number of genes involved in basic cellular processes. While such genes should in theory be subject to strong purifying (negative) selection against damaging somatic mutations, these patterns have been elusive and purifying selection remains inadequately explored in cancer. Here, we hypothesized that purifying selection should be evident in hemizygous genomic regions, where damaging mutations cannot be compensated for by healthy alleles. Using a 7,781-sample pan-cancer dataset, we first confirmed this in POLR2A, an essential gene where hemizygous deletions are known to confer elevated sensitivity to pharmacological suppression. We next used this principle to identify several genes and pathways that show patterns indicative of purifying selection to avoid deleterious mutations. These include the POLR2A interacting protein INTS10 as well as genes involved in mRNA splicing, nonsense-mediated mRNA decay and other RNA processing pathways. Many of these genes belong to large protein complexes, and strong overlaps were observed with recent functional screens for gene essentiality in human cells. Our analysis supports that purifying selection acts to preserve the remaining function of many hemizygously deleted essential genes in tumors, indicating vulnerabilities that might be exploited by future therapeutic strategies. PMID:28027311

  1. EGFR, KRAS, and BRAF mutational profiles of female patients with micropapillary predominant invasive lung adenocarcinoma

    PubMed

    Demirağ, Funda; Yılmaz, Aydın; Yılmaz Demirci, Nilgün; Yılmaz, Ülkü; Erdoğan, Yurdanur

    2017-11-13

    Background/aim: This study aimed to analyze EGFR, KRAS, and BRAF mutations in females with micropapillary predominant invasive lung adenocarcinoma and their relationships with immunohistochemical and clinicopathological patterns.Materials and methods: A total of 15 females with micropapillary lung adenocarcinoma were selected. Mutational analysis of the EGFR, KRAS, and BRAF genes was carried out. Information regarding the demographic data, tumor size, treatment, and survival time for each patient was collated, and the predominant cell type, secondary architectural growth patterns, psammoma bodies, necrosis, and visceral pleural and angiolymphatic invasions were evaluated.Results: We identified EGFR mutation in six cases, KRAS mutation in three cases, and BRAF mutation in one case. EGFR, c-kit, VEGFR, and bcl-2 positivity was observed in ten, seven, four, and six cases, respectively. All cases were positive for VEGF (strong positivity in 11 cases and weak positivity in four cases) and bcl-2 (strong positivity in nine cases and weak positivity in six cases). Seven (46.6%) cases were positive for c-kit and 10 (66.6%) cases were positive for EGFR. Conclusion: EGFR mutation occurred at a higher incidence rate in micropapillary predominant invasive adenocarcinoma than has previously been found in conventional lung adenocarcinomas. KRAS mutation was observed as having a similar frequency to what was previously observed, but the frequency of BRAF mutation was lower than previously reported.

  2. Characterizing Responses of Translation Invariant Neurons to Natural Stimuli: Maximally Informative Invariant Dimensions

    PubMed Central

    Eickenberg, Michael; Rowekamp, Ryan J.; Kouh, Minjoon; Sharpee, Tatyana O.

    2012-01-01

    Our visual system is capable of recognizing complex objects even when their appearances change drastically under various viewing conditions. Especially in the higher cortical areas, the sensory neurons reflect such functional capacity in their selectivity for complex visual features and invariance to certain object transformations, such as image translation. Due to the strong nonlinearities necessary to achieve both the selectivity and invariance, characterizing and predicting the response patterns of these neurons represents a formidable computational challenge. A related problem is that such neurons are poorly driven by randomized inputs, such as white noise, and respond strongly only to stimuli with complex high-order correlations, such as natural stimuli. Here we describe a novel two-step optimization technique that can characterize both the shape selectivity and the range and coarseness of position invariance from neural responses to natural stimuli. One step in the optimization involves finding the template as the maximally informative dimension given the estimated spatial location where the response could have been triggered within each image. The estimates of the locations that triggered the response are subsequently updated in the next step. Under the assumption of a monotonic relationship between the firing rate and stimulus projections on the template at a given position, the most likely location is the one that has the largest projection on the estimate of the template. The algorithm shows quick convergence during optimization, and the estimation results are reliable even in the regime of small signal-to-noise ratios. When we apply the algorithm to responses of complex cells in the primary visual cortex (V1) to natural movies, we find that responses of the majority of cells were significantly better described by translation invariant models based on one template compared with position-specific models with several relevant features. PMID:22734487

  3. A mechanistic assessment of seasonal microhabitat selection by drift-feeding rainbow trout Oncorhynchus mykiss in a southwestern headwater stream

    USGS Publications Warehouse

    Kalb, Bradley W.; Huntsman, Brock M.; Caldwell, Colleen A.; Bozek, Michael A.

    2018-01-01

    The positioning of fishes within a riverscape is dependent on the proximity of complementary habitats. In this study, foraging and non-foraging habitat were quantified monthly over an entire year for a rainbow trout (Oncorhynchus mykiss) population in an isolated, headwater stream in southcentral New Mexico. The stream follows a seasonal thermal and hydrologic pattern typical for a Southwestern stream and was deemed suitable for re-introduction of the native and close relative, Rio Grande cutthroat trout (O. clarkii virginalis). However, uncertainty associated with limited habitat needed to be resolved if repatriation of the native fish was to be successful. Habitat was evaluated using resource selection functions with a mechanistic drift-foraging model to explain trout distributions. Macroinvertebrate drift was strongly season- and temperature-dependent (lower in winter and spring, higher in summer and fall). Models identified stream depth as the most limiting factor for habitat selection across seasons and size-classes. Additionally, positions closer to cover were selected during the winter by smaller size-classes (0, 1, 2), while net energy intake was important during the spring for most size-classes (0, 1, 2, 3). Drift-foraging models identified that 81% of observed trout selected positions that could meet maintenance levels throughout the year. Moreover, 40% of selected habitats could sustain maximum growth. Stream positions occupied by rainbow trout were more energetically profitable than random sites regardless of season or size-class. Larger size-classes (3, 4+) were energetically more limited throughout the year than were smaller size-classes. This research suggests that habitat in the form of deep pools is of paramount importance for rainbow trout or native cutthroat trout.

  4. Gene conversion and positive selection driving the evolution of the Caenorhabditis ssp. ZIM/HIM-8 protein family.

    PubMed

    Liu, Qingpo

    2009-03-01

    In C. elegans, four C2H2 zinc-finger proteins (ZIM-1, ZIM-2, ZIM-3, and HIM-8), which are arranged in tandem, mediate chromosome-specific pairing and synapsis during meiosis. The zim/him-8 genes from three Caenorhabditis species were contrasted in an effort to investigate the mechanisms driving their evolution. Here it is shown that the preservation of higher degree of sequence similarity in the N-terminal portion, particularly in several regions within the second exon between paralogous zim genes (especially between zim-1 and zim-3), is due to independent interparalogue gene conversions. However, the evolutionary force is not uniformly strong across species. The present data reveal that more frequent gene conversion events have occurred in C. elegans, whereas only gene conversions between zim-1 and zim-3 are detected in C. remanei. Although gene conversions are predicted to be present among zim-1, zim-2, and zim-3 in C. briggsae, the conversion tracts between zim-1/zim-2 and zim-2/zim-3 are very short. Moreover, positive selection analysis was performed on the basis of the significantly discordant phylogenies reconstructed using the N- and C-terminal sequences, respectively. Several codon sites located in the regions that are supposed not to have experienced gene conversions are predicted to be under the influence of positive selection. In comparison, stronger positive selection has acted on the C-terminal region relative to the N-terminal region. Thus, the zim/him-8 genes that evolve concertedly have also been shown to undergo adaptive diversifying selection.

  5. Plant selection and soil legacy enhance long-term biodiversity effects.

    PubMed

    Zuppinger-Dingley, Debra; Flynn, Dan F B; De Deyn, Gerlinde B; Petermann, Jana S; Schmid, Bernhard

    2016-04-01

    Plant-plant and plant-soil interactions can help maintain plant diversity and ecosystem functions. Changes in these interactions may underlie experimentally observed increases in biodiversity effects over time via the selection of genotypes adapted to low or high plant diversity. Little is known, however, about such community-history effects and particularly the role of plant-soil interactions in this process. Soil-legacy effects may occur if co-evolved interactions with soil communities either positively or negatively modify plant biodiversity effects. We tested how plant selection and soil legacy influence biodiversity effects on productivity, and whether such effects increase the resistance of the communities to invasion by weeds. We used two plant selection treatments: parental plants growing in monoculture or in mixture over 8 yr in a grassland biodiversity experiment in the field, which we term monoculture types and mixture types. The two soil-legacy treatments used in this study were neutral soil inoculated with live or sterilized soil inocula collected from the same plots in the biodiversity experiment. For each of the four factorial combinations, seedlings of eight species were grown in monocultures or four-species mixtures in pots in an experimental garden over 15 weeks. Soil legacy (live inoculum) strongly increased biodiversity complementarity effects for communities of mixture types, and to a significantly weaker extent for communities of monoculture types. This may be attributed to negative plant-soil feedbacks suffered by mixture types in monocultures, whereas monoculture types had positive plant-soil feedbacks, in both monocultures and mixtures. Monocultures of mixture types were most strongly invaded by weeds, presumably due to increased pathogen susceptibility, reduced biomass, and altered plant-soil interactions of mixture types. These results show that biodiversity effects in experimental grassland communities can be modified by the evolution of positive vs. negative plant-soil feedbacks of plant monoculture vs. mixture types.

  6. A Small Aptamer with Strong and Specific Recognition of the Triphosphate of ATP

    PubMed Central

    Sazani, Peter L.; Larralde, Rosa

    2004-01-01

    We report the in vitro selection of an RNA-based ATP aptamer with the ability to discriminate between adenosine ligands based on their 5‘ phosphorylation state. Previous selection of ATP aptamers yielded molecules that do not significantly discriminate between ligands at the 5‘ position. By applying a selective pressure that demands recognition of the 5‘ triphosphate, we obtained an aptamer that binds to ATP with a Kd of approximately 5 μM, and to AMP with a Kd of approximately 5.5 mM, a difference of 1100-fold. This aptamer demonstrates the ability of small RNAs to interact with negatively charged moieties. PMID:15237981

  7. Meta-analysis of age and skill effects on recalling chess positions and selecting the best move.

    PubMed

    Moxley, Jerad H; Charness, Neil

    2013-10-01

    A meta-analysis was conducted of studies that measured the effects of both age and skill in chess on the tasks of selecting the best move for chess positions (the best move task) as well as recalling chess game positions (the recall task). Despite a small sample of studies, we demonstrated that there are age and skill effects on both tasks: age being negatively associated with performance on both tasks and skill being positively associated with performance on both tasks. On the best move task, we found that skill was the dominant effect, while on the recall task, skill and age were approximately equally strong effects. We also found that skill was best measured by the best move task. In the case of the best move task, this result is consistent with the argument that it accurately replicates expert performance (Ericsson & Smith, 1991). Results for the recall task argue that this task captures effects related to skill, but also effects likely due to a general aging process. Implications for our understanding of aging in skilled domains are also discussed.

  8. Evolution of mating system and the genetic covariance between male and female investment in Clarkia (onagraceae): selfing opposes the evolution of trade-offs.

    PubMed

    Mazer, Susan J; Delesalle, Véronique A; Paz, Horacio

    2007-01-01

    Sex allocation theory has assumed that hermaphroditic species exhibit strong genetically based trade-offs between investment in male and female function. The potential effects of mating system on the evolution of this genetic covariance, however, have not been explored. We have challenged the assumption of a ubiquitous trade-off between male and female investment by arguing that in highly self-fertilizing species, stabilizing natural selection should favor highly efficient ratios of male to female gametes. In flowering plants, the result of such selection would be similar pollen:ovule (P:O) ratios across selfing genotypes, precluding a negative genetic correlation (r(g)) between pollen and ovule production per flower. Moreover, if selfing genotypes with similar P:O ratios differ in total gametic investment per flower, a positive r(g) between pollen and ovule production would be observed. In outcrossers, by contrast, male- and female-biased flowers and genotypes may have equal fitness and coexist at evolutionary equilibrium. In the absence of strong stabilizing selection on the P:O ratio, selection on this trait will be relaxed, resulting in independence or resource-based trade-offs between male and female investment. To test this prediction, we conducted artificial selection on pollen and ovule production per flower in two sister species with contrasting mating systems. The predominantly self-fertilizing species (Clarkia exilis) consistently exhibited a significant positive r(g) between pollen and ovule production while the outcrossing species (C. unguiculata) exhibited either a trade-off or independence between these traits. Clarkia exilis also exhibited much more highly canalized gender expression than C. unguiculata. Selection on pollen and ovule production resulted in little correlated change in the P:O ratio in the selfing exilis, while dramatic changes in the P:O ratio were observed in unguiculata. To test the common prediction that floral attractiveness should be positively genetically correlated with investment in male function, we examined the response of petal area to selection on pollen and ovule production and found that petal area was not consistently genetically correlated with gender expression in either species. Our results suggest that the joint evolutionary trajectory of primary sexual traits in hermaphroditic species will be affected by their mating systems; this should be taken into account in future theoretical and comparative empirical investigations.

  9. Speciation analysis and leaching behaviors of selected trace elements in spent SCR catalyst.

    PubMed

    Dai, Zejun; Wang, Lele; Tang, Hao; Sun, Zhijun; Liu, Wei; Sun, Yi; Su, Sheng; Hu, Song; Wang, Yi; Xu, Kai; Liu, Liang; Ling, Peng; Xiang, Jun

    2018-09-01

    This study investigated heavy metal chemical speciation and leaching behavior from a board-type spent selective catalytic reduction (SCR) catalyst containing high concentrations of vanadium, chromium, nickel, copper, zinc, and lead. A three-step sequential extraction method, standard toxicity characteristic leaching procedure (TCLP), and leaching characteristic tests have been performed. It was found that the mobility of six heavy metals in the spent SCR catalyst was significantly different. The mobility of the six heavy metals exhibited the following order: Ni > Zn > V > Cr > As > Cu. Meanwhile, TCLP test results revealed relatively high Zn and Cr leaching rate of 83.20% and 10.35%, respectively. It was found that leaching rate was positively correlated with available contents (sum of acid soluble, reducible and oxidizable fractions). Leaching characteristics tests indicated that pH substantially affected the leaching of these heavy metals. In particular, the leaching of Cr, Ni, Cu, and Zn was positively influenced by strong acid, while V and As were easily released in the presence of strong acid and strong alkali (pH < 3 or pH > 11). In terms of kinetics, the leaching of Cr, Ni, Cu, Zn, and As within the spent catalyst was dominated by erosion and dissolution processes, which were rapid reaction processes. V was released in large amounts within 1 h, but its leaching amount sharply decreased with time due to readsorption. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears.

    PubMed

    Liu, Shiping; Lorenzen, Eline D; Fumagalli, Matteo; Li, Bo; Harris, Kelley; Xiong, Zijun; Zhou, Long; Korneliussen, Thorfinn Sand; Somel, Mehmet; Babbitt, Courtney; Wray, Greg; Li, Jianwen; He, Weiming; Wang, Zhuo; Fu, Wenjing; Xiang, Xueyan; Morgan, Claire C; Doherty, Aoife; O'Connell, Mary J; McInerney, James O; Born, Erik W; Dalén, Love; Dietz, Rune; Orlando, Ludovic; Sonne, Christian; Zhang, Guojie; Nielsen, Rasmus; Willerslev, Eske; Wang, Jun

    2014-05-08

    Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. POPULATION GENOMICS REVEAL RECENT SPECIATION AND RAPID EVOLUTIONARY ADAPTATION IN POLAR BEARS

    PubMed Central

    Liu, Shiping; Lorenzen, Eline D.; Fumagalli, Matteo; Li, Bo; Harris, Kelley; Xiong, Zijun; Zhou, Long; Korneliussen, Thorfinn Sand; Somel, Mehmet; Babbitt, Courtney; Wray, Greg; Li, Jianwen; He, Weiming; Wang, Zhuo; Fu, Wenjing; Xiang, Xueyan; Morgan, Claire C.; Doherty, Aoife; O’Connell, Mary J.; McInerney, James O.; Born, Erik W.; Dalén, Love; Dietz, Rune; Orlando, Ludovic; Sonne, Christian; Zhang, Guojie; Nielsen, Rasmus; Willerslev, Eske; Wang, Jun

    2014-01-01

    SUMMARY Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyperlipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479–343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardio-vascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. PMID:24813606

  12. Extrinsic Cation Selectivity of 2D Membranes

    PubMed Central

    2017-01-01

    From a systematic study of the concentration driven diffusion of positive and negative ions across porous 2D membranes of graphene and hexagonal boron nitride (h-BN), we prove their cation selectivity. Using the current–voltage characteristics of graphene and h-BN monolayers separating reservoirs of different salt concentrations, we calculate the reversal potential as a measure of selectivity. We tune the Debye screening length by exchanging the salt concentrations and demonstrate that negative surface charge gives rise to cation selectivity. Surprisingly, h-BN and graphene membranes show similar characteristics, strongly suggesting a common origin of selectivity in aqueous solvents. For the first time, we demonstrate that the cation flux can be increased by using ozone to create additional pores in graphene while maintaining excellent selectivity. We discuss opportunities to exploit our scalable method to use 2D membranes for applications including osmotic power conversion. PMID:28157333

  13. Investigating a memory-based account of negative priming: support for selection-feature mismatch.

    PubMed

    MacDonald, P A; Joordens, S

    2000-08-01

    Using typical and modified negative priming tasks, the selection-feature mismatch account of negative priming was tested. In the modified task, participants performed selections on the basis of a semantic feature (e.g., referent size). This procedure has been shown to enhance negative priming (P. A. MacDonald, S. Joordens, & K. N. Seergobin, 1999). Across 3 experiments, negative priming occurred only when the repeated item mismatched in terms of the feature used as the basis for selections. When the repeated item was congruent on the selection feature across the prime and probe displays, positive priming arose. This pattern of results appeared in both the ignored- and the attended-repetition conditions. Negative priming does not result from previously ignoring an item. These findings strongly support the selection-feature mismatch account of negative priming and refute both the distractor inhibition and the episodic-retrieval explanations.

  14. The interplay of attention economics and computer-aided detection marks in screening mammography

    NASA Astrophysics Data System (ADS)

    Schwartz, Tayler M.; Sridharan, Radhika; Wei, Wei; Lukyanchenko, Olga; Geiser, William; Whitman, Gary J.; Haygood, Tamara Miner

    2016-03-01

    Introduction: According to attention economists, overabundant information leads to decreased attention for individual pieces of information. Computer-aided detection (CAD) alerts radiologists to findings potentially associated with breast cancer but is notorious for creating an abundance of false-positive marks. We suspected that increased CAD marks do not lengthen mammogram interpretation time, as radiologists will selectively disregard these marks when present in larger numbers. We explore the relevance of attention economics in mammography by examining how the number of CAD marks affects interpretation time. Methods: We performed a retrospective review of bilateral digital screening mammograms obtained between January 1, 2011 and February 28, 2014, using only weekend interpretations to decrease distractions and the likelihood of trainee participation. We stratified data according to reader and used ANOVA to assess the relationship between number of CAD marks and interpretation time. Results: Ten radiologists, with median experience after residency of 12.5 years (range 6 to 24,) interpreted 1849 mammograms. When accounting for number of images, Breast Imaging Reporting and Data System category, and breast density, increasing numbers of CAD marks was correlated with longer interpretation time only for the three radiologists with the fewest years of experience (median 7 years.) Conclusion: For the 7 most experienced readers, increasing CAD marks did not lengthen interpretation time. We surmise that as CAD marks increase, the attention given to individual marks decreases. Experienced radiologists may rapidly dismiss larger numbers of CAD marks as false-positive, having learned that devoting extra attention to such marks does not improve clinical detection.

  15. Warning signals are under positive frequency-dependent selection in nature

    PubMed Central

    Chouteau, Mathieu; Arias, Mónica; Joron, Mathieu

    2016-01-01

    Positive frequency-dependent selection (FDS) is a selection regime where the fitness of a phenotype increases with its frequency, and it is thought to underlie important adaptive strategies resting on signaling and communication. However, whether and how positive FDS truly operates in nature remains unknown, which hampers our understanding of signal diversity. Here, we test for positive FDS operating on the warning color patterns of chemically defended butterflies forming multiple coexisting mimicry assemblages in the Amazon. Using malleable prey models placed in localities showing differences in the relative frequencies of warningly colored prey, we demonstrate that the efficiency of a warning signal increases steadily with its local frequency in the natural community, up to a threshold where protection stabilizes. The shape of this relationship is consistent with the direct effect of the local abundance of each warning signal on the corresponding avoidance knowledge of the local predator community. This relationship, which differs from purifying selection acting on each mimetic pattern, indicates that predator knowledge, integrated over the entire community, is saturated only for the most common warning signals. In contrast, among the well-established warning signals present in local prey assemblages, most are incompletely known to local predators and enjoy incomplete protection. This incomplete predator knowledge should generate strong benefits to life history traits that enhance warning efficiency by increasing the effective frequency of prey visible to predators. Strategies such as gregariousness or niche convergence between comimics may therefore readily evolve through their effects on predator knowledge and warning efficiency. PMID:26858416

  16. Development and validation of novel AAV2 random libraries displaying peptides of diverse lengths and at diverse capsid positions.

    PubMed

    Naumer, Matthias; Ying, Ying; Michelfelder, Stefan; Reuter, Antje; Trepel, Martin; Müller, Oliver J; Kleinschmidt, Jürgen A

    2012-05-01

    Libraries based on the insertion of random peptide ligands into the capsid of adeno-associated virus type 2 (AAV2) have been widely used to improve the efficiency and selectivity of the AAV vector system. However, so far only libraries of 7-mer peptide ligands have been inserted at one well-characterized capsid position. Here, we expanded the combinatorial AAV2 display system to a panel of novel AAV libraries, displaying peptides of 5, 7, 12, 19, or 26 amino acids in length at capsid position 588 or displaying 7-mer peptides at position 453, the most prominently exposed region of the viral capsid. Library selections on two unrelated cell types-human coronary artery endothelial cells and rat cardiomyoblasts-revealed the isolation of cell type-characteristic peptides of different lengths mediating strongly improved target-cell transduction, except for the 26-mer peptide ligands. Characterization of vector selectivity by transduction of nontarget cells and comparative gene-transduction analysis using a panel of 44 human tumor cell lines revealed that insertion of different-length peptides allows targeting of distinct cellular receptors for cell entry with similar efficiency, but with different selectivity. The application of such novel AAV2 libraries broadens the spectrum of targetable receptors by capsid-modified AAV vectors and provides the opportunity to choose the best suited targeting ligand for a certain application from a number of different candidates.

  17. Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein.

    PubMed

    Hellberg, M E; Moy, G W; Vacquier, V D

    2000-03-01

    Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (> 25 nonsynonymous substitutions per site per 10(9) years). cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (Dn/Ds > 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism.

  18. Divergent positive selection in rhodopsin from lake and riverine cichlid fishes.

    PubMed

    Schott, Ryan K; Refvik, Shannon P; Hauser, Frances E; López-Fernández, Hernán; Chang, Belinda S W

    2014-05-01

    Studies of cichlid evolution have highlighted the importance of visual pigment genes in the spectacular radiation of the African rift lake cichlids. Recent work, however, has also provided strong evidence for adaptive diversification of riverine cichlids in the Neotropics, which inhabit environments of markedly different spectral properties from the African rift lakes. These ecological and/or biogeographic differences may have imposed divergent selective pressures on the evolution of the cichlid visual system. To test these hypotheses, we investigated the molecular evolution of the dim-light visual pigment, rhodopsin. We sequenced rhodopsin from Neotropical and African riverine cichlids and combined these data with published sequences from African cichlids. We found significant evidence for positive selection using random sites codon models in all cichlid groups, with the highest levels in African lake cichlids. Tests using branch-site and clade models that partitioned the data along ecological (lake, river) and/or biogeographic (African, Neotropical) boundaries found significant evidence of divergent selective pressures among cichlid groups. However, statistical comparisons among these models suggest that ecological, rather than biogeographic, factors may be responsible for divergent selective pressures that have shaped the evolution of the visual system in cichlids. We found that branch-site models did not perform as well as clade models for our data set, in which there was evidence for positive selection in the background. One of our most intriguing results is that the amino acid sites found to be under positive selection in Neotropical and African lake cichlids were largely nonoverlapping, despite falling into the same three functional categories: spectral tuning, retinal uptake/release, and rhodopsin dimerization. Taken together, these results would imply divergent selection across cichlid clades, but targeting similar functions. This study highlights the importance of molecular investigations of ecologically important groups and the flexibility of clade models in explicitly testing ecological hypotheses.

  19. Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study.

    PubMed

    Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

    2015-06-01

    Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and 'relaxed' after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal.

  20. Signature of dislocations and stacking faults of face-centred cubic nanocrystals in coherent X-ray diffraction patterns: a numerical study1

    PubMed Central

    Dupraz, Maxime; Beutier, Guillaume; Rodney, David; Mordehai, Dan; Verdier, Marc

    2015-01-01

    Crystal defects induce strong distortions in diffraction patterns. A single defect alone can yield strong and fine features that are observed in high-resolution diffraction experiments such as coherent X-ray diffraction. The case of face-centred cubic nanocrystals is studied numerically and the signatures of typical defects close to Bragg positions are identified. Crystals of a few tens of nanometres are modelled with realistic atomic potentials and ‘relaxed’ after introduction of well defined defects such as pure screw or edge dislocations, or Frank or prismatic loops. Diffraction patterns calculated in the kinematic approximation reveal various signatures of the defects depending on the Miller indices. They are strongly modified by the dissociation of the dislocations. Selection rules on the Miller indices are provided, to observe the maximum effect of given crystal defects in the initial and relaxed configurations. The effect of several physical and geometrical parameters such as stacking fault energy, crystal shape and defect position are discussed. The method is illustrated on a complex structure resulting from the simulated nanoindentation of a gold nanocrystal. PMID:26089755

  1. Selected nutrients and pesticides in streams of the eastern Iowa basins, 1970-95

    USGS Publications Warehouse

    Schnoebelen, Douglas J.; Becher, Kent D.; Bobier, Matthew W.; Wilton, Thomas

    1999-01-01

     The statistical analysis of the nutrient data typically indicated a strong positive correlation of nitrate with streamflow. Total phosphorus concentrations with streamflow showed greater variability than nitrate, perhaps reflecting the greater potential of transport of phosphorus on sediment rather than in the dissolved phase as with nitrate. Ammonia and ammonia plus organic nitrogen showed no correlation with streamflow or a weak positive correlation. Seasonal variations and the relations of nutrients and pesticides to streamflow generally corresponded with nonpoint‑source loadings, although possible point sources for nutrients were indicated by the data at selected monitoring sites. Statistical trend tests for concentrations and loads were computed for nitrate, ammonia, and total phosphorus. Trend analysis indicated decreases for ammonia and total phosphorus concentrations at several sites and increases for nitrate concentrations at other sites in the study unit.

  2. Genetic parameters for sensory traits in longissimus muscle and their associations with tenderness, marbling score, and intramuscular fat in Angus cattle.

    PubMed

    Mateescu, R G; Garrick, D J; Garmyn, A J; VanOverbeke, D L; Mafi, G G; Reecy, J M

    2015-01-01

    The objective of this study was to estimate heritabilities for sensory traits and genetic correlations among sensory traits and with marbling score (MS), Warner-Bratzler shear force (WBSF), and intramuscular fat content (IMFC). Samples of LM from 2,285 Angus cattle were obtained and fabricated into steaks for laboratory analysis and 1,720 steaks were analyzed by a trained sensory panel. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multitrait animal model. Estimates of heritability for MS, IMFC, WBSF, tenderness, juiciness, and connective tissue traits were 0.67, 0.38, 0.19, 0.18, 0.06, and 0.25, respectively. The genetic correlations of MS with tenderness, juiciness, and connective tissue were estimated to be 0.57 ± 0.14, 1.00 ± 0.17, and 0.49 ± 0.13, all positive and strong. Estimated genetic correlations of IMFC with tenderness, juiciness, and connective tissue were 0.56 ± 0.16, 1.00 ± 0.21, and 0.50 ± 0.15, respectively. The genetic correlations of WBSF with tenderness, juiciness, and connective tissue were all favorable and estimated to be -0.99 ± 0.08, -0.33 ± 0.30 and -0.99 ± 0.07, respectively. Strong and positive genetic correlations were estimated between tenderness and juiciness (0.54 ± 0.28) and between connective tissue and juiciness (0.58 ± 0.26). In general, genetic correlations were large and favorable, which indicated that strong relationships exist and similar gene and gene networks may control MS, IMFC, and juiciness or WBSF, panel tenderness, and connective tissue. The results from this study confirm that MS currently used in selection breeding programs has positive genetic correlations with tenderness and juiciness and, therefore, is an effective indicator trait for the improvement of tenderness and juiciness in beef. This study also indicated that a more objective measure, particularly WBSF, a trait not easy to improve through phenotypic selection, is an excellent candidate trait for genomic selection aimed at improving eating satisfaction.

  3. Through Sex, Nature Is Telling Us Something Important.

    PubMed

    Kondrashov, Alexey S

    2018-05-01

    Theoretically, a variety of mechanisms can make amphimixis advantageous due to reshuffling of offspring genotypes. Recently, it has been shown experimentally that some of these mechanisms can indeed work in artificial populations. However, we still do not know which of them, if any, are relevant in nature, and the available indirect estimates seem to suggest that neither negative nor positive selection in natural populations is strong enough to provide evolutionary protection for obligate amphimixis. Thus, progress in understanding the evolution of amphimixis will depend on direct measurements of the strength of natural selection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Multivariate sexual selection on male tegmina in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae).

    PubMed

    Ower, G D; Hunt, J; Sakaluk, S K

    2017-02-01

    Although the strength and form of sexual selection on song in male crickets have been studied extensively, few studies have examined selection on the morphological structures that underlie variation in males' song, particularly in wild populations. Geometric morphometric techniques were used to measure sexual selection on the shape, size and symmetry of both top and bottom tegmina in wild populations of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. The size of the tegmina negatively covaried with song dominant frequency and positively covaried with song pulse duration. Sexual selection was more intense on the bottom tegmen, conceivably because it interacts more freely with the subtegminal airspace, which may play a role in song amplification. An expanded coastal/subcostal region was one of the phenotypes strongly favoured by disruptive selection on the bottom tegmen, an adaptation that may form a more effective seal with the thorax to prevent noise cancellation. Directional selection also favoured increased symmetry in tegminal shape. Assuming more symmetrical males are better able to buffer against developmental noise, the song produced by these males may make them more attractive to females. Despite the strong stabilizing selection documented previously on the dominant frequency of the song, stabilizing selection on the resonator that regulates dominant frequency was surprisingly absent. Nonetheless, wing morphology had an important influence on song structure and appears to be subject to significant linear and nonlinear sexual selection through female mate choice. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  5. A model of directional selection applied to the evolution of drug resistance in HIV-1.

    PubMed

    Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

    2007-04-01

    Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

  6. Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens.

    PubMed

    Liljavirta, J; Ekman, A; Knight, J S; Pernthaner, A; Iivanainen, A; Niku, M

    2013-09-01

    Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression. The mutational profile in the fetuses is similar to postnatal and immunized calves, with targeting of complementarity-determining region (CDR) over framework region (FR), preference of replacement over silent mutations in CDRs but not in FRs, and targeting of the AID hotspot motif RGYW/WRCY. Statistical analysis indicates negative selection on FRs and positive selection on CDRs. Our results suggest that AID-mediated somatic hypermutation and selection take place in bovine fetuses, implying a role for AID in the diversification of the primary antibody repertoire in the absence of exogenous antigens.

  7. Developmental constraints shape the evolution of the nematode mid-developmental transition.

    PubMed

    Zalts, Harel; Yanai, Itai

    2017-03-27

    Evolutionary theory assumes that genetic variation is uniform and gradual in nature, yet morphological and gene expression studies have revealed that different life-stages exhibit distinct levels of cross-species conservation. In particular, a stage in mid-embryogenesis is highly conserved across species of the same phylum, suggesting that this stage is subject to developmental constraints, either by increased purifying selection or by a strong mutational bias. An alternative explanation, however, holds that the same 'hourglass' pattern of variation may result from increased positive selection at the earlier and later stages of development. To distinguish between these scenarios, we examined gene expression variation in a population of the nematode Caenorhabditis elegans using an experimental design that eliminated the influence of positive selection. By measuring gene expression for all genes throughout development in 20 strains, we found that variations were highly uneven throughout development, with a significant depletion during mid-embryogenesis. In particular, the family of homeodomain transcription factors, whose expression generally coincides with mid-embryogenesis, evolved under high constraint. Our data further show that genes responsible for the integration of germ layers during morphogenesis are the most constrained class of genes. Together, these results provide strong evidence for developmental constraints as the mechanism underlying the hourglass model of animal evolution. Understanding the pattern and mechanism of developmental constraints provides a framework to understand how evolutionary processes have interacted with embryogenesis and led to the diversity of animal life on Earth.

  8. Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion

    PubMed Central

    Solomon, Gregory; Gersch, William; Yoon, Young-Ho; Collura, Randall; Ruvolo, Maryellen; Barrett, J. Carl; Woods, C. Geoffrey; Walsh, Christopher A

    2004-01-01

    Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size. PMID:15045028

  9. How can second-stage management prevent perineal trauma? Critical review.

    PubMed Central

    Flynn, P.; Franiek, J.; Janssen, P.; Hannah, W. J.; Klein, M. C.

    1997-01-01

    OBJECTIVE: To learn which factors influencing perineal integrity were modifiable by physicians and pregnant women. DATA SOURCES: Medical, nursing, and midwifery literature was searched mainly for randomized controlled trials. STUDY SELECTION: We chose articles on perineal trauma pattern, sexual dysfunction or satisfaction, urinary incontinence, and pelvic floor function. We identified 80 papers and studied 16 in detail. SYNTHESIS: Five factors affected perineal integrity: episiotomy, third-trimester perineal massage, mother's position in second-stage labour, method of pushing, and administration of epidural analgesia. Episiotomy does not improve perineal outcomes when used routinely. Third-trimester perineal massage was discussed only in inadequate studies. Studies comparing position in birth chairs and recumbent versus upright positions were inadequate for making firm recommendations. Studies of methods of pushing and use of epidural analgesia were limited and uncontrolled; no recommendations were possible. CONCLUSION: Only limiting episiotomy can be strongly recommended. In the absence of strong data to the contrary, women should be encouraged to engage in perineal massage if they wish and to adopt the birth positions of their choice. Caretakers should be aware of the possibility of interfering with placental function when women hold their breath for a long time when pushing. PMID:9626426

  10. Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.

    PubMed

    Akmatov, Manas K; Röber, Nadja; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Greiser, Halina; Günther, Kathrin; Kaaks, Rudolf; Kemmling, Yvonne; Krone, Bastian; Linseisen, Jakob; Meisinger, Christa; Moebus, Susanne; Obi, Nadia; Guzman, Carlos A; Conrad, Karsten; Pessler, Frank

    2017-06-06

    We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models. Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ 2 , p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed. The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.

  11. Aromatic hydroxylation by cytochrome P450: model calculations of mechanism and substituent effects.

    PubMed

    Bathelt, Christine M; Ridder, Lars; Mulholland, Adrian J; Harvey, Jeremy N

    2003-12-10

    The mechanism and selectivity of aromatic hydroxylation by cytochrome P450 enzymes is explored using new B3LYP density functional theory computations. The calculations, using a realistic porphyrin model system, show that rate-determining addition of compound I to an aromatic carbon atom proceeds via a transition state with partial radical and cationic character. Reactivity is shown to depend strongly on ring substituents, with both electron-withdrawing and -donating groups strongly decreasing the addition barrier in the para position, and it is shown that the calculated barrier heights can be reproduced by a new dual-parameter equation based on radical and cationic Hammett sigma parameters.

  12. Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

    PubMed Central

    2008-01-01

    Polyguanidinium oxanorbornene (PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents. PMID:18850741

  13. Positive selection and ancient duplications in the evolution of class B floral homeotic genes of orchids and grasses

    PubMed Central

    Mondragón-Palomino, Mariana; Hiese, Luisa; Härter, Andrea; Koch, Marcus A; Theißen, Günter

    2009-01-01

    Background Positive selection is recognized as the prevalence of nonsynonymous over synonymous substitutions in a gene. Models of the functional evolution of duplicated genes consider neofunctionalization as key to the retention of paralogues. For instance, duplicate transcription factors are specifically retained in plant and animal genomes and both positive selection and transcriptional divergence appear to have played a role in their diversification. However, the relative impact of these two factors has not been systematically evaluated. Class B MADS-box genes, comprising DEF-like and GLO-like genes, encode developmental transcription factors essential for establishment of perianth and male organ identity in the flowers of angiosperms. Here, we contrast the role of positive selection and the known divergence in expression patterns of genes encoding class B-like MADS-box transcription factors from monocots, with emphasis on the family Orchidaceae and the order Poales. Although in the monocots these two groups are highly diverse and have a strongly canalized floral morphology, there is no information on the role of positive selection in the evolution of their distinctive flower morphologies. Published research shows that in Poales, class B-like genes are expressed in stamens and in lodicules, the perianth organs whose identity might also be specified by class B-like genes, like the identity of the inner tepals of their lily-like relatives. In orchids, however, the number and pattern of expression of class B-like genes have greatly diverged. Results The DEF-like genes from Orchidaceae form four well-supported, ancient clades of orthologues. In contrast, orchid GLO-like genes form a single clade of ancient orthologues and recent paralogues. DEF-like genes from orchid clade 2 (OMADS3-like genes) are under less stringent purifying selection than the other orchid DEF-like and GLO-like genes. In comparison with orchids, purifying selection was less stringent in DEF-like and GLO-like genes from Poales. Most importantly, positive selection took place before the major organ reduction and losses in the floral axis that eventually yielded the zygomorphic grass floret. Conclusion In DEF-like genes of Poales, positive selection on the region mediating interactions with other proteins or DNA could have triggered the evolution of the regulatory mechanisms behind the development of grass-specific reproductive structures. Orchidaceae show a different trend, where gene duplication and transcriptional divergence appear to have played a major role in the canalization and modularization of perianth development. PMID:19383167

  14. Geometric mean IELT and premature ejaculation: appropriate statistics to avoid overestimation of treatment efficacy.

    PubMed

    Waldinger, Marcel D; Zwinderman, Aeilko H; Olivier, Berend; Schweitzer, Dave H

    2008-02-01

    The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results. To explain the rightful use of geometrical mean IELT values and the fold increase of the geometric mean IELT because of the positively skewed IELT distribution. Linking theoretical arguments to the outcome of several selective serotonin reuptake inhibitor and modern antidepressant study results. Geometric mean IELT and fold increase of geometrical mean IELT. Log-transforming each separate IELT measurement of each individual man is the basis for the calculation of the geometric mean IELT. A drug-induced positively skewed IELT distribution necessitates the calculation of the geometric mean IELTs at baseline and during drug treatment. In a positively skewed IELT distribution, the use of the "arithmetic" mean IELT risks an overestimation of the drug-induced ejaculation delay as the mean IELT is always higher than the geometric mean IELT. Strong ejaculation-delaying drugs give rise to a strong positively skewed IELT distribution, whereas weak ejaculation-delaying drugs give rise to (much) less skewed IELT distributions. Ejaculation delay is expressed in fold increase of the geometric mean IELT. Drug-induced ejaculatory performance discloses a positively skewed IELT distribution, requiring the use of the geometric mean IELT and the fold increase of the geometric mean IELT.

  15. Weak orientation and direction selectivity in lateral geniculate nucleus representing central vision in the gray squirrel Sciurus carolinensis

    PubMed Central

    Zaltsman, Julia B.; Heimel, J. Alexander

    2015-01-01

    Classic studies of lateral geniculate nucleus (LGN) and visual cortex (V1) in carnivores and primates have found that a majority of neurons in LGN exhibit a center-surround organization, while V1 neurons exhibit strong orientation selectivity and, in many species, direction selectivity. Recent work in the mouse and the monkey has discovered previously unknown classes of orientation- and direction-selective neurons in LGN. Furthermore, some recent studies in the mouse report that many LGN cells exhibit pronounced orientation biases that are of comparable strength to the subthreshold inputs to V1 neurons. These results raise the possibility that, in rodents, orientation biases of individual LGN cells make a substantial contribution to cortical orientation selectivity. Alternatively, the size and contribution of orientation- or direction-selective channels from LGN to V1 may vary across mammals. To address this question, we examined orientation and direction selectivity in LGN and V1 neurons of a highly visual diurnal rodent: the gray squirrel. In the representation of central vision, only a few LGN neurons exhibited strong orientation or direction selectivity. Across the population, LGN neurons showed weak orientation biases and were much less selective for orientation compared with V1 neurons. Although direction selectivity was weak overall, LGN layers 3abc, which contain neurons that express calbindin, exhibited elevated direction selectivity index values compared with LGN layers 1 and 2. These results suggest that, for central visual fields, the contribution of orientation- and direction-selective channels from the LGN to V1 is small in the squirrel. As in other mammals, this small contribution is elevated in the calbindin-positive layers of the LGN PMID:25717157

  16. Compositional pressure and translational selection determine codon usage in the extremely GC-poor unicellular eukaryote Entamoeba histolytica.

    PubMed

    Romero, H; Zavala, A; Musto, H

    2000-01-25

    It is widely accepted that the compositional pressure is the only factor shaping codon usage in unicellular species displaying extremely biased genomic compositions. This seems to be the case in the prokaryotes Mycoplasma capricolum, Rickettsia prowasekii and Borrelia burgdorferi (GC-poor), and in Micrococcus luteus (GC-rich). However, in the GC-poor unicellular eukaryotes Dictyostelium discoideum and Plasmodium falciparum, there is evidence that selection, acting at the level of translation, influences codon choices. This is a twofold intriguing finding, since (1) the genomic GC levels of the above mentioned eukaryotes are lower than the GC% of any studied bacteria, and (2) bacteria usually have larger effective population sizes than eukaryotes, and hence natural selection is expected to overcome more efficiently the randomizing effects of genetic drift among prokaryotes than among eukaryotes. In order to gain a new insight about this problem, we analysed the patterns of codon preferences of the nuclear genes of Entamoeba histolytica, a unicellular eukaryote characterised by an extremely AT-rich genome (GC = 25%). The overall codon usage is strongly biased towards A and T in the third codon positions, and among the presumed highly expressed sequences, there is an increased relative usage of a subset of codons, many of which are C-ending. Since an increase in C in third codon positions is 'against' the compositional bias, we conclude that codon usage in E. histolytica, as happens in D. discoideum and P. falciparum, is the result of an equilibrium between compositional pressure and selection. These findings raise the question of why strongly compositionally biased eukaryotic cells may be more sensitive to the (presumed) slight differences among synonymous codons than compositionally biased bacteria.

  17. Sensation seeking and visual selective attention in adults with HIV/AIDS.

    PubMed

    Hardy, David J; Castellon, Steven A; Hinkin, Charles H; Levine, Andrew J; Lam, Mona N

    2008-11-01

    The association between sensation seeking and visual selective attention was examined in 31 adults with the Human Immunodeficiency Virus (HIV). Sensation seeking was measured with Zuckerman's Sensation Seeking Scale Form V (SSS-V). Selective attention was assessed with a perceptual span task, where a target letter-character must be identified in a quickly presented array of nontarget letter-characters. As predicted, sensation seeking was strongly associated (R(2) = .229) with perceptual span performance in the array size 12 condition, where selective attention demands were greatest, but not in the easier conditions. The Disinhibition, Boredom Susceptibility, and Experience Seeking subscales of the SSS-V were associated with span performance. It is argued that personality factors such as sensation seeking may play a significant role in selective attention and related cognitive abilities in HIV positive adults. Furthermore, sensation seeking differences might explain certain inconsistencies in the HIV neuropsychology literature.

  18. Whole-genome resequencing reveals signatures of selection and timing of duck domestication.

    PubMed

    Zhang, Zebin; Jia, Yaxiong; Almeida, Pedro; Mank, Judith E; van Tuinen, Marcel; Wang, Qiong; Jiang, Zhihua; Chen, Yu; Zhan, Kai; Hou, Shuisheng; Zhou, Zhengkui; Li, Huifang; Yang, Fangxi; He, Yong; Ning, Zhonghua; Yang, Ning; Qu, Lujiang

    2018-04-01

    The genetic basis of animal domestication remains poorly understood, and systems with substantial phenotypic differences between wild and domestic populations are useful for elucidating the genetic basis of adaptation to new environments as well as the genetic basis of rapid phenotypic change. Here, we sequenced the whole genome of 78 individual ducks, from two wild and seven domesticated populations, with an average sequencing depth of 6.42X per individual. Our population and demographic analyses indicate a complex history of domestication, with early selection for separate meat and egg lineages. Genomic comparison of wild to domesticated populations suggests that genes that affect brain and neuronal development have undergone strong positive selection during domestication. Our FST analysis also indicates that the duck white plumage is the result of selection at the melanogenesis-associated transcription factor locus. Our results advance the understanding of animal domestication and selection for complex phenotypic traits.

  19. Soybean (Glycine max) expansin gene superfamily origins: segmental and tandem duplication events followed by divergent selection among subfamilies

    PubMed Central

    2014-01-01

    Background Expansins are plant cell wall loosening proteins that are involved in cell enlargement and a variety of other developmental processes. The expansin superfamily contains four subfamilies; namely, α-expansin (EXPA), β-expansin (EXPB), expansin-like A (EXLA), and expansin-like B (EXLB). Although the genome sequencing of soybeans is complete, our knowledge about the pattern of expansion and evolutionary history of soybean expansin genes remains limited. Results A total of 75 expansin genes were identified in the soybean genome, and grouped into four subfamilies based on their phylogenetic relationships. Structural analysis revealed that the expansin genes are conserved in each subfamily, but are divergent among subfamilies. Furthermore, in soybean and Arabidopsis, the expansin gene family has been mainly expanded through tandem and segmental duplications; however, in rice, segmental duplication appears to be the dominant process that generates this superfamily. The transcriptome atlas revealed notable differential expression in either transcript abundance or expression patterns under normal growth conditions. This finding was consistent with the differential distribution of the cis-elements in the promoter region, and indicated wide functional divergence in this superfamily. Moreover, some critical amino acids that contribute to functional divergence and positive selection were detected. Finally, site model and branch-site model analysis of positive selection indicated that the soybean expansin gene superfamily is under strong positive selection, and that divergent selection constraints might have influenced the evolution of the four subfamilies. Conclusion This study demonstrated that the soybean expansin gene superfamily has expanded through tandem and segmental duplication. Differential expression indicated wide functional divergence in this superfamily. Furthermore, positive selection analysis revealed that divergent selection constraints might have influenced the evolution of the four subfamilies. In conclusion, the results of this study contribute novel detailed information about the molecular evolution of the expansin gene superfamily in soybean. PMID:24720629

  20. Adaptive evolution of osmoregulatory-related genes provides insight into salinity adaptation in Chinese mitten crab, Eriocheir sinensis.

    PubMed

    Wang, Zhengfei; Bai, Yuze; Zhang, Daizhen; Tang, Boping

    2018-06-01

    Osmoregulation is an important mechanism by which euryhaline crustaceans regulate osmotic and ionic concentrations. The Chinese mitten crab (Eriocheir sinensis) is a strong osmoregulating animal model among crustacean species, as it can maintain its hemolymph composition and survives well in either seawater or freshwater. Osmoregulation by E. sinensis during physiological adaptation has been studied extensively. However, the genetic basis of osmoregulation in E. sinensis for acclimating to changing salinities remains unclear. The current study investigated five genes involved in E. sinensis osmoregulation and compared them with a representative marine crab Portunus trituberculatus to test whether adaptive evolution has occurred changing salinity conditions. The results showed that carbonic anhydrase (CA), cytochrome P450 4C (CYP4C), glutamate dehydrogenase (GDH), and the Na + /H + exchanger (NHE) have undergone positive selection (i.e., directional selection) in E. sinensis. Thus, the positive selection in CA and NHE suggests that E. sinensis has enhanced capacity for maintaining systemic acid-base balance and ion regulation. GDH and CYP4C also demonstrated positive selection in E. sinensis, suggesting that E. sinensis might have acquired an enhanced capacity to metabolize glutamate and synthesize ecdysteroids in response to a change in osmotic concentration. The present study provides new insight into the molecular genetic basis of salinity adaption in E. sinensis.

  1. Adaptive Patterns of Mitogenome Evolution Are Associated with the Loss of Shell Scutes in Turtles.

    PubMed

    Escalona, Tibisay; Weadick, Cameron J; Antunes, Agostinho

    2017-10-01

    The mitochondrial genome encodes several protein components of the oxidative phosphorylation (OXPHOS) pathway and is critical for aerobic respiration. These proteins have evolved adaptively in many taxa, but linking molecular-level patterns with higher-level attributes (e.g., morphology, physiology) remains a challenge. Turtles are a promising system for exploring mitochondrial genome evolution as different species face distinct respiratory challenges and employ multiple strategies for ensuring efficient respiration. One prominent adaptation to a highly aquatic lifestyle in turtles is the secondary loss of keratenized shell scutes (i.e., soft-shells), which is associated with enhanced swimming ability and, in some species, cutaneous respiration. We used codon models to examine patterns of selection on mitochondrial protein-coding genes along the three turtle lineages that independently evolved soft-shells. We found strong evidence for positive selection along the branches leading to the pig-nosed turtle (Carettochelys insculpta) and the softshells clade (Trionychidae), but only weak evidence for the leatherback (Dermochelys coriacea) branch. Positively selected sites were found to be particularly prevalent in OXPHOS Complex I proteins, especially subunit ND2, along both positively selected lineages, consistent with convergent adaptive evolution. Structural analysis showed that many of the identified sites are within key regions or near residues involved in proton transport, indicating that positive selection may have precipitated substantial changes in mitochondrial function. Overall, our study provides evidence that physiological challenges associated with adaptation to a highly aquatic lifestyle have shaped the evolution of the turtle mitochondrial genome in a lineage-specific manner. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Cryogenic filter wheel design for an infrared instrument

    NASA Astrophysics Data System (ADS)

    Azcue, Joaquín.; Villanueva, Carlos; Sánchez, Antonio; Polo, Cristina; Reina, Manuel; Carretero, Angel; Torres, Josefina; Ramos, Gonzalo; Gonzalez, Luis M.; Sabau, Maria D.; Najarro, Francisco; Pintado, Jesús M.

    2014-09-01

    In the last two decades, Spain has built up a strong IR community which has successfully contributed to space instruments, reaching Co-PI level in the SPICA mission (Space Infrared Telescope for Cosmology and Astrophysics). Under the SPICA mission, INTA, focused on the SAFARI instrument requirements but highly adaptable to other missions has designed a cryogenic low dissipation filter wheel with six positions, taking as starting point the past experience of the team with the OSIRIS instrument (ROSETTA mission) filter wheels and adapting the design to work at cryogenic temperatures. One of the main goals of the mechanism is to use as much as possible commercial components and test them at cryogenic temperature. This paper is focused on the design of the filter wheel, including the material selection for each of the main components of the mechanism, the design of elastic mount for the filter assembly, a positioner device designed to provide positional accuracy and repeatability to the filter, allowing the locking of the position without dissipation. In order to know the position of the wheel on every moment a position sensor based on a Hall sensor was developed. A series of cryogenic tests have been performed in order to validate the material configuration selected, the ball bearing lubrication and the selection of the motor. A stepper motor characterization campaign was performed including heat dissipation measurements. The result is a six position filter wheel highly adaptable to different configurations and motors using commercial components. The mechanism was successfully tested at INTA facilities at 20K at breadboard level.

  3. Sexual selection gradients change over time in a simultaneous hermaphrodite

    PubMed Central

    Hoffer, Jeroen NA; Mariën, Janine; Ellers, Jacintha; Koene, Joris M

    2017-01-01

    Sexual selection is generally predicted to act more strongly on males than on females. The Darwin-Bateman paradigm predicts that this should also hold for hermaphrodites. However, measuring this strength of selection is less straightforward when both sexual functions are performed throughout the organism’s lifetime. Besides, quantifications of sexual selection are usually done during a short time window, while many animals store sperm and are long-lived. To explore whether the chosen time frame affects estimated measures of sexual selection, we recorded mating success and reproductive success over time, using a simultaneous hermaphrodite. Our results show that male sexual selection gradients are consistently positive. However, an individual’s female mating success seems to negatively affect its own male reproductive success, an effect that only becomes visible several weeks into the experiment, highlighting that the time frame is crucial for the quantification and interpretation of sexual selection measures, an insight that applies to any iteroparous mating system. DOI: http://dx.doi.org/10.7554/eLife.25139.001 PMID:28613158

  4. Allergenicity of mare's milk in children with cow's milk allergy.

    PubMed

    Businco, L; Giampietro, P G; Lucenti, P; Lucaroni, F; Pini, C; Di Felice, G; Iacovacci, P; Curadi, C; Orlandi, M

    2000-05-01

    Cow's milk allergy is a common disease of infancy and early childhood. If the baby is not breast-fed, a substitute for cow's milk formula is necessary. The aim of this study was to investigate, in vitro and in vivo, the allergenicity of mare's milk in a population of selected children with severe IgE-mediated cow's milk allergy. Twenty-five children (17 male and 8 female) aged 19 to 72 months (median age 34 months) with IgE-mediated cow's milk allergy were selected for this study. All the children underwent skin prick tests with cow's milk and mare's milk and double-blind placebo-controlled oral food challenge (DBPCOFC) with fresh cow's milk, fresh mare's milk, and, as placebo, a soy formula (Isomil, Abbott, Campoverde, Italy). We performed immunoblotting of cow's and mare's milk developed with IgE from allergic children. All the children showed strong positive skin test responses to cow's milk (4+); 2 children had positive skin test responses to mare's milk (2+). All children had positive DBPCOFCs to cow's milk; one child had a positive DBPCOFC to mare's milk. No children reacted to the placebo (Isomil). In the cow's milk, some proteins are able to strongly react with human IgE; when the sera are tested with mare's milk, the bands corresponding to the same proteins are recognized by a lower percentage of sera. These data suggest that mare's milk can be regarded as a good substitute of cow's milk in most children with severe IgE-mediated cow's milk allergy. It would be prudent, however, to confirm its tolerability by a supervised titrated oral challenge test.

  5. Genome-wide evidence for divergent selection between populations of a major agricultural pathogen.

    PubMed

    Hartmann, Fanny E; McDonald, Bruce A; Croll, Daniel

    2018-06-01

    The genetic and environmental homogeneity in agricultural ecosystems is thought to impose strong and uniform selection pressures. However, the impact of this selection on plant pathogen genomes remains largely unknown. We aimed to identify the proportion of the genome and the specific gene functions under positive selection in populations of the fungal wheat pathogen Zymoseptoria tritici. First, we performed genome scans in four field populations that were sampled from different continents and on distinct wheat cultivars to test which genomic regions are under recent selection. Based on extended haplotype homozygosity and composite likelihood ratio tests, we identified 384 and 81 selective sweeps affecting 4% and 0.5% of the 35 Mb core genome, respectively. We found differences both in the number and the position of selective sweeps across the genome between populations. Using a XtX-based outlier detection approach, we identified 51 extremely divergent genomic regions between the allopatric populations, suggesting that divergent selection led to locally adapted pathogen populations. We performed an outlier detection analysis between two sympatric populations infecting two different wheat cultivars to identify evidence for host-driven selection. Selective sweep regions harboured genes that are likely to play a role in successfully establishing host infections. We also identified secondary metabolite gene clusters and an enrichment in genes encoding transporter and protein localization functions. The latter gene functions mediate responses to environmental stress, including interactions with the host. The distinct gene functions under selection indicate that both local host genotypes and abiotic factors contributed to local adaptation. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  6. Selective Targeting of Cancer Stem Cells by 2-Aminodihydroquinoline Analogs.

    PubMed

    Park, Heejoo; Yu, Yeongji; Kim, Hyejin; Lee, Eun; Lee, Hani; Jeon, Raok; Kim, Woo-Young

    2017-04-01

    Many aminodihydroquinoline compounds have been studied to determine their cytotoxicity to cancer cells. However, anti-cancer stem cells (CSCs) activity of aminodihydroquinoline has not been tested in spite that CSC is believed to do an important roles in chemotherapy resistance and recurrence. The CSC selective targeting activities of 10 recently synthesized 2-aminodihydroquinoline analogs were examined on CSCs and bulk culture of a glioblastoma cell line. A diethylaminopropyl substituted aminodihydroquinoline, 5h, showed a strong anti-CSC effect and general cytotoxicity. However, a benzyl substituted aminodihydroquinoline, 5i, displayed the most effective anti-CSC effect, with no or small significant cytotoxic effect in bulk culture conditions. While 5h temporarily enhanced CSC marker-positive cells and eventually suppressed the CSC population, which is similar to other cytotoxic anticancer reagents reported, 5i selectively eliminated CSC marker-positive cells based on fluorescence activated cell sorter (FACS) analysis. 5h also temporarily activated some genes associated with signaling required for CSC, while 5i selectively suppressed these genes supporting that the differential effects are resulted from different molecular responses. In addition, the selective CSC effect is also found against a colon cancer cell line. Collectively, we suggest that these two novel aminodihydroquinoline compounds possess novel anti-CSC effects in colon and brain tumor derived cell lines probably through independent pathways.

  7. Selecting habitat to survive: the impact of road density on survival in a large carnivore.

    PubMed

    Basille, Mathieu; Van Moorter, Bram; Herfindal, Ivar; Martin, Jodie; Linnell, John D C; Odden, John; Andersen, Reidar; Gaillard, Jean-Michel

    2013-01-01

    Habitat selection studies generally assume that animals select habitat and food resources at multiple scales to maximise their fitness. However, animals sometimes prefer habitats of apparently low quality, especially when considering the costs associated with spatially heterogeneous human disturbance. We used spatial variation in human disturbance, and its consequences on lynx survival, a direct fitness component, to test the Hierarchical Habitat Selection hypothesis from a population of Eurasian lynx Lynx lynx in southern Norway. Data from 46 lynx monitored with telemetry indicated that a high proportion of forest strongly reduced the risk of mortality from legal hunting at the home range scale, while increasing road density strongly increased such risk at the finer scale within the home range. We found hierarchical effects of the impact of human disturbance, with a higher road density at a large scale reinforcing its negative impact at a fine scale. Conversely, we demonstrated that lynx shifted their habitat selection to avoid areas with the highest road densities within their home ranges, thus supporting a compensatory mechanism at fine scale enabling lynx to mitigate the impact of large-scale disturbance. Human impact, positively associated with high road accessibility, was thus a stronger driver of lynx space use at a finer scale, with home range characteristics nevertheless constraining habitat selection. Our study demonstrates the truly hierarchical nature of habitat selection, which aims at maximising fitness by selecting against limiting factors at multiple spatial scales, and indicates that scale-specific heterogeneity of the environment is driving individual spatial behaviour, by means of trade-offs across spatial scales.

  8. Positive selection in the SLC11A1 gene in the family Equidae.

    PubMed

    Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan; Orlando, Ludovic; Horin, Petr

    2016-05-01

    Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed.

  9. The Puzzle of HIV Neutral and Selective Evolution.

    PubMed

    Leitner, Thomas

    2018-06-01

    HIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that. HIV evolution is also a clear example of strong positive selection, that is, mutants have a survival advantage. How do these facts come together?

  10. On causal roles and selected effects: our genome is mostly junk.

    PubMed

    Doolittle, W Ford; Brunet, Tyler D P

    2017-12-05

    The idea that much of our genome is irrelevant to fitness-is not the product of positive natural selection at the organismal level-remains viable. Claims to the contrary, and specifically that the notion of "junk DNA" should be abandoned, are based on conflating meanings of the word "function". Recent estimates suggest that perhaps 90% of our DNA, though biochemically active, does not contribute to fitness in any sequence-dependent way, and possibly in no way at all. Comparisons to vertebrates with much larger and smaller genomes (the lungfish and the pufferfish) strongly align with such a conclusion, as they have done for the last half-century.

  11. A catalog of selected compact radio sources for the construction of an extragalactic radio/optical reference frame (Argue et al. 1984): Documentation for the machine-readable version

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This document describes the machine readable version of the Selected Compact Radio Source Catalog as it is currently being distributed from the international network of astronomical data centers. It is intended to enable users to read and process the computerized catalog. The catalog contains 233 strong, compact extragalactic radio sources having identified optical counterparts. The machine version contains the same data as the published catalog and includes source identifications, equatorial positions at J2000.0 and their mean errors, object classifications, visual magnitudes, redshift, 5-GHz flux densities, and comments.

  12. Influence of ionospheric disturbances onto long-baseline relative positioning in kinematic mode

    NASA Astrophysics Data System (ADS)

    Wezka, Kinga; Herrera, Ivan; Cokrlic, Marija; Galas, Roman

    2013-04-01

    Ionospheric disturbances are fast and random variabilities in the ionosphere and they are difficult to detect and model. Some strong disturbances can cause, among others, interruption of GNSS signal or even lead to loss of signal lock. These phenomena are especially harmful for kinematic real-time applications, where the system availability is one of the most important parameters influencing positioning reliability. Our investigations were conducted using long time series of GNSS observations gathered at high latitude, where ionospheric disturbances more frequently occur. Selected processing strategy was used to monitor ionospheric signatures in time series of the coordinates. Quality of the data of input and of the processing results were examined and described by a set of proposed parameters. Variations in the coordinates were compared with available information about the state of ionosphere derived from Neustrelitz TEC Model (NTCM) and with the time series of raw observations. Some selected parameters were also calculated with the "iono-tools" module of the TUB-NavSolutions software developed by the Precise Navigation and Positioning Group at Technische Universitaet Berlin. The paper presents very first results of evaluation of the robustness of positioning algorithms with respect to ionospheric anomalies using the NTCM model and our calculated ionospheric parameters.

  13. Massive expansion and differential evolution of small heat shock proteins with wheat (Triticum aestivum L.) polyploidization.

    PubMed

    Wang, Xiaoming; Wang, Ruochen; Ma, Chuang; Shi, Xue; Liu, Zhenshan; Wang, Zhonghua; Sun, Qixin; Cao, Jun; Xu, Shengbao

    2017-05-31

    Wheat (Triticum aestivum), one of the world's most important crops, is facing unprecedented challenges due to global warming. To evaluate the gene resources for heat adaptation in hexaploid wheat, small heat shock proteins (sHSPs), the key plant heat protection genes, were comprehensively analysed in wheat and related species. We found that the sHSPs of hexaploid wheat were massively expanded in A and B subgenomes with intrachromosomal duplications during polyploidization. These expanded sHSPs were under similar purifying selection and kept the expressional patterns with the original copies. Generally, a strong purifying selection acted on the α-crystallin domain (ACD) and theoretically constrain conserved function. Meanwhile, weaker purifying selection and strong positive selection acted on the N-terminal region, which conferred sHSP flexibility, allowing adjustments to a wider range of substrates in response to genomic and environmental changes. Notably, in CI, CV, ER, MI and MII subfamilies, gene duplications, expression variations and functional divergence occurred before wheat polyploidization. Our results indicate the massive expansion of active sHSPs in hexaploid wheat may also provide more raw materials for evolving functional novelties and generating genetic diversity to face future global climate changes, and highlight the expansion of stress response genes with wheat polyploidization.

  14. A thrifty variant in CREBRF strongly influences body mass index in Samoans.

    PubMed

    Minster, Ryan L; Hawley, Nicola L; Su, Chi-Ting; Sun, Guangyun; Kershaw, Erin E; Cheng, Hong; Buhule, Olive D; Lin, Jerome; Reupena, Muagututi'a Sefuiva; Viali, Satupa'itea; Tuitele, John; Naseri, Take; Urban, Zsolt; Deka, Ranjan; Weeks, Daniel E; McGarvey, Stephen T

    2016-09-01

    Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10(-14)), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10(-9)). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10(-20)). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36-1.45 kg/m(2) per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a 'thrifty' variant hypothesis as a factor in human obesity.

  15. Symptom assessment in early psychosis: the use of well-established rating scales in clinical high-risk and recent-onset populations.

    PubMed

    Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K; Fisher, Melissa; Mathalon, Daniel H; Vinogradov, Sophia; Loewy, Rachel L

    2014-12-30

    Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical-high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms; for the CHR group only, we included the Scale of Prodromal Symptoms. For investigators selecting symptom measures in intervention or longitudinal studies, we also examined the relationship of symptom scales with psychosocial functioning. In both samples, symptom subscales in the same domain, across measures, were moderately to highly intercorrelated. Within all measures, positive symptoms were not correlated with negative symptoms, but disorganized symptoms overlapped with both positive and negative symptoms. Functioning was significantly related to negative and disorganized, but not positive, symptoms in both samples on most measures. Findings suggest strong overlap in symptom severity ratings among the most common scales. In recent-onset samples, each has strengths and weaknesses. In CHR samples, they appear to add little information above and beyond the SOPS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Working Memory Replay Prioritizes Weakly Attended Events.

    PubMed

    Jafarpour, Anna; Penny, Will; Barnes, Gareth; Knight, Robert T; Duzel, Emrah

    2017-01-01

    One view of working memory posits that maintaining a series of events requires their sequential and equal mnemonic replay. Another view is that the content of working memory maintenance is prioritized by attention. We decoded the dynamics for retaining a sequence of items using magnetoencephalography, wherein participants encoded sequences of three stimuli depicting a face, a manufactured object, or a natural item and maintained them in working memory for 5000 ms. Memory for sequence position and stimulus details were probed at the end of the maintenance period. Decoding of brain activity revealed that one of the three stimuli dominated maintenance independent of its sequence position or category; and memory was enhanced for the selectively replayed stimulus. Analysis of event-related responses during the encoding of the sequence showed that the selectively replayed stimuli were determined by the degree of attention at encoding. The selectively replayed stimuli had the weakest initial encoding indexed by weaker visual attention signals at encoding. These findings do not rule out sequential mnemonic replay but reveal that attention influences the content of working memory maintenance by prioritizing replay of weakly encoded events. We propose that the prioritization of weakly encoded stimuli protects them from interference during the maintenance period, whereas the more strongly encoded stimuli can be retrieved from long-term memory at the end of the delay period.

  17. Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

    PubMed

    Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

    2018-04-01

    The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

  18. Geochemical conditions and the occurrence of selected trace elements in groundwater basins used for public drinking-water supply, Desert and Basin and Range hydrogeologic provinces, 2006-11: California GAMA Priority Basin Project

    USGS Publications Warehouse

    Wright, Michael T.; Fram, Miranda S.; Belitz, Kenneth

    2015-01-01

    Concentrations of strontium, which exists primarily in a cationic form (Sr2+), were not significantly correlated with either groundwater age or pH. Strontium concentrations showed a strong positive correlation with total dissolved solids (TDS). Dissolved constituents, such as Sr, that interact with mineral surfaces through outer-sphere complexation become increasingly soluble with increasing TDS concentrations of groundwater. Boron concentrations also showed a significant positive correlation with TDS, indicating the B may interact to a large degree with mineral surfaces through outer-sphere complexation.

  19. Psychosocial Factors Influencing Smokeless Tobacco Use by Teenage Military Dependents

    DTIC Science & Technology

    1994-01-01

    age and grade Demographics both show strong bivariate relationships with the outcome MALE-male gender measures, we selected to use only one of these...a positive sign indicating a direct relation- no impact for either gender . Attitude and other tobacco influ- ship and a negative sign an inverse...by both genders . nlficant. However, if the interval includes one but is highly For both genders , the strongest explanatory variable for trial skewed

  20. Evolutionary games on cycles with strong selection

    NASA Astrophysics Data System (ADS)

    Altrock, P. M.; Traulsen, A.; Nowak, M. A.

    2017-02-01

    Evolutionary games on graphs describe how strategic interactions and population structure determine evolutionary success, quantified by the probability that a single mutant takes over a population. Graph structures, compared to the well-mixed case, can act as amplifiers or suppressors of selection by increasing or decreasing the fixation probability of a beneficial mutant. Properties of the associated mean fixation times can be more intricate, especially when selection is strong. The intuition is that fixation of a beneficial mutant happens fast in a dominance game, that fixation takes very long in a coexistence game, and that strong selection eliminates demographic noise. Here we show that these intuitions can be misleading in structured populations. We analyze mean fixation times on the cycle graph under strong frequency-dependent selection for two different microscopic evolutionary update rules (death-birth and birth-death). We establish exact analytical results for fixation times under strong selection and show that there are coexistence games in which fixation occurs in time polynomial in population size. Depending on the underlying game, we observe inherence of demographic noise even under strong selection if the process is driven by random death before selection for birth of an offspring (death-birth update). In contrast, if selection for an offspring occurs before random removal (birth-death update), then strong selection can remove demographic noise almost entirely.

  1. Do nonexercisers also share the positive exerciser stereotype?: An elicitation and comparison of beliefs about exercisers.

    PubMed

    Rodgers, Wendy M; Hall, Craig R; Wilson, Philip M; Berry, Tanya R

    2009-02-01

    The purpose of this research was to examine whether exercisers and nonexercisers are rated similarly on a variety of characteristics by a sample of randomly selected regular exercisers, nonexercisers who intend to exercise, and nonexercisers with no intention to exercise. Previous research by Martin Ginis et al. (2003) has demonstrated an exerciser stereotype that advantages exercisers. It is unknown, however, the extent to which an exerciser stereotype is shared by nonexercisers, particularly nonintenders. Following an item-generation procedure, a sample of 470 (n=218 men; n=252 women) people selected using random digit dialing responded to a questionnaire assessing the extent to which they agreed that exercisers and nonexercisers possessed 24 characteristics, such as "happy," "fit," "fat," and "lazy." The results strongly support a positive exerciser bias, with exercisers rated more favorably on 22 of the 24 items. The degree of bias was equivalent in all groups of respondents. Examination of the demographic characteristics revealed no differences among the three groups on age, work status, or child-care responsibilities, suggesting that there is a pervasive positive exerciser bias.

  2. Event-related potential evidence for separable automatic and controlled retrieval processes in proactive interference.

    PubMed

    Bergström, Zara M; O'Connor, Richard J; Li, Martin K-H; Simons, Jon S

    2012-05-21

    Interference between competing memories is a major source of retrieval failure, yet, surprisingly little is known about how competitive memory activation arises in the brain. One possibility is that interference during episodic retrieval might be produced by relatively automatic conceptual priming mechanisms that are independent of strategic retrieval processes. Such priming-driven interference might occur when the competing memories have strong pre-existing associations to the retrieval cue. We used ERPs to measure the neural dynamics of retrieval competition, and investigated whether the ERP correlates of interference were affected by varying task demands for selective retrieval. Participants encoded cue words that were presented either two or four times, paired either with the same or different strongly associated words across repetitions. In a subsequent test, participants either selectively recalled each cue's most recent associate, or simply judged how many times a cue had been presented, without requiring selective recall. Interference effects on test performance were only seen in the recall task. In contrast, ERPs during test revealed an early posterior positivity for high interference items that was present in both retrieval tasks. This early ERP effect likely reflects a conceptual priming-related N400 reduction when many associations to a cue were pre-activated. A later parietal positivity resembling the ERP correlate of conscious recollection was found only in the recall task. The results suggest that early effects of proactive interference are relatively automatic and independent of intentional retrieval processes, consistent with suggestions that interference can arise through conceptual priming. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Molecular adaptation and resilience of the insect’s nuclear receptor USP

    PubMed Central

    2012-01-01

    Background The maintenance of biological systems requires plasticity and robustness. The function of the ecdysone receptor, a heterodimer composed of the nuclear receptors ECR (NR1H1) and USP (NR2B4), was maintained in insects despite a dramatic divergence that occurred during the emergence of Mecopterida. This receptor is therefore a good model to study the evolution of plasticity. We tested the hypothesis that selection has shaped the Ligand-Binding Domain (LBD) of USP during evolution of Mecopterida. Results We isolated usp and cox1 in several species of Drosophilidae, Tenebrionidae and Blattaria and estimated non-synonymous/synonymous rate ratios using maximum-likelihood methods and codon-based substitution models. Although the usp sequences were mainly under negative selection, we detected relaxation at residues located on the surface of the LBD within Mecopterida families. Using branch-site models, we also detected changes in selective constraints along three successive branches of the Mecopterida evolution. Residues located at the bottom of the ligand-binding pocket (LBP) underwent strong positive selection during the emergence of Mecopterida. This change is correlated with the acquisition of a large LBP filled by phospholipids that probably allowed the stabilisation of the new Mecopterida structure. Later, when the two subgroups of Mecopterida (Amphiesmenoptera: Lepidoptera, Trichoptera; Antliophora: Diptera, Mecoptera, Siphonaptera) diverged, the same positions became under purifying selection. Similarly, several positions of the heterodimerisation interface experienced positive selection during the emergence of Mecopterida, rapidly followed by a phase of constrained evolution. An enlargement of the heterodimerisation surface is specific for Mecopterida and was associated with a reinforcement of the obligatory partnership between ECR and USP, at the expense of homodimerisation. Conclusions In order to explain the episodic mode of evolution of USP, we propose a model in which the molecular adaptation of this protein is seen as a process of resilience for the maintenance of the ecdysone receptor functionality. PMID:23039844

  4. MR Enterography of the Ileoanal Pouch: Descriptive Radiologic Analysis With Endoscopic and Pathologic Correlation.

    PubMed

    Sahi, Kamaldeep Singh; Lee, Karen S; Moss, Alan; Yee, Eric; Allard, Felicia; Brook, Alexander; Mortele, Koenraad J

    2015-11-01

    The purpose of this study was to describe the MR enterography (MRE) appearance of inflammation of the ileoanal pouch after ileal pouch-anal anastomosis (IPAA) surgery and to correlate it with pouch endoscopic and histopathologic findings. All MRE studies performed between October 1, 2007, and September 30, 2013, for patients who had previously undergone IPAA (n = 54) were retrieved. After review of medical records, the patients who underwent MRE, pouch endoscopy, and biopsy within 90 days (14 men, 14 women; mean age, 42.2 years; range, 24-67 years) were selected for inclusion in the study. Two blinded MRI radiologists in consensus retrospectively evaluated MRE studies for multiple MRI features. Two MRI scores were then calculated: an active and a composite inflammation score. A gastroenterologist retrospectively reviewed the pouch endoscopic images, and a pathologist reviewed the slides; both of these investigators were blinded. Both MRI scores were correlated with the pouch endoscopic and histopathologic findings. The composite MRI score had strong positive correlation with the endoscopic score (r = 0.61; p = 0.0005) but weak positive correlation with the histopathologic score (r = 0.31; p = 0.10, not statistically significant). The active inflammation MRI score had moderate positive correlation with the endoscopic score (r = 0.57; p = 0.0017) and weak positive correlation with the histopathologic score (r = 0.20; p = 0.31, not statistically significant). An MRI score ≥ 4 indicated the best results, with sensitivity of 86%, specificity of 79%, positive predictive value of 80%, negative predictive value of 85%, and accuracy of 82% for pouch inflammation. A positive likelihood ratio of 4.00 and negative likelihood ratio of 0.18 were obtained. In patients who have undergone IPAA surgery, the MRE findings strongly correlate with the pouch endoscopic findings with high sensitivity and positive predictive value for pouch inflammation. Therefore, MRE is a useful noninvasive test performed without ionizing radiation that can be used to evaluate patients with clinical symptoms and possibly alleviate the need for endoscopy in a select patient population.

  5. Positive selection drives the evolution of a major histocompatibility complex gene in an endangered Mexican salamander species complex.

    PubMed

    Tracy, Karen E; Kiemnec-Tyburczy, Karen M; DeWoody, J Andrew; Parra-Olea, Gabriela; Zamudio, Kelly R

    2015-06-01

    Immune gene evolution can be critical to species survival in the face of infectious disease. In particular, polymorphism in the genes of the major histocompatibility complex (MHC) helps vertebrates combat novel and diverse pathogens by increasing the number of pathogen-derived proteins that can initiate the host's acquired immune response. In this study, we used a combination of presumably adaptive and neutral markers to investigate MHC evolution in populations of five salamander species within the Ambystoma velasci complex, a group consisting of 15 recently diverged species, several of which are endangered. We isolated 31 unique MHC class II β alleles from 75 total individuals from five species in this complex. MHC heterozygosity was significantly lower than expected for all five species, and we found no clear relationship between number of MHC alleles and species range, life history, or level of heterozygosity. We inferred a phylogeny representing the evolutionary history of Ambystoma MHC, with which we found signatures of positive selection on the overall gene, putative peptide-binding residues, and allelic lineages. We identified several instances of trans-species polymorphism, a hallmark of balancing selection observed in other groups of closely related species. In contrast, we did not detect comparable allelic diversity or signatures of selection on neutral loci. Additionally, we identified 17 supertypes among the 44 unique Ambystoma alleles, indicating that these sequences may encode functionally distinct MHC variants. We therefore have strong evidence that positive selection is a major evolutionary force driving patterns of MHC polymorphism in this recently radiated species complex.

  6. Dengue virus type 1 clade replacement in recurring homotypic outbreaks

    PubMed Central

    2013-01-01

    Background Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control. Results We used a set of viral envelope (E) gene to reconstruct the phylogeny of DENV-1 isolated between the periods of 1987–2011 in Malaysia. Phylogenetic analysis of DENV-1 E gene revealed that genotype I virus clade replacements were associated with the cyclical pattern of major DENV-1 outbreaks in Malaysia. A total of 9 non-conservative amino acid substitutions in the DENV-1 E gene consensus were identified; 4 in domain I, 3 in domain II and 2 in domain III. Selection pressure analyses did not reveal any positively selected codon site within the full length E gene sequences (1485 nt, 495 codons). A total of 183 (mean dN/dS = 0.0413) negatively selected sites were found within the Malaysian isolates; neither positive nor negative selection was noted for the remaining 312 codons. All the viruses were cross-neutralized by the respective patient sera suggesting no strong support for immunological advantage of any of the amino acid substitutions. Conclusion DENV-1 clade replacement is associated with recurrences of major DENV-1 outbreaks in Malaysia. Our findings are consistent with those of other studies that the DENV-1 clade replacement is a stochastic event independent of positive selection. PMID:24073945

  7. Queens and Workers Contribute Differently to Adaptive Evolution in Bumble Bees and Honey Bees.

    PubMed

    Harpur, Brock A; Dey, Alivia; Albert, Jennifer R; Patel, Sani; Hines, Heather M; Hasselmann, Martin; Packer, Laurence; Zayed, Amro

    2017-09-01

    Eusociality represents a major transition in evolution and is typified by cooperative brood care and reproductive division of labor between generations. In bees, this division of labor allows queens and workers to phenotypically specialize. Worker traits associated with helping are thought to be crucial to the fitness of a eusocial lineage, and recent studies of honey bees (genus Apis) have found that adaptively evolving genes often have worker-biased expression patterns. It is unclear however if worker-biased genes are disproportionately acted on by strong positive selection in all eusocial insects. We undertook a comparative population genomics study of bumble bees (Bombus) and honey bees to quantify natural selection on queen- and worker-biased genes across two levels of social complexity. Despite sharing a common eusocial ancestor, genes, and gene groups with the highest levels of positive selection were often unique within each genus, indicating that life history and the environment, but not sociality per se, drives patterns of adaptive molecular evolution. We uncovered differences in the contribution of queen- and worker-biased genes to adaptive evolution in bumble bees versus honey bees. Unlike honey bees, where worker-biased genes are enriched for signs of adaptive evolution, genes experiencing positive selection in bumble bees were predominately expressed by reproductive foundresses during the initial solitary-founding stage of colonies. Our study suggests that solitary founding is a major selective pressure and that the loss of queen totipotency may cause a change in the architecture of selective pressures upon the social insect genome. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Duplication and population dynamics shape historic patterns of selection and genetic variation at the major histocompatibility complex in rodents

    PubMed Central

    Winternitz, Jamie C; Wares, John P

    2013-01-01

    Genetic variation at the major histocompatibility complex (MHC) is vitally important for wildlife populations to respond to pathogen threats. As natural populations can fluctuate greatly in size, a key issue concerns how population cycles and bottlenecks that could reduce genetic diversity will influence MHC genes. Using 454 sequencing, we characterized genetic diversity at the DRB Class II locus in montane voles (Microtus montanus), a North American rodent that regularly undergoes high-amplitude fluctuations in population size. We tested for evidence of historic balancing selection, recombination, and gene duplication to identify mechanisms maintaining allelic diversity. Counter to our expectations, we found strong evidence of purifying selection acting on the DRB locus in montane voles. We speculate that the interplay between population fluctuations and gene duplication might be responsible for the weak evidence of historic balancing selection and strong evidence of purifying selection detected. To further explore this idea, we conducted a phylogenetically controlled comparative analysis across 16 rodent species with varying demographic histories and MHC duplication events (based on the maximum number of alleles detected per individual). On the basis of phylogenetic generalized linear model-averaging, we found evidence that the estimated number of duplicated loci was positively related to allelic diversity and, surprisingly, to the strength of purifying selection at the DRB locus. Our analyses also revealed that species that had undergone population bottlenecks had lower allelic richness than stable species. This study highlights the need to consider demographic history and genetic structure alongside patterns of natural selection to understand resulting patterns of genetic variation at the MHC. PMID:23789067

  9. Immune Selection In Vitro Reveals Human Immunodeficiency Virus Type 1 Nef Sequence Motifs Important for Its Immune Evasion Function In Vivo

    PubMed Central

    Lee, Patricia; Ng, Hwee L.; Yang, Otto O.

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) Nef downregulates major histocompatibility complex class I (MHC-I), impairing the clearance of infected cells by CD8+ cytotoxic T lymphocytes (CTLs). While sequence motifs mediating this function have been determined by in vitro mutagenesis studies of laboratory-adapted HIV-1 molecular clones, it is unclear whether the highly variable Nef sequences of primary isolates in vivo rely on the same sequence motifs. To address this issue, nef quasispecies from nine chronically HIV-1-infected persons were examined for sequence evolution and altered MHC-I downregulatory function under Gag-specific CTL immune pressure in vitro. This selection resulted in decreased nef diversity and strong purifying selection. Site-by-site analysis identified 13 codons undergoing purifying selection and 1 undergoing positive selection. Of the former, only 6 have been reported to have roles in Nef function, including 4 associated with MHC-I downregulation. Functional testing of naturally occurring in vivo polymorphisms at the 7 sites with no previously known functional role revealed 3 mutations (A84D, Y135F, and G140R) that ablated MHC-I downregulation and 3 (N52A, S169I, and V180E) that partially impaired MHC-I downregulation. Globally, the CTL pressure in vitro selected functional Nef from the in vivo quasispecies mixtures that predominately lacked MHC-I downregulatory function at the baseline. Overall, these data demonstrate that CTL pressure exerts a strong purifying selective pressure for MHC-I downregulation and identifies novel functional motifs present in Nef sequences in vivo. PMID:22553319

  10. A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data

    PubMed Central

    DeGiorgio, Michael; Lohmueller, Kirk E.; Nielsen, Rasmus

    2014-01-01

    While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates. PMID:25144706

  11. A model-based approach for identifying signatures of ancient balancing selection in genetic data.

    PubMed

    DeGiorgio, Michael; Lohmueller, Kirk E; Nielsen, Rasmus

    2014-08-01

    While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.

  12. Frequency-dependent selection can lead to evolution of high mutation rates.

    PubMed

    Rosenbloom, Daniel I S; Allen, Benjamin

    2014-05-01

    Theoretical and experimental studies have shown that high mutation rates can be advantageous, especially in novel or fluctuating environments. Here we examine how frequency-dependent competition may lead to fluctuations in trait frequencies that exert upward selective pressure on mutation rates. We use a mathematical model to show that cyclical trait dynamics generated by "rock-paper-scissors" competition can cause the mutation rate in a population to converge to a high evolutionarily stable mutation rate, reflecting a trade-off between generating novelty and reproducing past success. Introducing recombination lowers the evolutionarily stable mutation rate but allows stable coexistence between mutation rates above and below the evolutionarily stable rate. Even considering strong mutational load and ignoring the costs of faithful replication, evolution favors positive mutation rates if the selective advantage of prevailing in competition exceeds the ratio of recombining to nonrecombining offspring. We discuss a number of genomic mechanisms that may meet our theoretical requirements for the adaptive evolution of mutation. Overall, our results suggest that local mutation rates may be higher on genes influencing cyclical competition and that global mutation rates in asexual species may be higher in populations subject to strong cyclical competition.

  13. Synchronisation hubs in the visual cortex may arise from strong rhythmic inhibition during gamma oscillations.

    PubMed

    Folias, Stefanos E; Yu, Shan; Snyder, Abigail; Nikolić, Danko; Rubin, Jonathan E

    2013-09-01

    Neurons in the visual cortex exhibit heterogeneity in feature selectivity and the tendency to generate action potentials synchronously with other nearby neurons. By examining visual responses from cat area 17 we found that, during gamma oscillations, there was a positive correlation between each unit's sharpness of orientation tuning, strength of oscillations, and propensity towards synchronisation with other units. Using a computational model, we demonstrated that heterogeneity in the strength of rhythmic inhibitory inputs can account for the correlations between these three properties. Neurons subject to strong inhibition tend to oscillate strongly in response to both optimal and suboptimal stimuli and synchronise promiscuously with other neurons, even if they have different orientation preferences. Moreover, these strongly inhibited neurons can exhibit sharp orientation selectivity provided that the inhibition they receive is broadly tuned relative to their excitatory inputs. These results predict that the strength and orientation tuning of synaptic inhibition are heterogeneous across area 17 neurons, which could have important implications for these neurons' sensory processing capabilities. Furthermore, although our experimental recordings were conducted in the visual cortex, our model and simulation results can apply more generally to any brain region with analogous neuron types in which heterogeneity in the strength of rhythmic inhibition can arise during gamma oscillations. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Natural Selection and Genetic Diversity in the Butterfly Heliconius melpomene.

    PubMed

    Martin, Simon H; Möst, Markus; Palmer, William J; Salazar, Camilo; McMillan, W Owen; Jiggins, Francis M; Jiggins, Chris D

    2016-05-01

    A combination of selective and neutral evolutionary forces shape patterns of genetic diversity in nature. Among the insects, most previous analyses of the roles of drift and selection in shaping variation across the genome have focused on the genus Drosophila A more complete understanding of these forces will come from analyzing other taxa that differ in population demography and other aspects of biology. We have analyzed diversity and signatures of selection in the neotropical Heliconius butterflies using resequenced genomes from 58 wild-caught individuals of Heliconius melpomene and another 21 resequenced genomes representing 11 related species. By comparing intraspecific diversity and interspecific divergence, we estimate that 31% of amino acid substitutions between Heliconius species are adaptive. Diversity at putatively neutral sites is negatively correlated with the local density of coding sites as well as nonsynonymous substitutions and positively correlated with recombination rate, indicating widespread linked selection. This process also manifests in significantly reduced diversity on longer chromosomes, consistent with lower recombination rates. Although hitchhiking around beneficial nonsynonymous mutations has significantly shaped genetic variation in H. melpomene, evidence for strong selective sweeps is limited overall. We did however identify two regions where distinct haplotypes have swept in different populations, leading to increased population differentiation. On the whole, our study suggests that positive selection is less pervasive in these butterflies as compared to fruit flies, a fact that curiously results in very similar levels of neutral diversity in these very different insects. Copyright © 2016 by the Genetics Society of America.

  15. Biphalin analogs containing β(3)-homo-amino acids at the 4,4' positions: Synthesis and opioid activity profiles.

    PubMed

    Frączak, Oliwia; Lasota, Anika; Kosson, Piotr; Leśniak, Anna; Muchowska, Adriana; Lipkowski, Andrzej W; Olma, Aleksandra

    2015-04-01

    Biphalin, a synthetic opioid octapeptide with a palindromic sequence has high analgesic activity. Biphalin displays a strong affinity for μ and δ-opioid receptors, and a significant to κ-receptor. The paper reports the synthesis of novel analogs of biphalin containing β(3)-homo-amino acid residues at the 4,4' positions and a hydrazine or 1,2-phenylenediamine linker. The potency and selectivity of the peptides were evaluated by a competitive receptor-binding assay in rat brain homogenate using [(3)H]DAMGO (a μ ligand) and [(3)H]DELT (a δ ligand). Analogs with β(3)-h-p-NO2Phe in positions 4 and 4' are the most active compounds. Selectivity depends on the degree of freedom between the two pharmacophore moieties. Analogs with a hydrazine linker show noticeable binding selectivity to μ receptors (IC50(μ)=0.72nM; IC50(δ)=4.66nM), while the peptides with a 1,2-phenylenediamine linker show slight δ selectivity (IC50(μ)=10.97nM; IC50(δ)=1.99nM). Tyr-d-Ala-Gly-β(3)-h-p-NO2PheNHNH-β(3)-h-p-NO2Phe (1) and (Tyr-d-Ala-Gly-β(3)-h-p-NO2PheNH)2 (2) produced greater antinociceptive effect compared to morphine after i.t. administration. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Full-genome dengue virus sequencing in mosquito saliva shows lack of convergent positive selection during transmission by Aedes aegypti

    PubMed Central

    Cao-Lormeau, Van-Mai; Lambrechts, Louis

    2017-01-01

    Abstract Like other pathogens with high mutation and replication rates, within-host dengue virus (DENV) populations evolve during infection of their main mosquito vector, Aedes aegypti. Within-host DENV evolution during transmission provides opportunities for adaptation and emergence of novel virus variants. Recent studies of DENV genetic diversity failed to detect convergent evolution of adaptive mutations in mosquito tissues such as midgut and salivary glands, suggesting that convergent positive selection is not a major driver of within-host DENV evolution in the vector. However, it is unknown whether this conclusion extends to the transmitted viral subpopulation because it is technically difficult to sequence DENV genomes in mosquito saliva. Here, we achieved DENV full-genome sequencing by pooling saliva samples collected non-sacrificially from 49 to 163 individual Ae. aegypti mosquitoes previously infected with one of two DENV-1 genotypes. We compared the transmitted viral subpopulations found in the pooled saliva samples collected in time series with the input viral population present in the infectious blood meal. In all pooled saliva samples examined, the full-genome consensus sequence of the input viral population was unchanged. Although the pooling strategy prevents analysis of individual saliva samples, our results demonstrate the lack of strong convergent positive selection during a single round of DENV transmission by Ae. aegypti. This finding reinforces the idea that genetic drift and purifying selection are the dominant evolutionary forces shaping within-host DENV genetic diversity during transmission by mosquitoes. PMID:29497564

  17. The application of positive psychology in the practice of education.

    PubMed

    Pluskota, Anna

    2014-01-01

    The purpose of the study is to present the possibility of the application in the field of education this highly interesting and promising trend in the psychology which is the positive psychology. For this reason the origins as well as an outline of the interest scope of this relatively recent, dating back only over 10 years, trend are shown. A crucial question has become in this context the examination of the relationship between the positive psychology and the education, particularly regarding the potential linked to the prospect of the so called strong points". The founding fathers as well as the supporters of the positive psychology try to propagate it in the therapy and in the fields of organization and education. In the following text some selected concepts of the positive psychology and the corresponding examples of their practical use in the form of the so called positive prevention and intervention programs in the domain of education are described.

  18. Affective processing in positive schizotypy: Loose control of social-emotional information.

    PubMed

    Papousek, Ilona; Weiss, Elisabeth M; Mosbacher, Jochen A; Reiser, Eva M; Schulter, Günter; Fink, Andreas

    2014-10-30

    Behavioral studies suggested heightened impact of emotionally laden perceptual input in schizophrenia spectrum disorders, in particular in patients with prominent positive symptoms. De-coupling of prefrontal and posterior cortices during stimulus processing, which is related to loosening of control of the prefrontal cortex over incoming affectively laden information, may underlie this abnormality. Pre-selected groups of individuals with low versus high positive schizotypy (lower and upper quartile of a large screening sample) were tested. During exposure to auditory displays of strong emotions (anger, sadness, cheerfulness), individuals with elevated levels of positive schizotypal symptoms showed lesser prefrontal-posterior coupling (EEG coherence) than their symptom-free counterparts (right hemisphere). This applied to negative emotions in particular and was most pronounced during confrontation with anger. The findings indicate a link between positive symptoms and a heightened impact particularly of threatening emotionally laden stimuli which might lead to exacerbation of positive symptoms and inappropriate behavior in interpersonal situations. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Attitudes of Iranian infertile couples toward surrogacy.

    PubMed

    Kian, Ensiyeh Mohebbi; Riazi, Hedieh; Bashirian, Saeid

    2014-01-01

    Surrogacy arrangements are multifaceted in nature, involving multiple controversial aspects and engaging ethical, moral, psychological and social issues. Successful treatment in reproductive medicine is strongly based on the mutual agreement of both partners, especially in Iran where men often make the final decision for health-related problems of this nature. The aim of the following study is to assess the attitudes of Iranian infertile couples toward surrogacy. This descriptive study was conducted at the infertility clinic of Hamadan university of medical sciences, Iran. The study sample consisted of 150 infertile couples selected using a systematic randomized method. Data collection was based on responses to a questionnaire consisting of 22 questions. P <0.05 were considered to be statistically significant. While 33.3% of men and 43.3% of women surveyed insisted on not using surrogacy, the overall attitudes toward surrogacy were positive (53.3% of women and 54.6% of men surveyed). Although, there was not a significant difference between the overall positive attitudes of infertile women and men toward surrogacy, the general attitude toward using this method is not strongly positive. Therefore, further efforts are required to increase the acceptability of surrogacy among infertile couples.

  20. Molecular population genetics of the melanic plumage polymorphism in Arctic skuas (Stercorarius parasiticus): evidence for divergent selection on plumage colour.

    PubMed

    Janssen, Kirstin; Mundy, Nicholas I

    2013-09-01

    The Arctic skua (Stercorarius parasiticus) is a classic example of an avian plumage polymorphism, with variation in melanin-based ventral plumage coloration defining pale, intermediate and dark morphs in adults of both sexes. However, despite several decades of field research, there is an incomplete understanding of how the polymorphism in ventral plumage colour is maintained and the selective forces involved. Here, we investigate selection on a locus (MC1R) that is strongly associated with plumage colour variation in Arctic skuas using patterns of nucleotide variation and comparison to neutral loci (nuclear introns and mtDNA). We find that three linked nonsynonymous mutations in MC1R, including the single mutation described previously, are associated with plumage colour in the Arctic skua. The position of nonsynonymous mutations on a MC1R haplotype network implies that divergent selection drove the initial evolution of the colour morphs. Comparisons of F(ST)s of MC1R vs. nuclear introns among five skua populations differing in proportion of dark morphs along an approximate north-south cline reveal a signature of divergent selection on MC1R. In contrast, we find limited evidence for balancing selection on MC1R within populations, although the power is low. Our results provide strong evidence for both past and ongoing selection on MC1R, and, by implication, plumage colour in Arctic skuas. The results suggest that a fruitful avenue for future ecological studies will be analysis of selection on morphs in colonies at the extremes along the morph ratio cline. © 2013 John Wiley & Sons Ltd.

  1. Amphetamine Challenge: A Marker of Brain Function that Mediates Risk for Drug and Alcohol Abuse

    DTIC Science & Technology

    2008-05-01

    drugs. We record the effects of the drug on their mood , and select a group of people who experience strong, positive feelings from the drug...in other research projects), we identified the task parameters that would reliably elicit in young adults (i.e., in the age range we planned to test...manuscript, University of Minnesota, Minneapolis, MN. Tellegen, A. (1985). Structure of mood and personality and their relevance to assessing anxiety

  2. Importance of positioning for microbial evolution

    PubMed Central

    Kim, Wook; Racimo, Fernando; Schluter, Jonas; Levy, Stuart B.; Foster, Kevin R.

    2014-01-01

    Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring. Here we show that spontaneous mutants repeatedly arise, push their way to the surface, and dominate colonies of the bacterium Pseudomonas fluorescens Pf0-1. Microscopy and modeling suggests that these mutants use secretions to expand and push themselves up to the growth surface to gain the best access to oxygen. Physically mixing the cells in the colony, or introducing space limitations, largely removes the mutant’s advantage, showing a key link between fitness and the ability of the cells to position themselves in the colony. We next follow over 500 independent adaptation events and show that all occur through mutation of a single repressor of secretions, RsmE, but that the mutants differ in competitiveness. This process allows us to map the genetic basis of their adaptation at high molecular resolution and we show how evolutionary competitiveness is explained by the specific effects of each mutation. By combining population level and molecular analyses, we demonstrate how living in dense microbial communities can generate strong natural selection to reach the growing edge. PMID:24715732

  3. Rapid molecular evolution of human bocavirus revealed by Bayesian coalescent inference.

    PubMed

    Zehender, Gianguglielmo; De Maddalena, Chiara; Canuti, Marta; Zappa, Alessandra; Amendola, Antonella; Lai, Alessia; Galli, Massimo; Tanzi, Elisabetta

    2010-03-01

    Human bocavirus (HBoV) is a linear single-stranded DNA virus belonging to the Parvoviridae family that has recently been isolated from the upper respiratory tract of children with acute respiratory infection. All of the strains observed so far segregate into two genotypes (1 and 2) with a low level of polymorphism. Given the recent description of the infection and the lack of epidemiological and molecular data, we estimated the virus's rates of molecular evolution and population dynamics. A dataset of forty-nine dated VP2 sequences, including also eight new isolates obtained from pharyngeal swabs of Italian patients with acute respiratory tract infections, was submitted to phylogenetic analysis. The model parameters, evolutionary rates and population dynamics were co-estimated using a Bayesian Markov Chain Monte Carlo approach, and site-specific positive and negative selection was also investigated. Recombination was investigated by seven different methods and one suspected recombinant strain was excluded from further analysis. The estimated mean evolutionary rate of HBoV was 8.6x10(-4)subs/site/year, and that of the 1st+2nd codon positions was more than 15 times less than that of the 3rd codon position. Viral population dynamics analysis revealed that the two known genotypes diverged recently (mean tMRCA: 24 years), and that the epidemic due to HBoV genotype 2 grew exponentially at a rate of 1.01year(-1). Selection analysis of the partial VP2 showed that 8.5% of sites were under significant negative pressure and the absence of positive selection. Our results show that, like other parvoviruses, HBoV is characterised by a rapid evolution. The low level of polymorphism is probably due to a relatively recent divergence between the circulating genotypes and strong purifying selection acting on viral antigens.

  4. Evolution of major histocompatibility complex class I and class II genes in the brown bear

    PubMed Central

    2012-01-01

    Background Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia. PMID:23031405

  5. Evolution of major histocompatibility complex class I and class II genes in the brown bear.

    PubMed

    Kuduk, Katarzyna; Babik, Wiesław; Bojarska, Katarzyna; Sliwińska, Ewa B; Kindberg, Jonas; Taberlet, Pierre; Swenson, Jon E; Radwan, Jacek

    2012-10-02

    Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

  6. Monitoring of vegetation condition using the NDVI/ENSO anomalies in Central Asia and their relationships with ONI (very strong) phases

    NASA Astrophysics Data System (ADS)

    Aralova, Dildora; Toderich, Kristina; Jarihani, Ben; Gafurov, Dilshod; Gismatulina, Liliya

    2016-10-01

    An investigation of temporal dynamics of El Niño-Southern Oscillation (ENSO) and spatial patterns of dryness/wetness period over arid and semi-arid zones of Central Asia and their relationship with Normalized Difference Vegetation Index (NDVI) values (1982-2011) have explored in this article. For identifying periodical oscillations and their relationship with NDVI values have selected El Nino 3.4 index and thirty years of new generation bi-weekly NDVI 3g acquired by the Advanced Very High Resolution Radiometer (AVHRR) satellites time-series data. Based on identification ONI (Oceanic Nino Index) is a very strong El Nino (warm) anomalies observed during 1982-1983, 1997-1998 and very strong La Nino (cool) period events have observed 1988-1989 years. For correlation these two factors and seeking positive and negative trends it has extracted from NDVI time series data as "low productivity period" following years: 1982-1983, 1997 -1998; and as "high productivity period" following years: 1988 -1989. Linear regression observed warm events as moderate phase period selected between moderate El Nino (ME) and NDVI with following periods:1986-1987; 1987-1988; 1991-1992; 2002-2003; 2009-2010; and moderate La Niña (ML) periods and NDVI (1998-1999; 1999-2000; 2007-2008) which has investigated a spatial patterns of wetness conditions. The results indicated that an inverse relationship between very strong El Nino and NDVI, decreased vegetation response with larger positive ONI value; and direct relationship between very strong La Niña and NDVI, increased vegetation response with smaller negative ONI value. Results assumed that significant impact of these anomalies influenced on vegetation productivity. These results will be a beneficial for efficient rangeland/grassland management and to propose drought periods for assessment and reducing quantity of flocks' due to a lack of fodder biomass for surviving livestock flocks on upcoming years in rangelands. Also results demonstrate that a non-anthropogenic drivers of variability effected to land surface vegetation signals, understanding of which will be beneficial for efficient rangeland and agriculture management and establish ecosystem services in precipitation-driven drylands of Central Asia.

  7. Consumption of indigenous medicines by pregnant women in North India for selecting sex of the foetus: what can it lead to?

    PubMed

    Neogi, Sutapa Bandyopadhyay; Negandhi, Preeti H; Ganguli, Abhijit; Chopra, Sapna; Sandhu, Navraj; Gupta, Ravi Kant; Zodpey, Sanjay; Singh, Amarjeet; Singh, Arun; Gupta, Rakesh

    2015-09-04

    Sex ratio is an important indicator of development. Despite all the measures undertaken for improvement, it remains an issue of concern in India, with Haryana having a very low sex ratio in the country. Studies have been conducted indicating that consumption of indigenous drugs used for sex selection (SSD) could be strongly associated with adverse effects on the foetal development, including congenital malformations. Some samples of SSDs were collected from parts of North India and analysed in a standard laboratory for its components. Thirty SSDs used by the local community were procured from various sources in north India through a rigorous process of collection. These were subjected to laboratory tests to investigate the presence of phytoestrogen and testosterone. Following sample extraction, thin layer chromatography and high performance liquid chromatography were carried out for analysing phytoestrogen content. SSDs were available in various forms such as powder, tablets, mostly from faith healers. Around 87% of the samples collected from sources like doctors, quacks and faith healers were to be taken by the pregnant women after conception; 63% drugs were strongly positive for phytoestrogens (genistein, daidzein, formononetin) and 20% drugs were positive for testosterone. The average dose of the components as calculated after analyses was as follows: daidzein--14.1 mg/g sample, genistein--8.6 mg/g sample, formononetin--5 mg/g sample. These SSDs could be potentially detrimental to the growth and development of the foetus. This is likely to have implications on the health of the community. In view of the results obtained in our study, we strongly attest the importance in curbing this harmful practice by banning the supply of the drugs as well as by advocating behavioural changes in the community.

  8. Selection of forages by timor deer (cervus timorensis blainville) in menjangan island, bali

    NASA Astrophysics Data System (ADS)

    Ketut Ginantra, I.; Bagus Made Suaskara, Ida; Ketut Muksin, I.

    2018-03-01

    This study was conducted to determine the selection of forages plants by Timor deer (Cervus timorensis) on Menjangan Island and its relation to the availability, chemical and physical properties of feed plants. The study was conducted in July-September 2016 in savanna and monsoon forest habitats. The availability of habitat feed plants in the habitat was determined by the quadrat method, and the species of plant eaten by Timor deer was determined through the microhistological analysis of the fecal sample. The food selection index is determine by the Ivlev index. Energy contents of forages plants by bomb calorimeter apparatus, crude protein analyzed by Semi-Micro Kjeldahl technique, NDF, ADF and lignin levels refer to the method of Goering and Van Soest. Mineral content of calcium (Ca) and phosphorus (P) by using atomic absorption spectrophotometer. Determination of tannin content with Folin Denish reaction. Physical properties determine are water regain capacity and water solubility. The relationship between availability with the utilization of plants by Timor deer was analyzed with the similarity index. Multiple regression statistic to test the relationship between index selection with nutritional value factor and physical characteristic of plant species. The result showed that Timor deer selected 32 plants species of graminoids, forbs and woody plants. Feeding selection of Timor deer is strongly influenced by the availability of forage plants in habitat. The feeding selection was significantly influenced by three predictor variables i.e. positive nutritional value is crude protein and negative nutritional value were lignin and tannins. Selection of forage plant Timor deer is positively correlated with the physical properties of feed plants.

  9. How multiple mating by females affects sexual selection

    PubMed Central

    Shuster, Stephen M.; Briggs, William R.; Dennis, Patricia A.

    2013-01-01

    Multiple mating by females is widely thought to encourage post-mating sexual selection and enhance female fitness. We show that whether polyandrous mating has these effects depends on two conditions. Condition 1 is the pattern of sperm utilization by females; specifically, whether, among females, male mating number, m (i.e. the number of times a male mates with one or more females) covaries with male offspring number, o. Polyandrous mating enhances sexual selection only when males who are successful at multiple mating also sire most or all of each of their mates' offspring, i.e. only when Cov♂(m,o), is positive. Condition 2 is the pattern of female reproductive life-history; specifically, whether female mating number, m, covaries with female offspring number, o. Only semelparity does not erode sexual selection, whereas iteroparity (i.e. when Cov♀(m,o), is positive) always increases the variance in offspring numbers among females, which always decreases the intensity of sexual selection on males. To document the covariance between mating number and offspring number for each sex, it is necessary to assign progeny to all parents, as well as identify mating and non-mating individuals. To document significant fitness gains by females through iteroparity, it is necessary to determine the relative magnitudes of male as well as female contributions to the total variance in relative fitness. We show how such data can be collected, how often they are collected, and we explain the circumstances in which selection favouring multiple mating by females can be strong or weak. PMID:23339237

  10. Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis.

    PubMed

    Delaye, Luis; Ruiz-Ruiz, Susana; Calderon, Enrique; Tarazona, Sonia; Conesa, Ana; Moya, Andrés

    2018-06-01

    Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution.

  11. Amino Acid Chiral Selection Via Weak Interactions in Stellar Environments: Implications for the Origin of Life.

    PubMed

    Famiano, Michael A; Boyd, Richard N; Kajino, Toshitaka; Onaka, Takashi; Mo, Yirong

    2018-06-11

    Magnetochiral phenomena may be responsible for the selection of chiral states of biomolecules in meteoric environments. For example, the Supernova Amino Acid Processing (SNAAP) Model was proposed previously as a possible mode of magnetochiral selection of amino acids by way of the weak interaction in strong magnetic fields. In earlier work, this model was shown to produce an enantiomeric excess (ee) as high as 0.014% for alanine. In this paper we present the results of molecular quantum chemistry calculations from which ees are determined for the α-amino acids plus isovaline and norvaline, which were found to have positive ees in meteorites. Calculations are performed for both isolated and aqueous states. In some cases, the aqueous state was found to produce larger ees reaching values as high as a few percent under plausible conditions.

  12. Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity

    PubMed Central

    Zhang, Shi-Kun; Song, Jin-wen; Gong, Feng; Li, Su-Bo; Chang, Hong-Yu; Xie, Hui-Min; Gao, Hong-Wei; Tan, Ying-Xia; Ji, Shou-Ping

    2016-01-01

    AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents. PMID:27271216

  13. Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

    PubMed

    Andrews, T Daniel; Gojobori, Takashi

    2004-01-01

    The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

  14. Working Memory Replay Prioritizes Weakly Attended Events

    PubMed Central

    Penny, Will; Knight, Robert T.; Duzel, Emrah

    2017-01-01

    Abstract One view of working memory posits that maintaining a series of events requires their sequential and equal mnemonic replay. Another view is that the content of working memory maintenance is prioritized by attention. We decoded the dynamics for retaining a sequence of items using magnetoencephalography, wherein participants encoded sequences of three stimuli depicting a face, a manufactured object, or a natural item and maintained them in working memory for 5000 ms. Memory for sequence position and stimulus details were probed at the end of the maintenance period. Decoding of brain activity revealed that one of the three stimuli dominated maintenance independent of its sequence position or category; and memory was enhanced for the selectively replayed stimulus. Analysis of event-related responses during the encoding of the sequence showed that the selectively replayed stimuli were determined by the degree of attention at encoding. The selectively replayed stimuli had the weakest initial encoding indexed by weaker visual attention signals at encoding. These findings do not rule out sequential mnemonic replay but reveal that attention influences the content of working memory maintenance by prioritizing replay of weakly encoded events. We propose that the prioritization of weakly encoded stimuli protects them from interference during the maintenance period, whereas the more strongly encoded stimuli can be retrieved from long-term memory at the end of the delay period. PMID:28824955

  15. Adaptive evolution of tight junction protein claudin-14 in echolocating whales.

    PubMed

    Xu, Huihui; Liu, Yang; He, Guimei; Rossiter, Stephen J; Zhang, Shuyi

    2013-11-10

    Toothed whales and bats have independently evolved specialized ultrasonic hearing for echolocation. Recent findings have suggested that several genes including Prestin, Tmc1, Pjvk and KCNQ4 appear to have undergone molecular adaptations associated with the evolution of this ultrasonic hearing in mammals. Here we studied the hearing gene Cldn14, which encodes the claudin-14 protein and is a member of tight junction proteins that functions in the organ of Corti in the inner ear to maintain a cationic gradient between endolymph and perilymph. Particular mutations in human claudin-14 give rise to non-syndromic deafness, suggesting an essential role in hearing. Our results uncovered two bursts of positive selection, one in the ancestral branch of all toothed whales and a second in the branch leading to the delphinid, phocoenid and ziphiid whales. These two branches are the same as those previously reported to show positive selection in the Prestin gene. Furthermore, as with Prestin, the estimated hearing frequencies of whales significantly correlate with numbers of branch-wise non-synonymous substitutions in Cldn14, but not with synonymous changes. However, in contrast to Prestin, we found no evidence of positive selection in bats. Our findings from Cldn14, and comparisons with Prestin, strongly implicate multiple loci in the acquisition of echolocation in cetaceans, but also highlight possible differences in the evolutionary route to echolocation taken by whales and bats. © 2013.

  16. The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

    NASA Astrophysics Data System (ADS)

    Bayliss, Matthew

    2017-08-01

    We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics |*| the infamous |*|gastrophysics|*| in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

  17. The Chandra Strong Lens Sample: Revealing Baryonic Physics In Strong Lensing Selected Clusters

    NASA Astrophysics Data System (ADS)

    Bayliss, Matthew

    2017-09-01

    We propose for Chandra imaging of the hot intra-cluster gas in a unique new sample of 29 galaxy clusters selected purely on their strong gravitational lensing signatures. This will be the first program targeting a purely strong lensing selected cluster sample, enabling new comparisons between the ICM properties and scaling relations of strong lensing and mass/ICM selected cluster samples. Chandra imaging, combined with high precision strong lens models, ensures powerful constraints on the distribution and state of matter in the cluster cores. This represents a novel angle from which we can address the role played by baryonic physics -- the infamous ``gastrophysics''-- in shaping the cores of massive clusters, and opens up an exciting new galaxy cluster discovery space with Chandra.

  18. A thrifty variant in CREBRF strongly influences body mass index in Samoans

    PubMed Central

    Kershaw, Erin E; Cheng, Hong; Buhule, Olive D; Lin, Jerome; Reupena, Muagututi‘a Sefuiva; Viali, Satupa‘itea; Tuitele, John; Naseri, Take; Urban, Zsolt; Deka, Ranjan; Weeks, Daniel E; McGarvey, Stephen T

    2016-01-01

    Samoans are a unique founder population with a high prevalence of obesity1–3, making them well suited for identifying new genetic contributors to obesity4. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10−14), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10−20). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36–1.45 kg/m2 per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity. PMID:27455349

  19. Rampant Gene Exchange Across a Strong Reproductive Barrier Between the Annual Sunflowers, Helianthus annuus and H. petiolaris

    PubMed Central

    Yatabe, Yoko; Kane, Nolan C.; Scotti-Saintagne, Caroline; Rieseberg, Loren H.

    2007-01-01

    Plant species may remain morphologically distinct despite gene exchange with congeners, yet little is known about the genomewide pattern of introgression among species. Here we analyze the effects of persistent gene flow on genomic differentiation between the sympatric sunflower species Helianthus annuus and H. petiolaris. While the species are strongly isolated in testcrosses, genetic distances at 108 microsatellite loci and 14 sequenced genes are highly variable and much lower (on average) than for more closely related but historically allopatric congeners. Our analyses failed to detect a positive association between levels of genetic differentiation and chromosomal rearrangements (as reported in a prior publication) or proximity to QTL for morphological differences or hybrid sterility. However, a significant increase in differentiation was observed for markers within 5 cM of chromosomal breakpoints. Together, these results suggest that islands of differentiation between these two species are small, except in areas of low recombination. Furthermore, only microsatellites associated with ESTs were identified as outlier loci in tests for selection, which might indicate that the ESTs themselves are the targets of selection rather than linked genes (or that coding regions are not randomly distributed). In general, these results indicate that even strong and genetically complex reproductive barriers cannot prevent widespread introgression. PMID:17277373

  20. Persistent directional selection on body size and a resolution to the paradox of stasis.

    PubMed

    Rollinson, Njal; Rowe, Locke

    2015-09-01

    Directional selection on size is common but often fails to result in microevolution in the wild. Similarly, macroevolutionary rates in size are low relative to the observed strength of selection in nature. We show that many estimates of selection on size have been measured on juveniles, not adults. Further, parents influence juvenile size by adjusting investment per offspring. In light of these observations, we help resolve this paradox by suggesting that the observed upward selection on size is balanced by selection against investment per offspring, resulting in little or no net selection gradient on size. We find that trade-offs between fecundity and juvenile size are common, consistent with the notion of selection against investment per offspring. We also find that median directional selection on size is positive for juveniles but no net directional selection exists for adult size. This is expected because parent-offspring conflict exists over size, and juvenile size is more strongly affected by investment per offspring than adult size. These findings provide qualitative support for the hypothesis that upward selection on size is balanced by selection against investment per offspring, where parent-offspring conflict over size is embodied in the opposing signs of the two selection gradients. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  1. Sex steroids, sexual behavior, and selection attention for erotic stimuli in women using oral contraceptives.

    PubMed

    Alexander, G M; Sherwin, B B

    1993-01-01

    The relationship between sex steroids and sexual behavior was examined in 19 oral contraceptive users. Retrospective assessment of sexual attitudes were obtained and women completed daily ratings of sexual behavior and well-being for 28 days. Plasma levels of free testosterone (T), estradiol, and progesterone were measured at weekly intervals. In addition, women performed a novel selective attention task designed to measure the strength of the tendency to be distracted by sexual stimuli. Multiple regression analyses using average sexual behavior variables as dependent variables, and hormone levels sexual attitudes and well-being as predictor variables, showed that free T was strongly and positively associated with sexual desire, sexual thoughts, and anticipation of sexual activity. A role for T in attention to sexual stimuli was also supported by the positive correlation between free T and the bias for sexual stimuli in a subgroup of women. These results are consistent with the hypothesis that T may enhance cognitive aspects of women's sexual behavior.

  2. Genome-Wide Analyses Reveal Genes Subject to Positive Selection in Pasteurella multocida

    PubMed Central

    Cao, Peili; Guo, Dongchun; Liu, Jiasen; Jiang, Qian; Xu, Zhuofei; Qu, Liandong

    2017-01-01

    Pasteurella multocida, a Gram-negative opportunistic pathogen, has led to a broad range of diseases in mammals and birds, including fowl cholera in poultry, pneumonia and atrophic rhinitis in swine and rabbit, hemorrhagic septicemia in cattle, and bite infections in humans. In order to better interpret the genetic diversity and adaptation evolution of this pathogen, seven genomes of P. multocida strains isolated from fowls, rabbit and pigs were determined by using high-throughput sequencing approach. Together with publicly available P. multocida genomes, evolutionary features were systematically analyzed in this study. Clustering of 70,565 protein-coding genes showed that the pangenome of 33 P. multocida strains was composed of 1,602 core genes, 1,364 dispensable genes, and 1,070 strain-specific genes. Of these, we identified a full spectrum of genes related to virulence factors and revealed genetic diversity of these potential virulence markers across P. multocida strains, e.g., bcbAB, fcbC, lipA, bexDCA, ctrCD, lgtA, lgtC, lic2A involved in biogenesis of surface polysaccharides, hsf encoding autotransporter adhesin, and fhaB encoding filamentous haemagglutinin. Furthermore, based on genome-wide positive selection scanning, a total of 35 genes were subject to strong selection pressure. Extensive analyses of protein subcellular location indicated that membrane-associated genes were highly abundant among all positively selected genes. The detected amino acid sites undergoing adaptive selection were preferably located in extracellular space, perhaps associated with bacterial evasion of host immune responses. Our findings shed more light on conservation and distribution of virulence-associated genes across P. multocida strains. Meanwhile, this study provides a genetic context for future researches on the mechanism of adaptive evolution in P. multocida. PMID:28611758

  3. Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Nonsynonymous Variant at SLC39A8 in Europeans.

    PubMed

    Li, Ming; Wu, Dong-Dong; Yao, Yong-Gang; Huo, Yong-Xia; Liu, Jie-Wei; Su, Bing; Chasman, Daniel I; Chu, Audrey Y; Huang, Tao; Qi, Lu; Zheng, Yan; Luo, Xiong-Jian

    2016-01-01

    Natural selection has played important roles in optimizing complex human adaptations. However, schizophrenia poses an evolutionary paradox during human evolution, as the illness has strongly negative effects on fitness, but persists with a prevalence of ~0.5% across global populations. Recent studies have identified numerous risk variations in diverse populations, which might be able to explain the stable and high rate of schizophrenia morbidity in different cultures and regions, but the questions about why the risk alleles derived and maintained in human gene pool still remain unsolved. Here, we studied the evolutionary pattern of a schizophrenia risk variant rs13107325 (P < 5.0 × 10(-8) in Europeans) in the SLC39A8 gene. We found the SNP is monomorphic in Asians and Africans with risk (derived) T-allele totally absent, and further evolutionary analyses showed the T-allele has experienced recent positive selection in Europeans. Subsequent exploratory analyses implicated that the colder environment in Europe was the likely selective pressures, ie, when modern humans migrated "out of Africa" and moved to Europe mainland (a colder and cooler continent than Africa), new alleles derived due to positive selection and protected humans from risk of hypertension and also helped them adapt to the cold environment. The hypothesis was supported by our pleiotropic analyses with hypertension and energy intake as well as obesity in Europeans. Our data thus provides an intriguing example to illustrate a possible mechanism for maintaining schizophrenia risk alleles in the human gene pool, and further supported that schizophrenia is likely a product caused by pleiotropic effect during human evolution. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Evidence of evolutionary history and selective sweeps in the genome of Meishan pig reveals its genetic and phenotypic characterization.

    PubMed

    Zhao, Pengju; Yu, Ying; Feng, Wen; Du, Heng; Yu, Jian; Kang, Huimin; Zheng, Xianrui; Wang, Zhiquan; Liu, George E; Ernst, Catherine W; Ran, Xueqin; Wang, Jiafu; Liu, Jian-Feng

    2018-05-01

    Meishan is a pig breed indigenous to China and famous for its high fecundity. The traits of Meishan are strongly associated with its distinct evolutionary history and domestication. However, the genomic evidence linking the domestication of Meishan pigs with its unique features is still poorly understood. The goal of this study is to investigate the genomic signatures and evolutionary evidence related to the phenotypic traits of Meishan via large-scale sequencing. We found that the unique domestication of Meishan pigs occurred in the Taihu Basin area between the Majiabang and Liangzhu Cultures, during which 300 protein-coding genes have underwent positive selection. Notably, enrichment of the FoxO signaling pathway with significant enrichment signal and the harbored gene IGF1R were likely associated with the high fertility of Meishan pigs. Moreover, NFKB1 exhibited strong selective sweep signals and positively participated in hyaluronan biosynthesis as the key gene of NF-kB signaling, which may have resulted in the wrinkled skin and face of Meishan pigs. Particularly, three population-specific synonymous single-nucleotide variants occurred in PYROXD1, MC1R, and FAM83G genes; the T305C substitution in the MCIR gene explained the black coat of the Meishan pigs well. In addition, the shared haplotypes between Meishan and Duroc breeds confirmed the previous Asian-derived introgression and demonstrated the specific contribution of Meishan pigs. These findings will help us explain the unique genetic and phenotypic characteristics of Meishan pigs and offer a plausible method for their utilization of Meishan pigs as valuable genetic resources in pig breeding and as an animal model for human wrinkled skin disease research.

  5. Variable terrestrial GPS telemetry detection rates: Addressing the probability of successful acquisitions

    USGS Publications Warehouse

    Ironside, Kirsten E.; Mattson, David J.; Choate, David; Stoner, David; Arundel, Terry; Hansen, Jered R.; Theimer, Tad; Holton, Brandon; Jansen, Brian; Sexton, Joseph O.; Longshore, Kathleen M.; Edwards, Thomas C.; Peters, Michael

    2017-01-01

    Studies using global positioning system (GPS) telemetry rarely result in 100% fix success rates (FSR), which may bias datasets because data loss is systematic rather than a random process. Previous spatially explicit models developed to correct for sampling bias have been limited to small study areas, a small range of data loss, or were study-area specific. We modeled environmental effects on FSR from desert to alpine biomes, investigated the full range of potential data loss (0–100% FSR), and evaluated whether animal body position can contribute to lower FSR because of changes in antenna orientation based on GPS detection rates for 4 focal species: cougars (Puma concolor), desert bighorn sheep (Ovis canadensis nelsoni), Rocky Mountain elk (Cervus elaphus nelsoni), and mule deer (Odocoileus hemionus). Terrain exposure and height of over story vegetation were the most influential factors affecting FSR. Model evaluation showed a strong correlation (0.88) between observed and predicted FSR and no significant differences between predicted and observed FSRs using 2 independent validation datasets. We found that cougars and canyon-dwelling bighorn sheep may select for environmental features that influence their detectability by GPS technology, mule deer may select against these features, and elk appear to be nonselective. We observed temporal patterns in missed fixes only for cougars. We provide a model for cougars, predicting fix success by time of day that is likely due to circadian changes in collar orientation and selection of daybed sites. We also provide a model predicting the probability of GPS fix acquisitions given environmental conditions, which had a strong relationship (r 2 = 0.82) with deployed collar FSRs across species.

  6. Development of an indirect enzyme-linked immunosorbent assay test for detecting antibodies to chicken astrovirus in chicken sera.

    PubMed

    Skibinska, A; Lee, A; Wylie, M; Smyth, V J; Welsh, M D; Todd, D

    2015-01-01

    The development of an indirect enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of Group B chicken astrovirus (CAstV) infections is described. The test was based on the use of an affinity-purified capsid antigen, specific to CAstV isolate 11672, produced as a glutathione-S-transferase N-terminal fusion protein by a recombinant baculovirus. Strongly positive ELISA signals were elicited against experimentally produced antisera raised to CAstVs from Group B (subgroups i and ii) but were negative for antisera raised to a Group A CAstV. Using a panel of 240 selected serum samples, 99% agreement was observed when the results obtained by ELISA were compared to those from an indirect immunofluorescence test for CAstV 11672. The ELISA test was applied to 68 serum sets comprising 1864 samples, which were obtained from parent and grandparent flocks originating mainly in the UK. Of the 52 sets containing ELISA-positive samples, 24 sets had >75% samples positive and nine sets had <25% samples positive and were regarded as having high and low seropositivities, respectively. Of the 1864 serum samples tested 1090 (58.5%) were ELISA positive and of these, 234 sera (21.5%) produced strongly positive signals, whereas moderately positive and weakly positive signals were produced by 562 (51.5%) and 294 (27%) sera. When used for flock screening purposes, this ELISA test can be used to (i) investigate the occurrence of first-time CAstV infections of parent flocks during lay and the possible adverse effects caused by vertically transmitted CAstV infections on broiler hatchability and performance and (ii) diagnose Group B CAstV infections within specific pathogen free flocks.

  7. Statistical Investigations on Solar Wind Dynamic Pressure Pulses:Basic features and Their Impacts on Geosynchronous Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Zuo, Pingbing; Feng, Xueshang

    2016-07-01

    Solar wind dynamic pressure pulse (DPP) structures, across which the dynamic pressure abruptly changes over timescales from a few seconds to several minutes, are often observed in the near-Earth space environment. Recently we have developed a novel procedure that is able to rapidly identify the DPPs from the plasma data stream, and simultaneously define the transition region and smartly select the upstream and downstream region for analysis. The plasma data with high time-resolution from 3DP instrument on board the WIND spacecraft are inspected with this automatic DPP-searching code, and a complete list of solar wind DPPs of historic WIND observations are built up. We perform a statistical survey on the properties of DPPs near 1 AU based on this event list. It is found that overwhelming majority of DPPs are associated with the solar wind disturbances including the CME-related flows, the corotating interaction regions, as well as the complex ejecta. The annual variations of the averaged occurrence rate of DPPs are roughly in phase with the solar activities. Although the variabilities of geosynchronous magnetic fields (GMFs) due to the impact of positive DPPs have been well established, there appears no systematic investigations on the response of GMFs to negative DPPs. Here we also study the decompression/compression effects of very strong negative/positive DPPs on GMFs under northward IMFs. In response to the decompression of strong negative DPPs, GMFs on dayside, near the dawn and dusk on nightside are generally depressed. But near the midnight region, the responses of GMF are very diverse, being either positive or negative. For part of events when GOES is located at the midnight sector, GMF is found to abnormally increase as the result of magnetospheric decompression caused by negative DPPs. It is known that on certain conditions magnetic depression of nightside GMFs can be caused by the impact of positive DPPs. Statistically, both the decompression effect of strong negative DPPs and the compression effect of strong positive DPPs depend on the magnetic local time, being stronger at the noon sector.

  8. Population mitogenomics provides insights into evolutionary history, source of invasions and diversifying selection in the House Crow (Corvus splendens).

    PubMed

    Krzemińska, Urszula; Morales, Hernán E; Greening, Chris; Nyári, Árpád S; Wilson, Robyn; Song, Beng Kah; Austin, Christopher M; Sunnucks, Paul; Pavlova, Alexandra; Rahman, Sadequr

    2018-04-01

    The House Crow (Corvus splendens) is a useful study system for investigating the genetic basis of adaptations underpinning successful range expansion. The species originates from the Indian subcontinent, but has successfully spread through a variety of thermal environments across Asia, Africa and Europe. Here, population mitogenomics was used to investigate the colonisation history and to test for signals of molecular selection on the mitochondrial genome. We sequenced the mitogenomes of 89 House Crows spanning four native and five invasive populations. A Bayesian dated phylogeny, based on the 13 mitochondrial protein-coding genes, supports a mid-Pleistocene (~630,000 years ago) divergence between the most distant genetic lineages. Phylogeographic patterns suggest that northern South Asia is the likely centre of origin for the species. Codon-based analyses of selection and assessments of changes in amino acid properties provide evidence of positive selection on the ND2 and ND5 genes against a background of purifying selection across the mitogenome. Protein homology modelling suggests that four amino acid substitutions inferred to be under positive selection may modulate coupling efficiency and proton translocation mediated by OXPHOS complex I. The identified substitutions are found within native House Crow lineages and ecological niche modelling predicts suitable climatic areas for the establishment of crow populations within the invasive range. Mitogenomic patterns in the invasive range of the species are more strongly associated with introduction history than climate. We speculate that invasions of the House Crow have been facilitated by standing genetic variation that accumulated due to diversifying selection within the native range.

  9. Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

    USGS Publications Warehouse

    Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

    2016-01-01

    Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

  10. Contrasting evolutionary histories of MHC class I and class II loci in grouse—effects of selection and gene conversion

    PubMed Central

    Minias, P; Bateson, Z W; Whittingham, L A; Johnson, J A; Oyler-McCance, S; Dunn, P O

    2016-01-01

    Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens. PMID:26860199

  11. Does fluoride influence oviposition of Anopheles stephensi in stored water habitats in an urban setting?

    PubMed

    Thomas, Shalu; Ravishankaran, Sangamithra; Johnson Amala Justin, N A; Asokan, Aswin; Maria Jusler Kalsingh, T; Mathai, Manu Thomas; Valecha, Neena; Eapen, Alex

    2016-11-09

    The physico-chemical characteristics of lentic aquatic habitats greatly influence mosquito species in selecting suitable oviposition sites; immature development, pupation and adult emergence, therefore are considerations for their preferred ecological niche. Correlating water quality parameters with mosquito breeding, as well as immature vector density, are useful for vector control operations in identifying and targeting potential breeding habitats. A total of 40 known habitats of Anopheles stephensi, randomly selected based on a vector survey in parallel, were inspected for the physical and chemical nature of the aquatic environment. Water samples were collected four times during 2013, representing four seasons (i.e., ten habitats per season). The physico-chemical variables and mosquito breeding were statistically analysed to find their correlation with immature density of An. stephensi and also co-inhabitation with other mosquito species. Anopheles stephensi prefer water with low nitrite content and high phosphate content. Parameters such as total dissolved solids, electrical conductivity, total hardness, chloride, fluoride and sulfate had a positive correlation in habitats with any mosquito species breeding (p < 0.05) and also in habitats with An. stephensi alone breeding. Fluoride was observed to have a strong positive correlation with immature density of An. stephensi in both overhead tanks and wells. Knowledge of larval ecology of vector mosquitoes is a key factor in risk assessment and for implementing appropriate and sustainable vector control operations. The presence of fluoride in potential breeding habitats and a strong positive correlation with An. stephensi immature density is useful information, as fluoride can be considered an indicator/predictor of vector breeding. Effective larval source management can be focussed on specified habitats in vulnerable areas to reduce vector abundance and malaria transmission.

  12. Testes Mass, but Not Sperm Length, Increases with Higher Levels of Polyandry in an Ancient Sex Model

    PubMed Central

    Vrech, David E.; Olivero, Paola A.; Mattoni, Camilo I.; Peretti, Alfredo V.

    2014-01-01

    There is strong evidence that polyandrous taxa have evolved relatively larger testes than monogamous relatives. Sperm size may either increase or decrease across species with the risk or intensity of sperm competition. Scorpions represent an ancient direct mode with spermatophore-mediated sperm transfer and are particularly well suited for studies in sperm competition. This work aims to analyze for the first time the variables affecting testes mass, ejaculate volume and sperm length, according with their levels of polyandry, in species belonging to the Neotropical family Bothriuridae. Variables influencing testes mass and sperm length were obtained by model selection analysis using corrected Akaike Information Criterion. Testes mass varied greatly among the seven species analyzed, ranging from 1.6±1.1 mg in Timogenes dorbignyi to 16.3±4.5 mg in Brachistosternus pentheri with an average of 8.4±5.0 mg in all the species. The relationship between testes mass and body mass was not significant. Body allocation in testes mass, taken as Gonadosomatic Index, was high in Bothriurus cordubensis and Brachistosternus ferrugineus and low in Timogenes species. The best-fitting model for testes mass considered only polyandry as predictor with a positive influence. Model selection showed that body mass influenced sperm length negatively but after correcting for body mass, none of the variables analyzed explained sperm length. Both body mass and testes mass influenced spermatophore volume positively. There was a strong phylogenetic effect on the model containing testes mass. As predicted by the sperm competition theory and according to what happens in other arthropods, testes mass increased in species with higher levels of sperm competition, and influenced positively spermatophore volume, but data was not conclusive for sperm length. PMID:24736525

  13. Photic niche invasions: phylogenetic history of the dim-light foraging augochlorine bees (Halictidae)

    PubMed Central

    Tierney, Simon M.; Sanjur, Oris; Grajales, Grethel G.; Santos, Leandro M.; Bermingham, Eldredge; Wcislo, William T.

    2012-01-01

    Most bees rely on flowering plants and hence are diurnal foragers. From this ancestral state, dim-light foraging in bees requires significant adaptations to a new photic environment. We used DNA sequences to evaluate the phylogenetic history of the most diverse clade of Apoidea that is adapted to dim-light environments (Augochlorini: Megalopta, Megaloptidia and Megommation). The most speciose lineage, Megalopta, is distal to the remaining dim-light genera, and its closest diurnal relative (Xenochlora) is recovered as a lineage that has secondarily reverted to diurnal foraging. Tests for adaptive protein evolution indicate that long-wavelength opsin shows strong evidence of stabilizing selection, with no more than five codons (2%) under positive selection, depending on analytical procedure. In the branch leading to Megalopta, the amino acid of the single positively selected codon is conserved among ancestral Halictidae examined, and is homologous to codons known to influence molecular structure at the chromophore-binding pocket. Theoretically, such mutations can shift photopigment λmax sensitivity and enable visual transduction in alternate photic environments. Results are discussed in light of the available evidence on photopigment structure, morphological specialization and biogeographic distributions over geological time. PMID:21795273

  14. Photic niche invasions: phylogenetic history of the dim-light foraging augochlorine bees (Halictidae).

    PubMed

    Tierney, Simon M; Sanjur, Oris; Grajales, Grethel G; Santos, Leandro M; Bermingham, Eldredge; Wcislo, William T

    2012-02-22

    Most bees rely on flowering plants and hence are diurnal foragers. From this ancestral state, dim-light foraging in bees requires significant adaptations to a new photic environment. We used DNA sequences to evaluate the phylogenetic history of the most diverse clade of Apoidea that is adapted to dim-light environments (Augochlorini: Megalopta, Megaloptidia and Megommation). The most speciose lineage, Megalopta, is distal to the remaining dim-light genera, and its closest diurnal relative (Xenochlora) is recovered as a lineage that has secondarily reverted to diurnal foraging. Tests for adaptive protein evolution indicate that long-wavelength opsin shows strong evidence of stabilizing selection, with no more than five codons (2%) under positive selection, depending on analytical procedure. In the branch leading to Megalopta, the amino acid of the single positively selected codon is conserved among ancestral Halictidae examined, and is homologous to codons known to influence molecular structure at the chromophore-binding pocket. Theoretically, such mutations can shift photopigment λ(max) sensitivity and enable visual transduction in alternate photic environments. Results are discussed in light of the available evidence on photopigment structure, morphological specialization and biogeographic distributions over geological time.

  15. Plant Rhizosphere Selection of Plasmodiophorid Lineages from Bulk Soil: The Importance of “Hidden” Diversity

    PubMed Central

    Bass, David; van der Gast, Christopher; Thomson, Serena; Neuhauser, Sigrid; Hilton, Sally; Bending, Gary D.

    2018-01-01

    Microbial communities closely associated with the rhizosphere can have strong positive and negative impacts on plant health and growth. We used a group-specific amplicon approach to investigate local scale drivers in the diversity and distribution of plasmodiophorids in rhizosphere/root and bulk soil samples from oilseed rape (OSR) and wheat agri-systems. Plasmodiophorids are plant- and stramenopile-associated protists including well known plant pathogens as well as symptomless endobiotic species. We detected 28 plasmodiophorid lineages (OTUs), many of them novel, and showed that plasmodiophorid communities were highly dissimilar and significantly divergent between wheat and OSR rhizospheres and between rhizosphere and bulk soil samples. Bulk soil communities were not significantly different between OSR and wheat systems. Wheat and OSR rhizospheres selected for different plasmodiophorid lineages. An OTU corresponding to Spongospora nasturtii was positively selected in the OSR rhizosphere, as were two genetically distinct OTUs. Two novel lineages related to Sorosphaerula veronicae were significantly associated with wheat rhizosphere samples, indicating unknown plant-protist relationships. We show that group-targeted eDNA approaches to microbial symbiont-host ecology reveal significant novel diversity and enable inference of differential activity and potential interactions between sequence types, as well as their presence. PMID:29503632

  16. Interaction intensity and pollinator-mediated selection.

    PubMed

    Trunschke, Judith; Sletvold, Nina; Ågren, Jon

    2017-05-01

    In animal-pollinated plants, the opportunity for selection and the strength of pollinator-mediated selection are expected to increase with the degree of pollen limitation. However, whether differences in pollen limitation can explain variation in pollinator-mediated and net selection among animal-pollinated species is poorly understood. In the present study, we quantified pollen limitation, variance in relative fitness and pollinator-mediated selection on five traits important for pollinator attraction (flowering start, plant height, flower number, flower size) and pollination efficiency (spur length) in natural populations of 12 orchid species. Pollinator-mediated selection was quantified by subtracting estimates of selection gradients for plants receiving supplemental hand-pollination from estimates obtained for open-pollinated control plants. Mean pollen limitation ranged from zero to 0.96. Opportunity for selection, pollinator-mediated selection and net selection were all positively related to pollen limitation, whereas nonpollinator-mediated selection was not. Opportunity for selection varied five-fold, strength of pollinator-mediated selection varied three-fold and net selection varied 1.5-fold among species. Supplemental hand-pollination reduced both opportunity for selection and selection on floral traits. The results show that the intensity of biotic interactions is an important determinant of the selection regime, and indicate that the potential for pollinator-mediated selection and divergence in floral traits is particularly high in species that are strongly pollen-limited. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  17. Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

    PubMed Central

    Rockenbach, Kate; Havird, Justin C.; Monroe, J. Grey; Triant, Deborah A.; Taylor, Douglas R.; Sloan, Daniel B.

    2016-01-01

    Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastid–nuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid–nuclear conflict as a novel cause of accelerated evolution. PMID:27707788

  18. The effects of stress and sex on selection, genetic covariance, and the evolutionary response.

    PubMed

    Holman, L; Jacomb, F

    2017-10-01

    The capacity of a population to adapt to selection (evolvability) depends on whether the structure of genetic variation permits the evolution of fitter trait combinations. Selection, genetic variance and genetic covariance can change under environmental stress, and males and females are not genetically independent, yet the combined effects of stress and dioecy on evolvability are not well understood. Here, we estimate selection, genetic (co)variance and evolvability in both sexes of Tribolium castaneum flour beetles under stressful and benign conditions, using a half-sib breeding design. Although stress uncovered substantial latent heritability, stress also affected genetic covariance, such that evolvability remained low under stress. Sexual selection on males and natural selection on females favoured a similar phenotype, and there was positive intersex genetic covariance. Consequently, sexual selection on males augmented adaptation in females, and intralocus sexual conflict was weak or absent. This study highlights that increased heritability does not necessarily increase evolvability, suggests that selection can deplete genetic variance for multivariate trait combinations with strong effects on fitness, and tests the recent hypothesis that sexual conflict is weaker in stressful or novel environments. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  19. Frugivorous bats maintain functional habitat connectivity in agricultural landscapes but rely strongly on natural forest fragments.

    PubMed

    Ripperger, Simon P; Kalko, Elisabeth K V; Rodríguez-Herrera, Bernal; Mayer, Frieder; Tschapka, Marco

    2015-01-01

    Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae), a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.

  20. Nucleotide variation at the dopa decarboxylase (Ddc) gene in natural populations of Drosophila melanogaster.

    PubMed

    Tatarenkov, Andrey; Ayala, Francisco J

    2007-08-01

    We studied nucleotide sequence variation at the gene coding for dopa decarboxylase (Ddc) in seven populations of Drosophila melanogaster. Strength and pattern of linkage disequilibrium are somewhat distinct in the extensively sampled Spanish and Raleigh populations. In the Spanish population, a few sites are in strong positive association, whereas a large number of sites in the Raleigh population are associated nonrandomly but the association is not strong. Linkage disequilibrium analysis shows presence of two groups of haplotypes in the populations, each of which is fairly diverged, suggesting epistasis or inversion polymorphism. There is evidence of two forms of natural selection acting on Ddc. The McDonald-Kreitman test indicates a deficit of fixed amino acid differences between D. melanogaster and D. simulans, which may be due to negative selection. An excess of derived alleles at high frequency, significant according to the H-test, is consistent with the effect of hitchhiking. The hitchhiking may have been caused by directional selection downstream of the locus studied, as suggested by a gradual decrease of the polymorphism-to-divergence ratio. Altogether, the Ddc locus exhibits a complicated pattern of variation apparently due to several evolutionary forces. Such a complex pattern may be a result of an unusually high density of functionally important genes.

  1. High polymorphism in MHC-DRB genes in golden snub-nosed monkeys reveals balancing selection in small, isolated populations.

    PubMed

    Zhang, Pei; Huang, Kang; Zhang, Bingyi; Dunn, Derek W; Chen, Dan; Li, Fan; Qi, Xiaoguang; Guo, Songtao; Li, Baoguo

    2018-03-13

    Maintaining variation in immune genes, such as those of the major histocompatibility complex (MHC), is important for individuals in small, isolated populations to resist pathogens and parasites. The golden snub-nosed monkey (Rhinopithecus roxellana), an endangered primate endemic to China, has experienced a rapid reduction in numbers and severe population fragmentation over recent years. For this study, we measured the DRB diversity among 122 monkeys from three populations in the Qinling Mountains, and estimated the relative importance of different agents of selection in maintaining variation of DRB genes. We identified a total of 19 DRB sequences, in which five alleles were novel. We found high DRB variation in R. roxellana and three branches of evidence suggesting that balancing selection has contributed to maintaining MHC polymorphism over the long term in this species: i) different patterns of both genetic diversity and population differentiation were detected at MHC and neutral markers; ii) an excess of non-synonymous substitutions compared to synonymous substitutions at antigen binding sites, and maximum-likelihood-based random-site models, showed significant positive selection; and iii) phylogenetic analyses revealed a pattern of trans-species evolution for DRB genes. High levels of DRB diversity in these R. roxellana populations may reflect strong selection pressure in this species. Patterns of genetic diversity and population differentiation, positive selection, as well as trans-species evolution, suggest that pathogen-mediated balancing selection has contributed to maintaining MHC polymorphism in R. roxellana over the long term. This study furthers our understanding of the role pathogen-mediated balancing selection has in maintaining variation in MHC genes in small and fragmented populations of free-ranging vertebrates.

  2. Flicker Vision of Selected Light Sources

    NASA Astrophysics Data System (ADS)

    Otomański, Przemysław; Wiczyński, Grzegorz; Zając, Bartosz

    2017-10-01

    The results of the laboratory research concerning a dependence of flicker vision on voltage fluctuations are presented in the paper. The research was realized on a designed measuring stand, which included an examined light source, a voltage generator with amplitude modulation supplying the light source and a positioning system of the observer with respect to the observed surface. In this research, the following light sources were used: one incandescent lamp and four LED luminaires by different producers. The research results formulate a conclusion concerning the description of the influence of voltage fluctuations on flicker viewing for selected light sources. The research results indicate that LED luminaires are less susceptible to voltage fluctuations than incandescent bulbs and that flicker vision strongly depends on the type of LED source.

  3. Damage assessment of RC buildings subjected to the different strong motion duration

    NASA Astrophysics Data System (ADS)

    Mortezaei, Alireza; mohajer Tabrizi, Mohsen

    2015-07-01

    An earthquake has three important characteristics; namely, amplitude, frequency content and duration. Amplitude and frequency content have a direct impact but not necessarily the sole cause of structural damage. Regarding the duration, some researchers show a high correlation between strong motion duration and structural damage whereas some others find no relation. This paper focuses on the ground motion durations characterized by Arias Intensity (AI). High duration may increase the damage state of structure for the damage accumulation. This paper investigates the response time histories (acceleration, velocity and displacement) of RC buildings under the different strong motion durations. Generally, eight earthquake records were selected from different soil type, and these records were grouped according to their PGA and frequency ranges. Maximum plastic rotation and drift response was chosen as damage indicator. In general, there was a positive correlation between strong motion duration and damage; however, in some PGA and frequency ranges input motions with shorter durations might cause more damage than the input motions with longer durations. In soft soils, input motions with longer durations caused more damage than the input motions with shorter durations.

  4. Analysis of damaging process and crack propagation

    NASA Astrophysics Data System (ADS)

    Semenski, D.; Wolf, H.; Božić, Ž.

    2010-06-01

    Supervising and health monitoring of structures can assess the actual state of existing structures after initial loading or in the state of operation. Structural life management requires the integration of design and analysis, materials behavior and structural testing, as given for several examples. Procedure of survey of structural elements and criteria for their selection must be strongly defined as it is for the offshore gas platforms. Numerical analysis of dynamic loading is shown for the Aeolian vibrations of overhead transmission line conductors. Since the damper’s efficiency strongly depends on its position, the procedure of determining the optimum position of the damper is described. The optical method of caustics is established in isotropic materials for determination of the stress intensity factors (SIFs) of the cracks in deformed structures and is advantageously improved for the application to fiberreinforced composites. A procedure for simulation of crack propagation for multiple cracks was introduced and SIFs have been calculated by using finite element method. Crack growth of a single crack or a periodical array of cracks initiated at the stiffeners in a stiffened panel has been investigated.

  5. Factors affecting the use of contraception in Bangladesh: a multivariate analysis.

    PubMed

    Ullah, M S; Chakraborty, N

    1993-09-01

    The government of Bangladesh since independence has tried to strengthen the national family planning program. Using data from the 1989 Bangladesh Fertility Survey on a nationally representative sample of 7984 rural and urban households, the authors consider fifteen socioeconomic and demographic variables and assess their relative importance in relation to current contraceptive use. The data indicate that 31.1% of younger and lower parity women use contraceptives. Women's education, followed by women's participation in family planning decision making, were the most important of selected factors which positively affect current use of contraception. Administrative division, desire for additional children, urban residence, and family planning worker visits were also important factors significantly and positively related to the current use of contraception. Husband's occupation was strongly associated with contraceptive use. Child loss, however, was negatively associated with contraceptive use, followed by sex composition of living children. The authors suggest that women should be encouraged to participate in family decisions, and become informed about their rights, privileges, and family law. Finally, it was found that education makes less difference to contraceptive use where family planning programs are strong.

  6. Modulating the selectivity of affinity absorbents to multi-phosphopeptides by a competitive substitution strategy.

    PubMed

    Liu, Zheyi; Wang, Fangjun; Chen, Jin; Zhou, Ye; Zou, Hanfa

    2016-08-26

    Although many affinity adsorbents have been developed for phosphopeptides enrichment, high-specifically capturing the multi-phosphopeptides is still a big challenge. Here, we investigated the mechanism of phosphate ion coordination and substitution on affinity adsorbents surfaces and modulated the selectivity of affinity adsorbents to multi-phosphopeptides based on the different capability of mono- and multi-phosphopeptides in competitively substituting the pre-coordinated phosphate ions at strong acidic condition. We demonstrated both the species of pre-coordinated phosphate ions and the substituting conditions played crucial roles in modulating the enrichment selectivity to multi-phosphopeptides, and the pre-coordinated affinity materials with relative more surfaces positive charges exhibited better enrichment efficiency due to the cooperative effect of electrostatic interaction and competitive substitution. Finally, an enrichment selectivity of 85% to multi-phosphopeptides was feasibly achieved with 66% improvement in identification numbers for complex protein sample extracted from HepG2 cells. Data are available via ProteomeXchange with identifier PXD004252. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Food preferences of larvae of Antarctic silverfish Pleuragramma antarcticum Boulenger, 1902 from Terre Adélie coastal waters during summer 2004

    NASA Astrophysics Data System (ADS)

    Vallet, Carole; Beans, Cristina; Koubbi, Philippe; Courcot, Lucie; Hecq, Jean-Henri; Goffart, Anne

    2011-08-01

    Ichthyoplankton samples were collected from 19 to 31 January 2004 in the Dumont d’Urville Sea (East Antarctic shelf). The Nototheniidae Pleuragramma antarcticum comprised more than 90% of the sampled larvae. Gut contents of 95 P antarcticum larvae were examined. Most larvae fed on phytoplankton, especially diatoms, whereas some other specimens had a mixed diet with phyto- and zooplankton prey. A single specimen fed exclusively on copepods. The stomach contents was dominated by three diatoms taxa, such as Thalassiothrix antarctica, Fragilariopsis spp. and Chaetoceros spp. Prey selection was apparently food density dependent, with an inverse relationship between food abundance and selection feeding. Larvae selected positively some diatoms, such as Coscinodiscus spp. and T. antarctica, presenting a low concentration in the water column compared to Fragilariopsis spp., which were strongly negatively selected. During summer, larvae were opportunistic feeders with a broad trophic niche, which allowed them to switch between different food types.

  8. Revised NEO Personality Inventory normative data for police officer selection.

    PubMed

    Detrick, Paul; Chibnall, John T

    2013-11-01

    The Revised NEO Personality Inventory (NEO PI-R) has demonstrated utility in the personnel selection context. Its use in police officer selection has been relatively limited, in part, because there are no published normative data for the NEO PI-R for police officer applicants. The authors present normative data on NEO PI-R domain and facet scores for a large sample (N = 288) of police officer applicants in a large, urban, Midwestern police department who completed the NEO PI-R as part of a preemployment psychological evaluation. Applicants reported low levels of Neuroticism and high levels of Extraversion and Conscientiousness. Neuroticism and Conscientiousness scores were strongly and consistently correlated with the Positive Presentation Management (PPM) research validity scale of the NEO PI-R. Extraversion and Agreeableness scores were moderately and less consistently correlated with PPM. These data may serve as a normative comparison group for professionals and researchers who use or may want to use the NEO PI-R in the police officer selection context.

  9. Socioemotional selectivity theory, aging, and health: the increasingly delicate balance between regulating emotions and making tough choices.

    PubMed

    Löckenhoff, Corinna E; Carstensen, Laura L

    2004-12-01

    After providing an introductory overview of socioemotional selectivity theory, we review empirical evidence for its basic postulates and consider the implications of the predicted cognitive and behavioral changes for physical health. The main assertion of socioemotional selectivity theory is that when boundaries on time are perceived, present-oriented goals related to emotional meaning are prioritized over future-oriented goals aimed at acquiring information and expanding horizons. Such motivational changes, which are strongly correlated with chronological age, systematically influence social preferences, social network composition, emotion regulation, and cognitive processing. On the one hand, there is considerable reason to believe that such changes are good for well-being and social adjustment. On the other hand, the very same motivational changes may limit health-related information-seeking and influence attention, memory, and decision-making such that positive material is favored over negative information. Grounding our arguments in socioemotional selectivity theory, we consider possible ways to tailor contexts such that disadvantages are avoided.

  10. Patterns and rates of intron divergence between humans and chimpanzees

    PubMed Central

    Gazave, Elodie; Marqués-Bonet, Tomàs; Fernando, Olga; Charlesworth, Brian; Navarro, Arcadi

    2007-01-01

    Background Introns, which constitute the largest fraction of eukaryotic genes and which had been considered to be neutral sequences, are increasingly acknowledged as having important functions. Several studies have investigated levels of evolutionary constraint along introns and across classes of introns of different length and location within genes. However, thus far these studies have yielded contradictory results. Results We present the first analysis of human-chimpanzee intron divergence, in which differences in the number of substitutions per intronic site (Ki) can be interpreted as the footprint of different intensities and directions of the pressures of natural selection. Our main findings are as follows: there was a strong positive correlation between intron length and divergence; there was a strong negative correlation between intron length and GC content; and divergence rates vary along introns and depending on their ordinal position within genes (for instance, first introns are more GC rich, longer and more divergent, and divergence is lower at the 3' and 5' ends of all types of introns). Conclusion We show that the higher divergence of first introns is related to their larger size. Also, the lower divergence of short introns suggests that they may harbor a relatively greater proportion of regulatory elements than long introns. Moreover, our results are consistent with the presence of functionally relevant sequences near the 5' and 3' ends of introns. Finally, our findings suggest that other parts of introns may also be under selective constraints. PMID:17309804

  11. [Secular trend of growth in stature in Florianópolis in the state of Santa Catarina (Brazil) in relation with the human development index (HDI)].

    PubMed

    Pinheiro, Andressa Caroline Carneiro; Niederauer, Juliana Minuzzi; Vargas, Deisi Maria

    2014-01-01

    The article seks to evaluate the secular trend of growth in stature of recruits in the 63rd Infantry Battalion in Florianópolis and correlate the information with the human development index (HDI). It involves a transversal and retrospective study of recruits aged between 18 and 20 who joined the 63rd IB in Florianópolis from 1963 to 2007. The sample comprised 600 individuals out of a total of 3000 recruits enlisted over the period. In each decade, three years were selected and within these years the first 40 files were systematically selected for analysis. It was seen that there was an increase in the order of 7 cm in height of recruits in Florianopolis over the past 47 years. This increase was more marked between the decades of 1990 and 2000, with the municipality of Blumenau having the highest average. The average heights study over the decades showed a strong positive correlation with the HDI of Florianopolis during the same period. When comparing the heights of the capital of Santa Catarina and previous studies in Blumenau, it was found that both cities have achieved the same increase of 1.4 cm/decade in the period between the 1960 and 2000. There was a positive secular trend in growth in Florianopolis, with a strong correlation with HDI values of the city between 1960 and 2000.

  12. Scientific Progress or Regress in Sports Physiology?

    PubMed

    Böning, Dieter

    2016-11-01

    In modern societies there is strong belief in scientific progress, but, unfortunately, a parallel partial regress occurs because of often avoidable mistakes. Mistakes are mainly forgetting, erroneous theories, errors in experiments and manuscripts, prejudice, selected publication of "positive" results, and fraud. An example of forgetting is that methods introduced decades ago are used without knowing the underlying theories: Basic articles are no longer read or cited. This omission may cause incorrect interpretation of results. For instance, false use of actual base excess instead of standard base excess for calculation of the number of hydrogen ions leaving the muscles raised the idea that an unknown fixed acid is produced in addition to lactic acid during exercise. An erroneous theory led to the conclusion that lactate is not the anion of a strong acid but a buffer. Mistakes occur after incorrect application of a method, after exclusion of unwelcome values, during evaluation of measurements by false calculations, or during preparation of manuscripts. Co-authors, as well as reviewers, do not always carefully read papers before publication. Peer reviewers might be biased against a hypothesis or an author. A general problem is selected publication of positive results. An example of fraud in sports medicine is the presence of doped subjects in groups of investigated athletes. To reduce regress, it is important that investigators search both original and recent articles on a topic and conscientiously examine the data. All co-authors and reviewers should read the text thoroughly and inspect all tables and figures in a manuscript.

  13. Between-Region Genetic Divergence Reflects the Mode and Tempo of Tumor Evolution

    PubMed Central

    Sun, Ruping; Hu, Zheng; Sottoriva, Andrea; Graham, Trevor A.; Harpak, Arbel; Ma, Zhicheng; Fischer, Jared M.; Shibata, Darryl; Curtis, Christina

    2017-01-01

    Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multi-region sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition. We developed a classifier based on measures of between-region subclonal genetic divergence and projected patient data into model space, revealing different modes of evolution both within and between solid tumor types. Our findings have broad implications for how human tumors progress, accumulate intra-tumor heterogeneity, and ultimately how they may be more effectively treated. PMID:28581503

  14. Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel

    PubMed Central

    Schmidt, Joshua M.; Battlay, Paul; Gledhill-Smith, Rebecca S.; Good, Robert T.; Lumb, Chris; Fournier-Level, Alexandre; Robin, Charles

    2017-01-01

    Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies (GWAS) to identify DDT-associated polygenes and use selective sweep analyses to assess their adaptive significance. We identify and verify two candidate DDT resistance loci. A largely uncharacterized gene, CG10737, has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1, shows compelling evidence of positive selection. PMID:28935691

  15. Prevalence of dental fluorosis in relation with different fluoride levels in drinking water among school going children in Sarada tehsil of Udaipur district, Rajasthan.

    PubMed

    Sarvaiya, B U; Bhayya, D; Arora, R; Mehta, D N

    2012-01-01

    To estimate the prevalence of dental fluorosis in relation with different fluoride levels in drinking water among school going children of 6-12 years age group. Dental fluorosis was recorded using Dean's index in school children of selected villages. The drinking water samples of all the selected villages were collected in polyethylene bottles and the fluoride content of these samples was determined by fluoride ion selective method using Orion microprocessor analyser. The overall prevalence of dental fluorosis was found to be 69.84%. An increase in the community fluorosis index (CFI) with corresponding increase in water fluoride content was found. There was an increase in prevalence of dental fluorosis with a corresponding increase in water fluoride content from 0.8 ppm to 4.1 ppm. A significantly strong positive correlation was found between CFI and fluoride concentration in drinking water.

  16. Disease-associated mitochondrial mutations and the evolution of primate mitogenomes

    PubMed Central

    Tavares, William Corrêa

    2017-01-01

    Several human diseases have been associated with mutations in mitochondrial genes comprising a set of confirmed and reported mutations according to the MITOMAP database. An analysis of complete mitogenomes across 139 primate species showed that most confirmed disease-associated mutations occurred in aligned codon positions and gene regions under strong purifying selection resulting in a strong evolutionary conservation. Only two confirmed variants (7.1%), coding for the same amino acids accounting for severe human diseases, were identified without apparent pathogenicity in non-human primates, like the closely related Bornean orangutan. Conversely, reported disease-associated mutations were not especially concentrated in conserved codon positions, and a large fraction of them occurred in highly variable ones. Additionally, 88 (45.8%) of reported mutations showed similar variants in several non-human primates and some of them have been present in extinct species of the genus Homo. Considering that recurrent mutations leading to persistent variants throughout the evolutionary diversification of primates are less likely to be severely damaging to fitness, we suggest that these 88 mutations are less likely to be pathogenic. Conversely, 69 (35.9%) of reported disease-associated mutations occurred in extremely conserved aligned codon positions which makes them more likely to damage the primate mitochondrial physiology. PMID:28510580

  17. Attitudes of Iranian infertile couples toward surrogacy

    PubMed Central

    Kian, Ensiyeh Mohebbi; Riazi, Hedieh; Bashirian, Saeid

    2014-01-01

    BACKGROUND: Surrogacy arrangements are multifaceted in nature, involving multiple controversial aspects and engaging ethical, moral, psychological and social issues. Successful treatment in reproductive medicine is strongly based on the mutual agreement of both partners, especially in Iran where men often make the final decision for health-related problems of this nature. AIM: The aim of the following study is to assess the attitudes of Iranian infertile couples toward surrogacy. SETTING AND DESIGN: This descriptive study was conducted at the infertility clinic of Hamadan university of medical sciences, Iran. MATERIALS AND METHODS: The study sample consisted of 150 infertile couples selected using a systematic randomized method. Data collection was based on responses to a questionnaire consisting of 22 questions. STATISTICAL ANALYSIS: P <0.05 were considered to be statistically significant. RESULTS: While 33.3% of men and 43.3% of women surveyed insisted on not using surrogacy, the overall attitudes toward surrogacy were positive (53.3% of women and 54.6% of men surveyed). CONCLUSION: Although, there was not a significant difference between the overall positive attitudes of infertile women and men toward surrogacy, the general attitude toward using this method is not strongly positive. Therefore, further efforts are required to increase the acceptability of surrogacy among infertile couples. PMID:24829531

  18. Selective attention to a facial feature with and without facial context: an ERP-study.

    PubMed

    Wijers, A A; Van Besouw, N J P; Mulder, G

    2002-04-01

    The present experiment addressed the question whether selectively attending to a facial feature (mouth shape) would benefit from the presence of a correct facial context. Subjects attended selectively to one of two possible mouth shapes belonging to photographs of a face with a happy or sad expression, respectively. These mouths were presented randomly either in isolation, embedded in the original photos, or in an exchanged facial context. The ERP effect of attending mouth shape was a lateral posterior negativity, anterior positivity with an onset latency of 160-200 ms; this effect was completely unaffected by the type of facial context. When the mouth shape and the facial context conflicted, this resulted in a medial parieto-occipital positivity with an onset latency of 180 ms, independent of the relevance of the mouth shape. Finally, there was a late (onset at approx. 400 ms) expression (happy vs. sad) effect, which was strongly lateralized to the right posterior hemisphere and was most prominent for attended stimuli in the correct facial context. For the isolated mouth stimuli, a similarly distributed expression effect was observed at an earlier latency range (180-240 ms). These data suggest the existence of separate, independent and neuroanatomically segregated processors engaged in the selective processing of facial features and the detection of contextual congruence and emotional expression of face stimuli. The data do not support that early selective attention processes benefit from top-down constraints provided by the correct facial context.

  19. Transport across the outer membrane porin of mycolic acid containing actinomycetales: Nocardia farcinica.

    PubMed

    Singh, Pratik Raj; Bajaj, Harsha; Benz, Roland; Winterhalter, Mathias; Mahendran, Kozhinjampara R

    2015-02-01

    The role of the outer-membrane channel from a mycolic acid containing Gram-positive bacteria Nocardia farcinica, which forms a hydrophilic pathway across the cell wall, was characterized. Single channel electrophysiology measurements and liposome swelling assays revealed the permeation of hydrophilic solutes including sugars, amino acids and antibiotics. The cation selective N. farcinica channel exhibited strong interaction with the positively charged antibiotics; amikacin and kanamycin, and surprisingly also with the negatively charged ertapenem. Voltage dependent kinetics of amikacin and kanamycin interactions were studied to distinguish binding from translocation. Moreover, the importance of charged residues inside the channel was investigated using mutational studies that revealed rate limiting interactions during the permeation. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Molecular evolution of the odorant and gustatory receptor genes in lepidopteran insects: implications for their adaptation and speciation.

    PubMed

    Engsontia, Patamarerk; Sangket, Unitsa; Chotigeat, Wilaiwan; Satasook, Chutamas

    2014-08-01

    Lepidoptera (comprised of butterflies and moths) is one of the largest groups of insects, including more than 160,000 described species. Chemoreception plays important roles in the adaptation of these species to a wide range of niches, e.g., plant hosts, egg-laying sites, and mates. This study investigated the molecular evolution of the lepidopteran odorant (Or) and gustatory receptor (Gr) genes using recently identified genes from Bombyx mori, Danaus plexippus, Heliconius melpomene, Plutella xylostella, Heliothis virescens, Manduca sexta, Cydia pomonella, and Spodoptera littoralis. A limited number of cases of large lineage-specific gene expansion are observed (except in the P. xylostella lineage), possibly due to selection against tandem gene duplication. There has been strong purifying selection during the evolution of both lepidopteran odorant and gustatory genes, as shown by the low ω values estimated through CodeML analysis, ranging from 0.0093 to 0.3926. However, purifying selection has been relaxed on some amino acid sites in these receptors, leading to sequence divergence, which is a precursor of positive selection on these sequences. Signatures of positive selection were detected only in a few loci from the lineage-specific analysis. Estimation of gene gains and losses suggests that the common ancestor of the Lepidoptera had fewer Or genes compared to extant species and an even more reduced number of Gr genes, particularly within the bitter receptor clade. Multiple gene gains and a few gene losses occurred during the evolution of Lepidoptera. Gene family expansion may be associated with the adaptation of lepidopteran species to plant hosts, especially after angiosperm radiation. Phylogenetic analysis of the moth sex pheromone receptor genes suggested that chromosomal translocations have occurred several times. New sex pheromone receptors have arisen through tandem gene duplication. Positive selection was detected at some amino acid sites predicted to be in the extracellular and transmembrane regions of the newly duplicated genes, which might be associated with the evolution of the new pheromone receptors.

  1. The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.

    PubMed

    Wu, Chung-I; Wang, Hurng-Yi; Ling, Shaoping; Lu, Xuemei

    2016-11-23

    Although tumorigenesis has been accepted as an evolutionary process ( 20 , 102 ), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms ( 20 , 29 ). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies ( 81 , 123 ). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.

  2. Hypoxia adaptations in the grey wolf (Canis lupus chanco) from Qinghai-Tibet Plateau.

    PubMed

    Zhang, Wenping; Fan, Zhenxin; Han, Eunjung; Hou, Rong; Zhang, Liang; Galaverni, Marco; Huang, Jie; Liu, Hong; Silva, Pedro; Li, Peng; Pollinger, John P; Du, Lianming; Zhang, XiuyYue; Yue, Bisong; Wayne, Robert K; Zhang, Zhihe

    2014-07-01

    The Tibetan grey wolf (Canis lupus chanco) occupies habitats on the Qinghai-Tibet Plateau, a high altitude (>3000 m) environment where low oxygen tension exerts unique selection pressure on individuals to adapt to hypoxic conditions. To identify genes involved in hypoxia adaptation, we generated complete genome sequences of nine Chinese wolves from high and low altitude populations at an average coverage of 25× coverage. We found that, beginning about 55,000 years ago, the highland Tibetan grey wolf suffered a more substantial population decline than lowland wolves. Positively selected hypoxia-related genes in highland wolves are enriched in the HIF signaling pathway (P = 1.57E-6), ATP binding (P = 5.62E-5), and response to an oxygen-containing compound (P≤5.30E-4). Of these positively selected hypoxia-related genes, three genes (EPAS1, ANGPT1, and RYR2) had at least one specific fixed non-synonymous SNP in highland wolves based on the nine genome data. Our re-sequencing studies on a large panel of individuals showed a frequency difference greater than 58% between highland and lowland wolves for these specific fixed non-synonymous SNPs and a high degree of LD surrounding the three genes, which imply strong selection. Past studies have shown that EPAS1 and ANGPT1 are important in the response to hypoxic stress, and RYR2 is involved in heart function. These three genes also exhibited significant signals of natural selection in high altitude human populations, which suggest similar evolutionary constraints on natural selection in wolves and humans of the Qinghai-Tibet Plateau.

  3. Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication.

    PubMed

    Montague, Michael J; Li, Gang; Gandolfi, Barbara; Khan, Razib; Aken, Bronwen L; Searle, Steven M J; Minx, Patrick; Hillier, LaDeana W; Koboldt, Daniel C; Davis, Brian W; Driscoll, Carlos A; Barr, Christina S; Blackistone, Kevin; Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas; Alkan, Can; Thomas, Gregg W C; Hahn, Matthew W; Menotti-Raymond, Marilyn; O'Brien, Stephen J; Wilson, Richard K; Lyons, Leslie A; Murphy, William J; Warren, Wesley C

    2014-12-02

    Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.

  4. Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

    PubMed Central

    Li, Gang; Gandolfi, Barbara; Khan, Razib; Aken, Bronwen L.; Searle, Steven M. J.; Minx, Patrick; Hillier, LaDeana W.; Koboldt, Daniel C.; Davis, Brian W.; Driscoll, Carlos A.; Barr, Christina S.; Blackistone, Kevin; Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas; Alkan, Can; Thomas, Gregg W. C.; Hahn, Matthew W.; Menotti-Raymond, Marilyn; O’Brien, Stephen J.; Wilson, Richard K.; Lyons, Leslie A.; Murphy, William J.; Warren, Wesley C.

    2014-01-01

    Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae. PMID:25385592

  5. Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

    PubMed

    Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

    2012-10-01

    Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  6. Female extrapair mating behavior can evolve via indirect selection on males

    PubMed Central

    Forstmeier, Wolfgang; Martin, Katrin; Bolund, Elisabeth; Schielzeth, Holger; Kempenaers, Bart

    2011-01-01

    In many species that form socially monogamous pair bonds, a considerable proportion of the offspring is sired by extrapair males. This observation has remained a puzzle for evolutionary biologists: although mating outside the pair bond can obviously increase the offspring production of males, the benefits of such behavior to females are less clear, yet females are known to actively solicit extrapair copulations. For more than two decades adaptionist explanations have dominated the discussions, yet remain controversial, and genetic constraint arguments have been dismissed without much consideration. An intriguing but still untested hypothesis states that extrapair mating behavior by females may be affected by the same genetic variants (alleles) as extrapair mating behavior by males, such that the female behavior could evolve through indirect selection on the male behavior. Here we show that in the socially monogamous zebra finch, individual differences in extrapair mating behavior have a hereditary component. Intriguingly, this genetic basis is shared between the sexes, as shown by a strong genetic correlation between male and female measurements of extrapair mating behavior. Hence, positive selection on males to sire extrapair young will lead to increased extrapair mating by females as a correlated evolutionary response. This behavior leads to a fundamentally different view of female extrapair mating: it may exist even if females obtain no net benefit from it, simply because the corresponding alleles were positively selected in the male ancestors. PMID:21670288

  7. Selective scanning tunnelling microscope electron-induced reactions of single biphenyl molecules on a Si(100) surface.

    PubMed

    Riedel, Damien; Bocquet, Marie-Laure; Lesnard, Hervé; Lastapis, Mathieu; Lorente, Nicolas; Sonnet, Philippe; Dujardin, Gérald

    2009-06-03

    Selective electron-induced reactions of individual biphenyl molecules adsorbed in their weakly chemisorbed configuration on a Si(100) surface are investigated by using the tip of a low-temperature (5 K) scanning tunnelling microscope (STM) as an atomic size source of electrons. Selected types of molecular reactions are produced, depending on the polarity of the surface voltage during STM excitation. At negative surface voltages, the biphenyl molecule diffuses across the surface in its weakly chemisorbed configuration. At positive surface voltages, different types of molecular reactions are activated, which involve the change of adsorption configuration from the weakly chemisorbed to the strongly chemisorbed bistable and quadristable configurations. Calculated reaction pathways of the molecular reactions on the silicon surface, using the nudge elastic band method, provide evidence that the observed selectivity as a function of the surface voltage polarity cannot be ascribed to different activation energies. These results, together with the measured threshold surface voltages and the calculated molecular electronic structures via density functional theory, suggest that the electron-induced molecular reactions are driven by selective electron detachment (oxidation) or attachment (reduction) processes.

  8. Genotypic character relationship and phenotypic path coefficient analysis in chili pepper genotypes grown under tropical condition.

    PubMed

    Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Oladosu, Yusuff; Kashiani, Pedram

    2017-03-01

    Studies on genotypic and phenotypic correlations among characters of crop plants are useful in planning, evaluating and setting selection criteria for the desired characters in a breeding program. The present study aimed to estimate the phenotypic correlation coefficients among yield and yield attributed characters and to work out the direct and indirect effects of yield-related characters on yield per plant using path coefficient analysis. Twenty-six genotypes of chili pepper were laid out in a randomized complete block design with three replications. Yield per plant showed positive and highly significant (P ≤ 0.01) correlations with most of the characters studied at both the phenotypic and genotypic levels. By contrast, disease incidence and days to flowering showed a significant negative association with yield. Fruit weight and number of fruits exerted positive direct effect on yield and also had a positive and significant (P ≤ 0.01) correlation with yield per plant. However, fruit length showed a low negative direct effect with a strong and positive indirect effect through fruit weight on yield and had a positive and significant association with yield. Longer fruits, heavy fruits and a high number of fruits are variables that are related to higher yields of chili pepper under tropical conditions and hence could be used as a reliable indicator in indirect selection for yield. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  9. A new method for selectively enhancing hemisphere processing: voice frequency amplification influences the strength of attribute framing.

    PubMed

    McCormick, Michael; Seta, John J

    2012-01-01

    An attribute framing effect occurs when positive or negative associations produced by positive or negative frames are mapped onto evaluations resulting in a more favourable evaluation for the positively framed attribute. We used a new voice frequency manipulation to differentially enhance right versus left hemisphere processing. In doing so we found a strong attribute framing effect when a speaker with a low-frequency voice enhanced the contextual processing style of the right hemisphere. However, a framing effect was not obtained when a speaker with a high-frequency voice enhanced the inferential/analytical processing style of the left hemisphere. At the theoretical level our results provide evidence that the contextual processing style of the right hemisphere is especially susceptible to associative implications, such as those found in attribute framing manipulations. At the applied level we provide a simple method for altering the effectiveness of persuasion messages.

  10. Enhanced Telecom Emission from Single Group-IV Quantum Dots by Precise CMOS-Compatible Positioning in Photonic Crystal Cavities.

    PubMed

    Schatzl, Magdalena; Hackl, Florian; Glaser, Martin; Rauter, Patrick; Brehm, Moritz; Spindlberger, Lukas; Simbula, Angelica; Galli, Matteo; Fromherz, Thomas; Schäffler, Friedrich

    2017-03-15

    Efficient coupling to integrated high-quality-factor cavities is crucial for the employment of germanium quantum dot (QD) emitters in future monolithic silicon-based optoelectronic platforms. We report on strongly enhanced emission from single Ge QDs into L3 photonic crystal resonator (PCR) modes based on precise positioning of these dots at the maximum of the respective mode field energy density. Perfect site control of Ge QDs grown on prepatterned silicon-on-insulator substrates was exploited to fabricate in one processing run almost 300 PCRs containing single QDs in systematically varying positions within the cavities. Extensive photoluminescence studies on this cavity chip enable a direct evaluation of the position-dependent coupling efficiency between single dots and selected cavity modes. The experimental results demonstrate the great potential of the approach allowing CMOS-compatible parallel fabrication of arrays of spatially matched dot/cavity systems for group-IV-based data transfer or quantum optical systems in the telecom regime.

  11. Enhanced Telecom Emission from Single Group-IV Quantum Dots by Precise CMOS-Compatible Positioning in Photonic Crystal Cavities

    PubMed Central

    2017-01-01

    Efficient coupling to integrated high-quality-factor cavities is crucial for the employment of germanium quantum dot (QD) emitters in future monolithic silicon-based optoelectronic platforms. We report on strongly enhanced emission from single Ge QDs into L3 photonic crystal resonator (PCR) modes based on precise positioning of these dots at the maximum of the respective mode field energy density. Perfect site control of Ge QDs grown on prepatterned silicon-on-insulator substrates was exploited to fabricate in one processing run almost 300 PCRs containing single QDs in systematically varying positions within the cavities. Extensive photoluminescence studies on this cavity chip enable a direct evaluation of the position-dependent coupling efficiency between single dots and selected cavity modes. The experimental results demonstrate the great potential of the approach allowing CMOS-compatible parallel fabrication of arrays of spatially matched dot/cavity systems for group-IV-based data transfer or quantum optical systems in the telecom regime. PMID:28345012

  12. Climate variability slows evolutionary responses of Colias butterflies to recent climate change.

    PubMed

    Kingsolver, Joel G; Buckley, Lauren B

    2015-03-07

    How does recent climate warming and climate variability alter fitness, phenotypic selection and evolution in natural populations? We combine biophysical, demographic and evolutionary models with recent climate data to address this question for the subalpine and alpine butterfly, Colias meadii, in the southern Rocky Mountains. We focus on predicting patterns of selection and evolution for a key thermoregulatory trait, melanin (solar absorptivity) on the posterior ventral hindwings, which affects patterns of body temperature, flight activity, adult and egg survival, and reproductive success in Colias. Both mean annual summer temperatures and thermal variability within summers have increased during the past 60 years at subalpine and alpine sites. At the subalpine site, predicted directional selection on wing absorptivity has shifted from generally positive (favouring increased wing melanin) to generally negative during the past 60 years, but there is substantial variation among years in the predicted magnitude and direction of selection and the optimal absorptivity. The predicted magnitude of directional selection at the alpine site declined during the past 60 years and varies substantially among years, but selection has generally been positive at this site. Predicted evolutionary responses to mean climate warming at the subalpine site since 1980 is small, because of the variability in selection and asymmetry of the fitness function. At both sites, the predicted effects of adaptive evolution on mean population fitness are much smaller than the fluctuations in mean fitness due to climate variability among years. Our analyses suggest that variation in climate within and among years may strongly limit evolutionary responses of ectotherms to mean climate warming in these habitats. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  13. Fast Evolution from Precast Bricks: Genomics of Young Freshwater Populations of Threespine Stickleback Gasterosteus aculeatus

    PubMed Central

    Terekhanova, Nadezhda V.; Logacheva, Maria D.; Penin, Aleksey A.; Neretina, Tatiana V.; Barmintseva, Anna E.; Bazykin, Georgii A.; Kondrashov, Alexey S.; Mugue, Nikolai S.

    2014-01-01

    Adaptation is driven by natural selection; however, many adaptations are caused by weak selection acting over large timescales, complicating its study. Therefore, it is rarely possible to study selection comprehensively in natural environments. The threespine stickleback (Gasterosteus aculeatus) is a well-studied model organism with a short generation time, small genome size, and many genetic and genomic tools available. Within this originally marine species, populations have recurrently adapted to freshwater all over its range. This evolution involved extensive parallelism: pre-existing alleles that adapt sticklebacks to freshwater habitats, but are also present at low frequencies in marine populations, have been recruited repeatedly. While a number of genomic regions responsible for this adaptation have been identified, the details of selection remain poorly understood. Using whole-genome resequencing, we compare pooled genomic samples from marine and freshwater populations of the White Sea basin, and identify 19 short genomic regions that are highly divergent between them, including three known inversions. 17 of these regions overlap protein-coding genes, including a number of genes with predicted functions that are relevant for adaptation to the freshwater environment. We then analyze four additional independently derived young freshwater populations of known ages, two natural and two artificially established, and use the observed shifts of allelic frequencies to estimate the strength of positive selection. Adaptation turns out to be quite rapid, indicating strong selection acting simultaneously at multiple regions of the genome, with selection coefficients of up to 0.27. High divergence between marine and freshwater genotypes, lack of reduction in polymorphism in regions responsible for adaptation, and high frequencies of freshwater alleles observed even in young freshwater populations are all consistent with rapid assembly of G. aculeatus freshwater genotypes from pre-existing genomic regions of adaptive variation, with strong selection that favors this assembly acting simultaneously at multiple loci. PMID:25299485

  14. Fast evolution from precast bricks: genomics of young freshwater populations of threespine stickleback Gasterosteus aculeatus.

    PubMed

    Terekhanova, Nadezhda V; Logacheva, Maria D; Penin, Aleksey A; Neretina, Tatiana V; Barmintseva, Anna E; Bazykin, Georgii A; Kondrashov, Alexey S; Mugue, Nikolai S

    2014-10-01

    Adaptation is driven by natural selection; however, many adaptations are caused by weak selection acting over large timescales, complicating its study. Therefore, it is rarely possible to study selection comprehensively in natural environments. The threespine stickleback (Gasterosteus aculeatus) is a well-studied model organism with a short generation time, small genome size, and many genetic and genomic tools available. Within this originally marine species, populations have recurrently adapted to freshwater all over its range. This evolution involved extensive parallelism: pre-existing alleles that adapt sticklebacks to freshwater habitats, but are also present at low frequencies in marine populations, have been recruited repeatedly. While a number of genomic regions responsible for this adaptation have been identified, the details of selection remain poorly understood. Using whole-genome resequencing, we compare pooled genomic samples from marine and freshwater populations of the White Sea basin, and identify 19 short genomic regions that are highly divergent between them, including three known inversions. 17 of these regions overlap protein-coding genes, including a number of genes with predicted functions that are relevant for adaptation to the freshwater environment. We then analyze four additional independently derived young freshwater populations of known ages, two natural and two artificially established, and use the observed shifts of allelic frequencies to estimate the strength of positive selection. Adaptation turns out to be quite rapid, indicating strong selection acting simultaneously at multiple regions of the genome, with selection coefficients of up to 0.27. High divergence between marine and freshwater genotypes, lack of reduction in polymorphism in regions responsible for adaptation, and high frequencies of freshwater alleles observed even in young freshwater populations are all consistent with rapid assembly of G. aculeatus freshwater genotypes from pre-existing genomic regions of adaptive variation, with strong selection that favors this assembly acting simultaneously at multiple loci.

  15. Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

    PubMed

    Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

    2013-12-01

    Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

  16. Sperm Competition Selects for Sperm Quantity and Quality in the Australian Maluridae

    PubMed Central

    Rowe, Melissah; Pruett-Jones, Stephen

    2011-01-01

    When ejaculates from rival males compete for fertilization, there is strong selection for sperm traits that enhance fertilization success. Sperm quantity is one such trait, and numerous studies have demonstrated a positive association between sperm competition and both testes size and the number of sperm available for copulations. Sperm competition is also thought to favor increases in sperm quality and changes in testicular morphology that lead to increased sperm production. However, in contrast to sperm quantity, these hypotheses have received considerably less empirical support and remain somewhat controversial. In a comparative study using the Australian Maluridae (fairy-wrens, emu-wrens, grasswrens), we tested whether increasing levels of sperm competition were associated with increases in both sperm quantity and quality, as well as an increase in the relative amount of seminiferous tubule tissue contained within the testes. After controlling for phylogeny, we found positive associations between sperm competition and sperm numbers, both in sperm reserves and in ejaculate samples. Additionally, as sperm competition level increased, the proportion of testicular spermatogenic tissue also increased, suggesting that sperm competition selects for greater sperm production per unit of testicular tissue. Finally, we also found that sperm competition level was positively associated with multiple sperm quality traits, including the proportion of motile sperm in ejaculates and the proportion of both viable and morphologically normal sperm in sperm reserves. These results suggest multiple ejaculate traits, as well as aspects of testicular morphology, have evolved in response to sperm competition in the Australian Maluridae. Furthermore, our findings emphasize the importance of post-copulatory sexual selection as an evolutionary force shaping macroevolutionary differences in sperm phenotype. PMID:21283577

  17. Genetic parameters for uniformity of harvest weight and body size traits in the GIFT strain of Nile tilapia.

    PubMed

    Marjanovic, Jovana; Mulder, Han A; Khaw, Hooi L; Bijma, Piter

    2016-06-10

    Animal breeding programs have been very successful in improving the mean levels of traits through selection. However, in recent decades, reducing the variability of trait levels between individuals has become a highly desirable objective. Reaching this objective through genetic selection requires that there is genetic variation in the variability of trait levels, a phenomenon known as genetic heterogeneity of environmental (residual) variance. The aim of our study was to investigate the potential for genetic improvement of uniformity of harvest weight and body size traits (length, depth, and width) in the genetically improved farmed tilapia (GIFT) strain. In order to quantify the genetic variation in uniformity of traits and estimate the genetic correlations between level and variance of the traits, double hierarchical generalized linear models were applied to individual trait values. Our results showed substantial genetic variation in uniformity of all analyzed traits, with genetic coefficients of variation for residual variance ranging from 39 to 58 %. Genetic correlation between trait level and variance was strongly positive for harvest weight (0.60 ± 0.09), moderate and positive for body depth (0.37 ± 0.13), but not significantly different from 0 for body length and width. Our results on the genetic variation in uniformity of harvest weight and body size traits show good prospects for the genetic improvement of uniformity in the GIFT strain. A high and positive genetic correlation was estimated between level and variance of harvest weight, which suggests that selection for heavier fish will also result in more variation in harvest weight. Simultaneous improvement of harvest weight and its uniformity will thus require index selection.

  18. Sperm competition selects for sperm quantity and quality in the Australian Maluridae.

    PubMed

    Rowe, Melissah; Pruett-Jones, Stephen

    2011-01-25

    When ejaculates from rival males compete for fertilization, there is strong selection for sperm traits that enhance fertilization success. Sperm quantity is one such trait, and numerous studies have demonstrated a positive association between sperm competition and both testes size and the number of sperm available for copulations. Sperm competition is also thought to favor increases in sperm quality and changes in testicular morphology that lead to increased sperm production. However, in contrast to sperm quantity, these hypotheses have received considerably less empirical support and remain somewhat controversial. In a comparative study using the Australian Maluridae (fairy-wrens, emu-wrens, grasswrens), we tested whether increasing levels of sperm competition were associated with increases in both sperm quantity and quality, as well as an increase in the relative amount of seminiferous tubule tissue contained within the testes. After controlling for phylogeny, we found positive associations between sperm competition and sperm numbers, both in sperm reserves and in ejaculate samples. Additionally, as sperm competition level increased, the proportion of testicular spermatogenic tissue also increased, suggesting that sperm competition selects for greater sperm production per unit of testicular tissue. Finally, we also found that sperm competition level was positively associated with multiple sperm quality traits, including the proportion of motile sperm in ejaculates and the proportion of both viable and morphologically normal sperm in sperm reserves. These results suggest multiple ejaculate traits, as well as aspects of testicular morphology, have evolved in response to sperm competition in the Australian Maluridae. Furthermore, our findings emphasize the importance of post-copulatory sexual selection as an evolutionary force shaping macroevolutionary differences in sperm phenotype.

  19. Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population.

    PubMed

    Bonnet, Timothée; Wandeler, Peter; Camenisch, Glauco; Postma, Erik

    2017-01-01

    In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called "stasis paradox" highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change.

  20. Bigger Is Fitter? Quantitative Genetic Decomposition of Selection Reveals an Adaptive Evolutionary Decline of Body Mass in a Wild Rodent Population

    PubMed Central

    Wandeler, Peter; Camenisch, Glauco

    2017-01-01

    In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called “stasis paradox” highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change. PMID:28125583

  1. SIMS of Organic Materials—Interface Location in Argon Gas Cluster Depth Profiles Using Negative Secondary Ions

    NASA Astrophysics Data System (ADS)

    Havelund, R.; Seah, M. P.; Tiddia, M.; Gilmore, I. S.

    2018-02-01

    A procedure has been established to define the interface position in depth profiles accurately when using secondary ion mass spectrometry and the negative secondary ions. The interface position varies strongly with the extent of the matrix effect and so depends on the secondary ion measured. Intensity profiles have been measured at both fluorenylmethyloxycarbonyl-uc(l)-pentafluorophenylalanine (FMOC) to Irganox 1010 and Irganox 1010 to FMOC interfaces for many secondary ions. These profiles show separations of the two interfaces that vary over some 10 nm depending on the secondary ion selected. The shapes of these profiles are strongly governed by matrix effects, slightly weakened by a long wavelength roughening. The matrix effects are separately measured using homogeneous, known mixtures of these two materials. Removal of the matrix and roughening effects give consistent compositional profiles for all ions that are described by an integrated exponentially modified Gaussian (EMG) profile. Use of a simple integrated Gaussian may lead to significant errors. The average interface positions in the compositional profiles are determined to standard uncertainties of 0.19 and 0.14 nm, respectively, using the integrated EMG function. Alternatively, and more simply, it is shown that interface positions and profiles may be deduced from data for several secondary ions with measured matrix factors by simply extrapolating the result to Ξ = 0. Care must be taken in quoting interface resolutions since those measured for predominantly Gaussian interfaces with Ξ above or below zero, without correction, appear significantly better than the true resolution.

  2. Relationships between avian richness and landscape structure at multiple scales using multiple landscapes

    USGS Publications Warehouse

    Mitchell, M.S.; Rutzmoser, S.H.; Wigley, T.B.; Loehle, C.; Gerwin, J.A.; Keyser, P.D.; Lancia, R.A.; Perry, R.W.; Reynolds, C.J.; Thill, R.E.; Weih, R.; White, D.; Wood, P.B.

    2006-01-01

    Little is known about factors that structure biodiversity on landscape scales, yet current land management protocols, such as forest certification programs, place an increasing emphasis on managing for sustainable biodiversity at landscape scales. We used a replicated landscape study to evaluate relationships between forest structure and avian diversity at both stand and landscape-levels. We used data on bird communities collected under comparable sampling protocols on four managed forests located across the Southeastern US to develop logistic regression models describing relationships between habitat factors and the distribution of overall richness and richness of selected guilds. Landscape models generated for eight of nine guilds showed a strong relationship between richness and both availability and configuration of landscape features. Diversity of topographic features and heterogeneity of forest structure were primary determinants of avian species richness. Forest heterogeneity, in both age and forest type, were strongly and positively associated with overall avian richness and richness for most guilds. Road density was associated positively but weakly with avian richness. Landscape variables dominated all models generated, but no consistent patterns in metrics or scale were evident. Model fit was strong for neotropical migrants and relatively weak for short-distance migrants and resident species. Our models provide a tool that will allow managers to evaluate and demonstrate quantitatively how management practices affect avian diversity on landscapes.

  3. Hypervariability of biofilm formation and oxacillin resistance in a Staphylococcus epidermidis strain causing persistent severe infection in an immunocompromised patient.

    PubMed

    Weisser, Maja; Schoenfelder, Sonja M K; Orasch, Christina; Arber, Caroline; Gratwohl, Alois; Frei, Reno; Eckart, Martin; Flückiger, Ursula; Ziebuhr, Wilma

    2010-07-01

    We report on a leukemic patient who suffered from a persistent, generalized, and eventually fatal Staphylococcus epidermidis infection during prolonged aplasia. Over a 6-week period, we isolated a genetically and phenotypically unstable S. epidermidis strain related to an epidemic clone associated with hospital infections worldwide. Strikingly, the strain showed a remarkable degree of variability, with evidence of selection and increasing predominance of biofilm-producing and oxacillin-resistant variants over time. Thus, in the early stages of the infection, the strain was found to generate subpopulations which had spontaneously lost the biofilm-mediating ica locus along with the oxacillin resistance-conferring mecA gene. These deletion mutants were obviously outcompeted by the ica- and mecA-positive wild-type genotype, with the selection and predominance of strongly biofilm-forming and oxacillin-resistant variants in the later stages of the infection. Also, a switch from protein- to polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG)-mediated-biofilm production was detected among ica-positive variants in the course of the infection. The data highlight the impact of distinct S. epidermidis clonal lineages as serious nosocomial pathogens that, through the generation and selection of highly pathogenic variants, may critically determine disease progression and outcome.

  4. Neural signals of selective attention are modulated by subjective preferences and buying decisions in a virtual shopping task.

    PubMed

    Goto, Nobuhiko; Mushtaq, Faisal; Shee, Dexter; Lim, Xue Li; Mortazavi, Matin; Watabe, Motoki; Schaefer, Alexandre

    2017-09-01

    We investigated whether well-known neural markers of selective attention to motivationally-relevant stimuli were modulated by variations in subjective preference towards consumer goods in a virtual shopping task. Specifically, participants viewed and rated pictures of various goods on the extent to which they wanted each item, which they could potentially purchase afterwards. Using the event-related potentials (ERP) method, we found that variations in subjective preferences for consumer goods strongly modulated positive slow waves (PSW) from 800 to 3000 milliseconds after stimulus onset. We also found that subjective preferences modulated the N200 and the late positive potential (LPP). In addition, we found that both PSW and LPP were modulated by subsequent buying decisions. Overall, these findings show that well-known brain event-related potentials reflecting selective attention processes can reliably index preferences to consumer goods in a shopping environment. Based on a large body of previous research, we suggest that early ERPs (e.g. the N200) to consumer goods could be indicative of preferences driven by unconditional and automatic processes, whereas later ERPs such as the LPP and the PSW could reflect preferences built upon more elaborative and conscious cognitive processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Egg-laying substrate selection for optimal camouflage by quail.

    PubMed

    Lovell, P George; Ruxton, Graeme D; Langridge, Keri V; Spencer, Karen A

    2013-02-04

    Camouflage is conferred by background matching and disruption, which are both affected by microhabitat. However, microhabitat selection that enhances camouflage has only been demonstrated in species with discrete phenotypic morphs. For most animals, phenotypic variation is continuous; here we explore whether such individuals can select microhabitats to best exploit camouflage. We use substrate selection in a ground-nesting bird (Japanese quail, Coturnix japonica). For such species, threat from visual predators is high and egg appearance shows strong between-female variation. In quail, variation in appearance is particularly obvious in the amount of dark maculation on the light-colored shell. When given a choice, birds consistently selected laying substrates that made visual detection of their egg outline most challenging. However, the strategy for maximizing camouflage varied with the degree of egg maculation. Females laying heavily maculated eggs selected the substrate that more closely matched egg maculation color properties, leading to camouflage through disruptive coloration. For lightly maculated eggs, females chose a substrate that best matched their egg background coloration, suggesting background matching. Our results show that quail "know" their individual egg patterning and seek out a nest position that provides most effective camouflage for their individual phenotype. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Microhabitat of small mammals at ground and understorey levels in a deciduous, southern Atlantic forest.

    PubMed

    Melo, Geruza L; Miotto, Barbara; Peres, Brisa; Cáceres, Nilton C

    2013-01-01

    Each animal species selects specific microhabitats for protection, foraging, or micro-climate. To understand the distribution patterns of small mammals on the ground and in the understorey, we investigated the use of microhabitats by small mammals in a deciduous forest of southern Brazil. Ten trap stations with seven capture points were used to sample the following microhabitats: liana, fallen log, ground litter, terrestrial ferns, simple-trunk tree, forked tree, and Piper sp. shrubs. Seven field phases were conducted, each for eight consecutive days, from September 2006 through January 2008. Four species of rodents (Akodon montensis, Sooretamys angouya, Oligoryzomys nigripes and Mus musculus) and two species of marsupials (Didelphis albiventris and Gracilinanus microtarsus) were captured. Captured species presented significant differences on their microhabitat use (ANOVA, p = 0.003), particularly between ground and understorey sites. Akodon montensis selected positively terrestrial ferns and trunks, S. angouya selected lianas, D. albiventris selected fallen trunks and Piper sp., and G. microtarsus choose tree trunks and lianas. We demonstrated that the local small-mammal assemblage does select microhabitats, with different types of associations between species and habitats. Besides, there is a strong evidence of habitat selection in order to diminish predation.

  7. Variation and evolution of male sex combs in Drosophila: nature of selection response and theories of genetic variation for sexual traits.

    PubMed

    Ahuja, Abha; Singh, Rama S

    2008-05-01

    We investigated the genetic architecture of variation in male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila. Twenty-four generations of divergent artificial selection for sex comb bristle number in a heterogeneous population of Drosophila melanogaster resulted in a significant response that was more pronounced in the direction of low bristle numbers. We observed a strong positive correlated response to selection in the corresponding female transverse bristle row. The correlated response in male abdominal and sternopleural bristle numbers, on the other hand, did not follow the same pattern as sex comb bristle number differences between selection lines. Relaxation-of-selection experiments along with mate choice and fecundity assays using the selection lines developed demonstrated the action of stabilizing selection on sex comb bristle number. Our results show (1) substantial genetic variation underlying sex comb bristle number variation; (2) a weak relationship between the sex comb and developmentally related, non-sex bristle systems; and (3) that sexual selection may be a driving force in sex comb evolution, indicating the potential of sex combs to diversify rapidly during population differentiation and speciation. We discuss the implications of these results for theories of genetic variation in display and nondisplay male sex traits.

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

    PubMed Central

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

    2014-01-01

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

  9. Continental-level population differentiation and environmental adaptation in the mushroom Suillus brevipes

    PubMed Central

    Branco, Sara; Bi, Ke; Liao, Hui-Ling; Gladieux, Pierre; Badouin, Hélène; Ellison, Christopher E.; Nguyen, Nhu H.; Vilgalys, Rytas; Peay, Kabir G.; Taylor, John W.; Bruns, Thomas D.

    2016-01-01

    Recent advancements in sequencing technology allowed researchers to better address the patterns and mechanisms involved in microbial environmental adaptation at large spatial scales. Here we investigated the genomic basis of adaptation to climate at the continental scale in Suillus brevipes, an ectomycorrhizal fungus symbiotically associated with the roots of pine trees. We used genomic data from 55 individuals in seven locations across North America to perform genome scans to detect signatures of positive selection and assess whether temperature and precipitation were associated with genetic differentiation. We found that S. brevipes exhibited overall strong population differentiation, with potential admixture in Canadian populations. This species also displayed genomic signatures of positive selection as well as genomic sites significantly associated with distinct climatic regimes and abiotic environmental parameters. These genomic regions included genes involved in transmembrane transport of substances and helicase activity potentially involved in cold stress response. Our study sheds light on large-scale environmental adaptation in fungi by identifying putative adaptive genes and providing a framework to further investigate the genetic basis of fungal adaptation. PMID:27761941

  10. Targeted Sos1 deletion reveals its critical role in early T-cell development

    PubMed Central

    Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Grinberg, Alex; Lee, Jan; Love, Paul E.; Samelson, Lawrence E.

    2011-01-01

    Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development. PMID:21746917

  11. Tetrel Bonding as a Vehicle for Strong and Selective Anion Binding.

    PubMed

    Scheiner, Steve

    2018-05-11

    Tetrel atoms T (T = Si, Ge, Sn, and Pb) can engage in very strong noncovalent interactions with nucleophiles, which are commonly referred to as tetrel bonds. The ability of such bonds to bind various anions is assessed with a goal of designing an optimal receptor. The Sn atom seems to form the strongest bonds within the tetrel family. It is most effective in the context of a -SnF₃ group and a further enhancement is observed when a positive charge is placed on the receptor. Connection of the -SnF₃ group to either an imidazolium or triazolium provides a strong halide receptor, which can be improved if its point of attachment is changed from the C to an N atom of either ring. Aromaticity of the ring offers no advantage nor is a cyclic system superior to a simple alkyl amine of any chain length. Placing a pair of -SnF₃ groups on a single molecule to form a bipodal dicationic receptor with two tetrel bonds enhances the binding, but falls short of a simple doubling. These two tetrel groups can be placed on opposite ends of an alkyl diamine chain of any length although SnF₃⁺NH₂(CH₂) n NH₂SnF₃⁺ with n between 2 and 4 seems to offer the strongest halide binding. Of the various anions tested, OH − binds most strongly: OH − > F − > Cl − > Br − > I − . The binding energy of the larger NO₃ − and HCO₃ − anions is more dependent upon the charge of the receptor. This pattern translates into very strong selectivity of binding one anion over another. The tetrel-bonding receptors bind far more strongly to each anion than an equivalent number of K⁺ counterions, which leads to equilibrium ratios in favor of the former of many orders of magnitude.

  12. Subangstrom resolution X-ray structure details aquaporin-water interactions.

    PubMed

    Eriksson, Urszula Kosinska; Fischer, Gerhard; Friemann, Rosmarie; Enkavi, Giray; Tajkhorshid, Emad; Neutze, Richard

    2013-06-14

    Aquaporins are membrane channels that facilitate the flow of water across biological membranes. Two conserved regions are central for selective function: the dual asparagine-proline-alanine (NPA) aquaporin signature motif and the aromatic and arginine selectivity filter (SF). Here, we present the crystal structure of a yeast aquaporin at 0.88 angstrom resolution. We visualize the H-bond donor interactions of the NPA motif's asparagine residues to passing water molecules; observe a polarized water-water H-bond configuration within the channel; assign the tautomeric states of the SF histidine and arginine residues; and observe four SF water positions too closely spaced to be simultaneously occupied. Strongly correlated movements break the connectivity of SF waters to other water molecules within the channel and prevent proton transport via a Grotthuss mechanism.

  13. The Evolution of Swift/BAT blazars and the origin of the MeV background

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ajello, M.; /SLAC /KIPAC, Menlo Park; Costamante, L.

    2009-10-17

    We use 3 years of data from the Swift/BAT survey to select a complete sample of X-ray blazars above 15 keV. This sample comprises 26 Flat-Spectrum Radio Quasars (FSRQs) and 12 BL Lac objects detected over a redshift range of 0.03 < z < 4.0. We use this sample to determine, for the first time in the 15-55 keV band, the evolution of blazars. We find that, contrary to the Seyfert-like AGNs detected by BAT, the population of blazars shows strong positive evolution. This evolution is comparable to the evolution of luminous optical QSOs and luminous X-ray selected AGNs. Wemore » also find evidence for an epoch-dependence of the evolution as determined previously for radio-quiet AGNs. We interpret both these findings as a strong link between accretion and jet activity. In our sample, the FSRQs evolve strongly, while our best-fit shows that BL Lacs might not evolve at all. The blazar population accounts for 10-20% (depending on the evolution of the BL Lacs) of the Cosmic X-ray background (CXB) in the 15-55 keV band. We find that FSRQs can explain the entire CXB emission for energies above 500 keV solving the mystery of the generation of the MeV background. The evolution of luminous FSRQs shows a peak in redshift (z{sub c} = 4.3 {+-} 0.5) which is larger than the one observed in QSOs and X-ray selected AGNs. We argue that FSRQs can be used as tracers of massive elliptical galaxies in the early Universe.« less

  14. Universal distribution of mutational effects on protein stability, uncoupling of protein robustness from sequence evolution and distinct evolutionary modes of prokaryotic and eukaryotic proteins

    NASA Astrophysics Data System (ADS)

    Faure, Guilhem; Koonin, Eugene V.

    2015-05-01

    Robustness to destabilizing effects of mutations is thought of as a key factor of protein evolution. The connections between two measures of robustness, the relative core size and the computationally estimated effect of mutations on protein stability (ΔΔG), protein abundance and the selection pressure on protein-coding genes (dN/dS) were analyzed for the organisms with a large number of available protein structures including four eukaryotes, two bacteria and one archaeon. The distribution of the effects of mutations in the core on protein stability is universal and indistinguishable in eukaryotes and bacteria, centered at slightly destabilizing amino acid replacements, and with a heavy tail of more strongly destabilizing replacements. The distribution of mutational effects in the hyperthermophilic archaeon Thermococcus gammatolerans is significantly shifted toward strongly destabilizing replacements which is indicative of stronger constraints that are imposed on proteins in hyperthermophiles. The median effect of mutations is strongly, positively correlated with the relative core size, in evidence of the congruence between the two measures of protein robustness. However, both measures show only limited correlations to the expression level and selection pressure on protein-coding genes. Thus, the degree of robustness reflected in the universal distribution of mutational effects appears to be a fundamental, ancient feature of globular protein folds whereas the observed variations are largely neutral and uncoupled from short term protein evolution. A weak anticorrelation between protein core size and selection pressure is observed only for surface residues in prokaryotes but a stronger anticorrelation is observed for all residues in eukaryotic proteins. This substantial difference between proteins of prokaryotes and eukaryotes is likely to stem from the demonstrable higher compactness of prokaryotic proteins.

  15. Genetic conflict between sexual signalling and juvenile survival in the three-spined stickleback.

    PubMed

    Kim, Sin-Yeon; Velando, Alberto

    2016-02-29

    Secondary sexual traits and mating preferences may evolve in part because the offspring of attractive males inherit attractiveness and other genetically correlated traits such as fecundity and viability. A problem regarding these indirect genetic mechanisms is how sufficient genetic variation in the traits subject to sexual selection is maintained within a population. Here we explored the additive genetic correlations between carotenoid-based male ornament colouration, female fecundity and juvenile survival rate in the three-spined stickleback (Gasterosteus aculeatus) to test the possibility that attractiveness genes reduce important fitness components in the bearers not expressing the sexual trait. Male sexual attractiveness (i.e., red nuptial colouration) as well as female fecundity and juvenile viability showed heritable variations in the three-spined stickleback. Thus, females can gain indirect benefits by mating with an attractive male. There was a strong positive genetic correlation between female fecundity and juvenile viability. However, red sexual signal of male sticklebacks was negatively genetically correlated with juvenile survival, suggesting genetic conflict between attractiveness and viability. There was no significant correlation between attractiveness of brothers and fecundity of sisters, suggesting no intra-locus sexual conflict. The negative effects of mating with a colourful male on offspring viability may contribute to maintaining the heritable variation under strong directional sexual selection. The strength of indirect sexual selection may be weaker than previously thought due to the hidden genetic conflicts.

  16. Convergent Evolution Associated with Habitat Decouples Phenotype from Phylogeny in a Clade of Lizards

    PubMed Central

    Edwards, Shelley; Vanhooydonck, Bieke; Herrel, Anthony; Measey, G. John; Tolley, Krystal A.

    2012-01-01

    Convergent evolution can explain similarity in morphology between species, due to selection on a fitness-enhancing phenotype in response to local environmental conditions. As selective pressures on body morphology may be strong, these have confounded our understanding of the evolutionary relationships between species. Within the speciose African radiation of lacertid lizards (Eremiadini), some species occupy a narrow habitat range (e.g. open habitat, cluttered habitat, strictly rupicolous, or strictly psammophilic), which may exert strong selective pressures on lizard body morphology. Here we show that the overall body plan is unrelated to shared ancestry in the African radiation of Eremiadini, but is instead coupled to habitat use. Comprehensive Bayesian and likelihood phylogenies using multiple representatives from all genera (2 nuclear, 2 mitochondrial markers) show that morphologically convergent species thought to represent sister taxa within the same genus are distantly related evolutionary lineages (Ichnotropis squamulosa and Ichnotropis spp.; Australolacerta rupicola and A. australis). Hierarchical clustering and multivariate analysis of morphological characters suggest that body, and head, width and height (stockiness), all of which are ecologically relevant with respect to movement through habitat, are similar between the genetically distant species. Our data show that convergence in morphology, due to adaptation to similar environments, has confounded the assignment of species leading to misidentification of the taxonomic position of I. squamulosa and the Australolacerta species. PMID:23251601

  17. [Profile of adolescents with repeated pregnancies attended at a prenatal clinic].

    PubMed

    Persona, Lia; Shimo, Antonieta Keiko Kakuda; Tarallo, Maria Celina

    2004-01-01

    This study identified the biopsychosocial profile of adolescent with repeated pregnancies, who were attended at a prenatal clinic. Data were collected through patient records and interviews and were subject to quantitative analysis. Based on the obtained results and in accordance with literature, factors that are strongly associated with the occurrence of pregnancy repetition were selected in the adolescents' profiles. These are: early menarche; first sexual intercourse shortly after menarche; school repetition; school dropout; non remunerated occupation; low family income; involvement with older partners; living with the partner; consensual union with the partner; one partner; low condom use; family history of adolescent pregnancy; father's absence because of death or abandonment; positive family reaction to previous pregnancy; previous abortion; adolescent's positive concepts about previous delivery; and absence from previous postpartum consultations.

  18. De Facto Versus de Jure Political Institutions in the Long-Run: A Multivariate Analysis, 1820-2000.

    PubMed

    Foldvari, Peter

    2017-01-01

    In this paper we use the components of the PolityIV project's polity2 and Vanhanen's Index of Democracy indicators to analyse the relationship between de jure and de facto political institutions from 1820 until 2000 with a canonical correlation method corrected for the sample selection bias. We find considerable fluctuation in the relationship between the two measures. After a moderate positive correlation found during the first half of the nineteenth century, the two measures become statistically unrelated until the 1940s. The relationship becomes strong and positive only in the second half of the twentieth century. The relationship between de jure and de facto political institutions hence can be described as a U-curve, reminiscent to an inverse Kuznets-curve.

  19. Differential expression of c-fos following administration of two tremorgenic agents: harmaline and oxotremorine.

    PubMed

    Miwa, H; Nishi, K; Fuwa, T; Mizuno, Y

    2000-08-03

    The regional distribution of c-Fos expression in the brain after the administration of two tremorgenic agents was studied. In both the harmaline- and oxotremorin-treated rats, c-Fos-positive neurons were extensively distributed in the basal ganglia nuclei and the cerebellum. Additionally, in the harmaline-treated rats, numerous c-Fos-positive neurons were also distributed throughout the inferior olivary nucleus. In the oxotremorine-treated rats, while the inferior olive was not involved, c-Fos was strongly expressed in the neurons of the reticular thalamic nucleus, possibly due to the muscarinic effects of oxotremorine. The present study revealed that the inferior olive is selectively activated in the harmaline-administered animals and that the basal ganglia are involved in both harmaline- and oxotremorine-induced tremors.

  20. The Effects of Context, Meaning Frequency, and Associative Strength on Semantic Selection: Distinct Contributions from each Cerebral Hemisphere

    PubMed Central

    Meyer, Aaron M.; Federmeier, Kara D.

    2008-01-01

    The visual half-field procedure was used to examine hemispheric asymmetries in meaning selection. Event-related potentials were recorded as participants decided if a lateralized ambiguous or unambiguous prime was related in meaning to a centrally-presented target. Prime-target pairs were preceded by a related or unrelated centrally-presented context word. To separate the effects of meaning frequency and associative strength, unambiguous words were paired with concordant weakly-related context words and strongly-related targets (e.g., taste-sweet-candy) that were similar in associative strength to discordant subordinate-related context words and dominant-related targets (e.g., river-bank-deposit) in the ambiguous condition. Context words and targets were reversed in a second experiment. In an unrelated (neutral) context, N400 responses were more positive than baseline (facilitated) in all ambiguous conditions except when subordinate targets were presented on left visual field-right hemisphere (LVF-RH) trials. Thus, in the absence of biasing context information, the hemispheres seem to be differentially affected by meaning frequency, with the left maintaining multiple meanings and the right selecting the dominant meaning. In the presence of discordant context information, N400 facilitation was absent in both visual fields, indicating that the contextually-consistent meaning of the ambiguous word had been selected. In contrast, N400 facilitation occurred in all of the unambiguous conditions; however, the left hemisphere (LH) showed less facilitation for the weakly-related target when a strongly-related context was presented. These findings indicate that both hemispheres use context to guide meaning selection, but that the LH is more likely to focus activation on a single, contextually-relevant sense. PMID:17936727

  1. The Chemical Basis for the Origin of the Genetic Code and the Process of Protein Synthesis

    NASA Technical Reports Server (NTRS)

    Lacey, James C., Jr.

    1990-01-01

    A model for the origin of protein synthesis. The essential features of the model are that 5'-AMP and perhaps other monoribonucleotides can serve as catalysts for the selective synthesis of L-based peptides. A unique set of characteristics of 5'-AMP is responsible for the selective catalysts and these characteristics are described in detail. The model involves the formation of diesters as intermediates and selectivity for use of the L-isomer occurs principally at the step of forming the diester. However, in the formation of acetyl phenylalanine-AMP monoester there is a selectivity for esterification by the D-isomer. Data showing this selectivity is presented. This selectivity for D-isomer disappears after the first step. The identity was confirmed of all four of possible diesters of acetyl-D- and -L phenylaline with 5'-AMP by nuclear magnetic resonance (NMR). The data using flourescence and NMR show the Trp ring can associate with the adenine ring more strongly when the D-isomer is in the 2' position than it can when in the 3' position. These same data also suggest a molecular mechanisim for the faster esterificaton of 5'-AMP by acetyl-D-phenylaline. Some new data is also presented on the possible structure of the 2' isomer of acetyl-D-tryptophan-AMP monoester. The HPLC elution times of all four possible acetyl diphenylalanine esters of 5'-AMP were studied, these peptidyl esters will be products in the studies of peptide formation on the ribose of 5'-AMP. Other studies were on the rate of synthesis and the identity of the product when producing 3'Ac-Phe-2'tBOC-Phe-AMP diester. HPLC purification and identification of this product were accomplished.

  2. Purifying selection and genetic drift shaped Pleistocene evolution of the mitochondrial genome in an endangered Australian freshwater fish.

    PubMed

    Pavlova, A; Gan, H M; Lee, Y P; Austin, C M; Gilligan, D M; Lintermans, M; Sunnucks, P

    2017-05-01

    Genetic variation in mitochondrial genes could underlie metabolic adaptations because mitochondrially encoded proteins are directly involved in a pathway supplying energy to metabolism. Macquarie perch from river basins exposed to different climates differ in size and growth rate, suggesting potential presence of adaptive metabolic differences. We used complete mitochondrial genome sequences to build a phylogeny, estimate lineage divergence times and identify signatures of purifying and positive selection acting on mitochondrial genes for 25 Macquarie perch from three basins: Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and Shoalhaven Basin (SB). Phylogenetic analysis resolved basin-level clades, supporting incipient speciation previously inferred from differentiation in allozymes, microsatellites and mitochondrial control region. The estimated time of lineage divergence suggested an early- to mid-Pleistocene split between SB and the common ancestor of HNB+MDB, followed by mid-to-late Pleistocene splitting between HNB and MDB. These divergence estimates are more recent than previous ones. Our analyses suggested that evolutionary drivers differed between inland MDB and coastal HNB. In the cooler and more climatically variable MDB, mitogenomes evolved under strong purifying selection, whereas in the warmer and more climatically stable HNB, purifying selection was relaxed. Evidence for relaxed selection in the HNB includes elevated transfer RNA and 16S ribosomal RNA polymorphism, presence of potentially mildly deleterious mutations and a codon (ATP6 113 ) displaying signatures of positive selection (ratio of nonsynonymous to synonymous substitution rates (dN/dS) >1, radical change of an amino-acid property and phylogenetic conservation across the Percichthyidae). In addition, the difference could be because of stronger genetic drift in the smaller and historically more subdivided HNB with low per-population effective population sizes.

  3. Finding strong lenses in CFHTLS using convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Jacobs, C.; Glazebrook, K.; Collett, T.; More, A.; McCarthy, C.

    2017-10-01

    We train and apply convolutional neural networks, a machine learning technique developed to learn from and classify image data, to Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) imaging for the identification of potential strong lensing systems. An ensemble of four convolutional neural networks was trained on images of simulated galaxy-galaxy lenses. The training sets consisted of a total of 62 406 simulated lenses and 64 673 non-lens negative examples generated with two different methodologies. An ensemble of trained networks was applied to all of the 171 deg2 of the CFHTLS wide field image data, identifying 18 861 candidates including 63 known and 139 other potential lens candidates. A second search of 1.4 million early-type galaxies selected from the survey catalogue as potential deflectors, identified 2465 candidates including 117 previously known lens candidates, 29 confirmed lenses/high-quality lens candidates, 266 novel probable or potential lenses and 2097 candidates we classify as false positives. For the catalogue-based search we estimate a completeness of 21-28 per cent with respect to detectable lenses and a purity of 15 per cent, with a false-positive rate of 1 in 671 images tested. We predict a human astronomer reviewing candidates produced by the system would identify 20 probable lenses and 100 possible lenses per hour in a sample selected by the robot. Convolutional neural networks are therefore a promising tool for use in the search for lenses in current and forthcoming surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope.

  4. The moderating effects of school climate on bullying prevention efforts.

    PubMed

    Low, Sabina; Van Ryzin, Mark

    2014-09-01

    Bullying prevention efforts have yielded mixed effects over the last 20 years. Program effectiveness is driven by a number of factors (e.g., program elements and implementation), but there remains a dearth of understanding regarding the role of school climate on the impact of bullying prevention programs. This gap is surprising, given research suggesting that bullying problems and climate are strongly related. The current study examines the moderating role of school climate on the impacts of a stand-alone bullying prevention curriculum. In addition, the current study examined 2 different dimensions of school climate across both student and staff perceptions. Data for this study were derived from a Steps to Respect (STR) randomized efficacy trial that was conducted in 33 elementary schools over a 1-year period. Schools were randomly assigned to intervention or wait-listed control condition. Outcome measures (pre-to-post) were obtained from (a) all school staff, (b) a randomly selected subset of 3rd-5th grade teachers in each school, and (c) all students in classrooms of selected teachers. Multilevel analyses revealed that psychosocial climate was strongly related to reductions in bullying-related attitudes and behaviors. Intervention status yielded only 1 significant main effect, although, STR schools with positive psychosocial climate at baseline had less victimization at posttest. Policies/administrative commitment to bullying were related to reduced perpetration among all schools. Findings suggest positive psychosocial climate (from both staff and student perspective) plays a foundational role in bullying prevention, and can optimize effects of stand-alone programs. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  5. Quantitative genetics of age at reproduction in wild swans: Support for antagonistic pleiotropy models of senescence

    PubMed Central

    Charmantier, Anne; Perrins, Christopher; McCleery, Robin H.; Sheldon, Ben C.

    2006-01-01

    Why do individuals stop reproducing after a certain age, and how is this age determined? The antagonistic pleiotropy theory for the evolution of senescence predicts that increased early-life performance should be accompanied by earlier (or faster) senescence. Hence, an individual that has started to breed early should also lose its reproductive capacities early. We investigate here the relationship between age at first reproduction (AFR) and age at last reproduction (ALR) in a free-ranging mute swan (Cygnus olor) population monitored for 36 years. Using multivariate analyses on the longitudinal data, we show that both traits are strongly selected in opposite directions. Analysis of the phenotypic covariance between these characters shows that individuals vary in their inherent quality, such that some individuals have earlier AFR and later ALR than expected. Quantitative genetic pedigree analyses show that both traits possess additive genetic variance but also that AFR and ALR are positively genetically correlated. Hence, although both traits display heritable variation and are under opposing directional selection, their evolution is constrained by a strong evolutionary tradeoff. These results are consistent with the theory that increased early-life performance comes with faster senescence because of genetic tradeoffs. PMID:16618935

  6. The strengths of r- and K-selection shape diversity-disturbance relationships.

    PubMed

    Bohn, Kristin; Pavlick, Ryan; Reu, Björn; Kleidon, Axel

    2014-01-01

    Disturbance is a key factor shaping species abundance and diversity in plant communities. Here, we use a mechanistic model of vegetation diversity to show that different strengths of r- and K-selection result in different disturbance-diversity relationships. R- and K-selection constrain the range of viable species through the colonization-competition tradeoff, with strong r-selection favoring colonizers and strong K-selection favoring competitors, but the level of disturbance also affects the success of species. This interplay among r- and K-selection and disturbance results in different shapes of disturbance-diversity relationships, with little variation of diversity with no r- and no K-selection, a decrease in diversity with r-selection with disturbance rate, an increase in diversity with K-selection, and a peak at intermediate values with strong r- and K-selection. We conclude that different disturbance-diversity relationships found in observations may reflect different intensities of r- and K-selection within communities, which should be inferable from broader observations of community composition and their ecophysiological trait ranges.

  7. Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in wild rodents (MURINAE)

    PubMed Central

    2013-01-01

    Background In vertebrates, it has been repeatedly demonstrated that genes encoding proteins involved in pathogen-recognition by adaptive immunity (e.g. MHC) are subject to intensive diversifying selection. On the other hand, the role and the type of selection processes shaping the evolution of innate-immunity genes are currently far less clear. In this study we analysed the natural variation and the evolutionary processes acting on two genes involved in the innate-immunity recognition of Microbe-Associated Molecular Patterns (MAMPs). Results We sequenced genes encoding Toll-like receptor 4 (Tlr4) and 7 (Tlr7), two of the key bacterial- and viral-sensing receptors of innate immunity, across 23 species within the subfamily Murinae. Although we have shown that the phylogeny of both Tlr genes is largely congruent with the phylogeny of rodents based on a comparably sized non-immune sequence dataset, we also identified several potentially important discrepancies. The sequence analyses revealed that major parts of both Tlrs are evolving under strong purifying selection, likely due to functional constraints. Yet, also several signatures of positive selection have been found in both genes, with more intense signal in the bacterial-sensing Tlr4 than in the viral-sensing Tlr7. 92% and 100% of sites evolving under positive selection in Tlr4 and Tlr7, respectively, were located in the extracellular domain. Directly in the Ligand-Binding Region (LBR) of TLR4 we identified two rapidly evolving amino acid residues and one site under positive selection, all three likely involved in species-specific recognition of lipopolysaccharide of gram-negative bacteria. In contrast, all putative sites of LBRTLR7 involved in the detection of viral nucleic acids were highly conserved across rodents. Interspecific differences in the predicted 3D-structure of the LBR of both Tlrs were not related to phylogenetic history, while analyses of protein charges clearly discriminated Rattini and Murini clades. Conclusions In consequence of the constraints given by the receptor protein function purifying selection has been a dominant force in evolution of Tlrs. Nevertheless, our results show that episodic diversifying parasite-mediated selection has shaped the present species-specific variability in rodent Tlrs. The intensity of diversifying selection was higher in Tlr4 than in Tlr7, presumably due to structural properties of their ligands. PMID:24028551

  8. HPV Integration in HNSCC Correlates with Survival Outcomes, Immune Response Signatures, and Candidate Drivers.

    PubMed

    Koneva, Lada A; Zhang, Yanxiao; Virani, Shama; Hall, Pelle B; McHugh, Jonathan B; Chepeha, Douglas B; Wolf, Gregory T; Carey, Thomas E; Rozek, Laura S; Sartor, Maureen A

    2018-01-01

    The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV + HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors ( n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1) A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV - patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4 + , CD3 + , regulatory, CD8 + T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90-102. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Opposing selection and environmental variation modify optimal timing of breeding.

    PubMed

    Tarwater, Corey E; Beissinger, Steven R

    2013-09-17

    Studies of evolution in wild populations often find that the heritable phenotypic traits of individuals producing the most offspring do not increase proportionally in the population. This paradox may arise when phenotypic traits influence both fecundity and viability and when there is a tradeoff between these fitness components, leading to opposing selection. Such tradeoffs are the foundation of life history theory, but they are rarely investigated in selection studies. Timing of breeding is a classic example of a heritable trait under directional selection that does not result in an evolutionary response. Using a 22-y study of a tropical parrot, we show that opposing viability and fecundity selection on the timing of breeding is common and affects optimal breeding date, defined by maximization of fitness. After accounting for sampling error, the directions of viability (positive) and fecundity (negative) selection were consistent, but the magnitude of selection fluctuated among years. Environmental conditions (rainfall and breeding density) primarily and breeding experience secondarily modified selection, shifting optimal timing among individuals and years. In contrast to other studies, viability selection was as strong as fecundity selection, late-born juveniles had greater survival than early-born juveniles, and breeding later in the year increased fitness under opposing selection. Our findings provide support for life history tradeoffs influencing selection on phenotypic traits, highlight the need to unify selection and life history theory, and illustrate the importance of monitoring survival as well as reproduction for understanding phenological responses to climate change.

  10. Drought survival and reproduction impose contrasting selection pressures on maximum body size and sexual size dimorphism in a snake, Seminatrix pygaea.

    PubMed

    Winne, Christopher T; Willson, John D; Whitfield Gibbons, J

    2010-04-01

    The causes and consequences of body size and sexual size dimorphism (SSD) have been central questions in evolutionary ecology. Two, often opposing selective forces are suspected to act on body size in animals: survival selection and reproductive (fecundity and sexual) selection. We have recently identified a system where a small aquatic snake species (Seminatrix pygaea) is capable of surviving severe droughts by aestivating within dried, isolated wetlands. We tested the hypothesis that the lack of aquatic prey during severe droughts would impose significant survivorship pressures on S. pygaea, and that the largest individuals, particularly females, would be most adversely affected by resource limitation. Our findings suggest that both sexes experience selection against large body size during severe drought when prey resources are limited, as nearly all S. pygaea are absent from the largest size classes and maximum body size and SSD are dramatically reduced following drought. Conversely, strong positive correlations between maternal body size and reproductive success in S. pygaea suggest that females experience fecundity selection for large size during non-drought years. Collectively, our study emphasizes the dynamic interplay between selection pressures that act on body size and supports theoretical predictions about the relationship between body size and survivorship in ectotherms under conditions of resource limitation.

  11. Has the phase-out of PBDEs affected their atmospheric levels? Trends of PBDEs and their replacements in the Great Lakes atmosphere.

    PubMed

    Ma, Yuning; Salamova, Amina; Venier, Marta; Hites, Ronald A

    2013-10-15

    Air and precipitation samples were collected every 12 days at five sites near the North American Great Lakes from 2005 to 2011 (inclusive) by the Integrated Atmospheric Deposition Network (IADN). The concentrations of polybrominated diphenyl ethers (PBDEs) and selected alternative brominated flame retardants [pentabromoethyl benzene (PBEB), hexabromobenzene (HBB), 1,2-bis(2,4,6-tribromophenoxy)ethane (TBE or BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), and bis(2-ethylhexyl)-tetrabromo-phthalate (TBPH)] were measured in these samples. The concentrations of almost all of these flame retardants were related to the number of people within a 25 km radius of the sampling site, except for HBB, the concentrations of which were relatively high at Sturgeon Point, and PBEB, the concentrations of which were relatively high at Eagle Harbor. The temporal trends of all of these concentrations were variable. For example, BDE-47 vapor phase concentrations were increasing with doubling times of 5-10 years at Sturgeon Point, Sleeping Bear Dunes, and Eagle Harbor, but these concentrations were slowly decreasing in all phases at Chicago. The most consistent trend was for TBE, which showed concentrations that were unchanging or decreasing in all phases at all sites. TBPH concentrations in particles and HBB concentrations in precipitation were rapidly increasing at most sites with doubling times of ~2 years. The concentrations of DBDPE and BDE-209 were strongly and positively correlated, and the concentrations of TBB and TBPH were also strongly and positively correlated. The concentrations of TBB plus TBPH (representing Firemaster 550) and BDE-47, 85, 99, 100, 153, plus 154 (representing the withdrawn penta-BDE commercial mixture) were also strongly and positively correlated. These positive relationships indicate that the replacement of the deca-BDE commercial product by DBDPE and the penta-BDE product by Firemaster 550 have not yet become evident in the Great Lakes' atmospheric environment.

  12. Influence of Strong versus Weak Fair Employment Policies and Applicant's Sex on Selection Decisions and Salary Recommendations in a Management Simulation.

    ERIC Educational Resources Information Center

    Rosen, Benson; Mericle, Mary F.

    1979-01-01

    Strong and weak policies on fair employment were equally effective in counteracting sex bias in selection decisions; however, lower starting salaries were recommended for females compared to males in the strong fair employment policy condition. (Author/IRT)

  13. Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

    PubMed Central

    2014-01-01

    Background Genes associated with the neurodevelopmental disorder microcephaly display a strong signature of adaptive evolution in primates. Comparative data suggest a link between selection on some of these loci and the evolution of primate brain size. Whether or not either positive selection or this phenotypic association are unique to primates is unclear, but recent studies in cetaceans suggest at least two microcephaly genes evolved adaptively in other large brained mammalian clades. Results Here we analyse the evolution of seven microcephaly loci, including three recently identified loci, across 33 eutherian mammals. We find extensive evidence for positive selection having acted on the majority of these loci not just in primates but also across non-primate mammals. Furthermore, the patterns of selection in major mammalian clades are not significantly different. Using phylogenetically corrected comparative analyses, we find that the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with neonatal brain size in Glires and Euungulata, the two most densely sampled non-primate clades. Conclusions Together with previous results, this suggests that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals. Nevertheless, several limitations of currently available data and gene-phenotype tests are discussed, including sparse sampling across large evolutionary distances, averaging gene-wide rates of evolution, potential phenotypic variation and evolutionary reversals. We discuss the implications of our results for studies of the genetic basis of brain evolution, and explicit tests of gene-phenotype hypotheses. PMID:24898820

  14. Convergent Evolution of Human-Isolated H7N9 Avian Influenza A Viruses.

    PubMed

    Xiang, Dan; Shen, Xuejuan; Pu, Zhiqing; Irwin, David M; Liao, Ming; Shen, Yongyi

    2018-05-05

    Avian influenza A virus H7N9 has caused 5 epidemic waves of human infections in China since 2013. Avian influenza A viruses may face strong selection to adapt to novel conditions when establishing themselves in humans. In this study, we sought to determine whether adaptive evolution had occurred in human-isolated H7N9 viruses. We evaluated all available genomes of H7N9 avian influenza A virus. Maximum likelihood trees were separately reconstructed for all 8 genes. Signals of positive selection and convergent evolution were then detected on branches that lead to changes in host tropism (from avian to human). We found that 3 genes had significant signals of positive selection (all of them P < .05). In addition, we detected 34 sites having significant signals for parallel evolution in 8 genes (all of them P < .05), including 7 well-known sites (Q591K, E627K, and D701N in PB2 gene; R156K, V202A, and L244Q in HA; and R289K in NA) that play roles in crossing species barriers for avian influenza A viruses. Our study suggests that, during infection in humans, H7N9 viruses have undergone adaptive evolution to adapt to their new host environment and that the sites where parallel evolution occurred might play roles in crossing species barriers and respond to the new selection pressures arising from their new host environments.

  15. SEXUAL SELECTION THROUGH FEMALE CHOICE IN LAWES' PAROTIA, A LEK-MATING BIRD OF PARADISE.

    PubMed

    Pruett-Jones, S G; Pruett-Jones, M A

    1990-05-01

    We studied sexual selection in Lawes' Parotia, a lek-mating bird of paradise, during 1981-1983 in Papua New Guinea. There was a high variance in mating success among males, with fewer than half of the individuals mating in any one year. This variance was independent of male-male interactions and disruptions. A role of female choice in sexual selection was suggested by the patterns of female visitation to courts and statistical correlations across males between phenotypic traits and mating success. Females repeatedly visited most males in their home ranges and began visiting males up to six weeks before mating. In one or more years, six aspects of male behavior and one morphological variable were positively correlated with mating success, but the probability values were not significant using a simultaneous inference test. Calculation of combined probability values across all three years revealed that one aspect of male display behavior, the probability of display, positively and significantly influenced mating status. The probability of display was also significantly correlated with relative mating success among males. Females showed strong fidelity to mates, both within and between seasons. Display sites of male Lawes' Parotia are variably dispersed, but mating success did not differ for grouped and solitary males. These data confirm an important role of female choice in sexual selection in birds of paradise but also suggest that female choice may be unrelated to the process of lek-initiation in this species. © 1990 The Society for the Study of Evolution.

  16. Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders.

    PubMed

    Jiménez-Moreno, Ester; Montalvillo-Jiménez, Laura; Santana, Andrés G; Gómez, Ana M; Jiménez-Osés, Gonzalo; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesús; Cañada, Francisco Javier; Gómez-Pinto, Irene; González, Carlos; Asensio, Juan Luis

    2016-05-25

    Development of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.

  17. Investigating yellow dung fly body size evolution in the field: Response to climate change?

    PubMed

    Blanckenhorn, Wolf U

    2015-08-01

    Uncovering genetic responses to selection in wild populations typically requires tracking individuals over generations and use of animal models. Our group monitored the body size of one Swiss Yellow Dung Fly (Scathophaga stercoraria; Diptera: Scathophagidae) field population over 15 years, including intermittent common-garden rearing in the laboratory to assess body size with minimized environmental and maximized genetic variation. Contrary to expectations based on repeated heritability and phenotypic selection assessments over the years (reported elsewhere), field body sizes declined by >10% and common-garden laboratory sizes by >5% from 1993 to 2009. Our results confirm the temperature-size rule (smaller when warmer) and, albeit entirely correlational, could be mediated by climate change, as over this period mean temperature at the site increased by 0.5°C, although alternative systematic environmental changes cannot be entirely excluded. Monitoring genetic responses to selection in wild invertebrate populations is thus possible, though indirect, and wild populations may evolve in directions not consistent with strongly positive directional selection favoring large body size. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  18. Two Decades of Negative Educational Selectivity of Mexican Migrants to the United States

    PubMed Central

    Rendall, Michael S.; Parker, Susan W.

    2015-01-01

    Immigration is commonly considered to be selective of more able individuals. Studies comparing the educational attainment of Mexican immigrants in the United States to that of the Mexican resident population support this characterization. Upward educational-attainment biases in both coverage and measurement, however, may be substantial in U.S. data sources. Moreover, differences in educational attainment by place size are very large within Mexico, and U.S. data sources provide no information on immigrants’ places of origin within Mexico. To address these problems, we use multiple sources of nationally-representative Mexican survey data to re-evaluate the educational selectivity of working-age Mexican migrants to the United States over the 1990s and 2000s. We document disproportionately rural and small-urban-area origins of Mexican migrants and a steep positive gradient of educational attainment by place size. We show that together these conditions induced strongly negative educational selection of Mexican migrants throughout the 1990s and 2000s. We interpret this finding as consistent with low returns to the education of unauthorized migrants and few opportunities for authorized migration. PMID:25995526

  19. The positive relationships between plant coverage, species richness, and aboveground biomass are ubiquitous across plant growth forms in semi-steppe rangelands.

    PubMed

    Sanaei, Anvar; Ali, Arshad; Chahouki, Mohammad Ali Zare

    2018-01-01

    The positive relationships between biodiversity and aboveground biomass are important for biodiversity conservation and greater ecosystem functioning and services that humans depend on. However, the interaction effects of plant coverage and biodiversity on aboveground biomass across plant growth forms (shrubs, forbs and grasses) in natural rangelands are poorly studied. Here, we hypothesized that, while accounting for environmental factors and disturbance intensities, the positive relationships between plant coverage, biodiversity, and aboveground biomass are ubiquitous across plant growth forms in natural rangelands. We applied structural equation models (SEMs) using data from 735 quadrats across 35 study sites in semi-steppe rangelands in Iran. The combination of plant coverage and species richness rather than Shannon's diversity or species diversity (a latent variable of species richness and evenness) substantially enhance aboveground biomass across plant growth forms. In all selected SEMs, plant coverage had a strong positive direct effect on aboveground biomass (β = 0.72 for shrubs, 0.84 for forbs and 0.80 for grasses), followed by a positive effect of species richness (β = 0.26 for shrubs, 0.05 for forbs and 0.09 for grasses), and topographic factors. Disturbance intensity had a negative effect on plant coverage, whereas it had a variable effect on species richness across plant growth forms. Plant coverage had a strong positive total effect on aboveground biomass (β = 0.84 for shrubs, 0.88 for forbs, and 0.85 for grasses), followed by a positive effect of species richness, and a negative effect of disturbance intensity across plant growth forms. Our results shed light on the management of rangelands that is high plant coverage can significantly improve species richness and aboveground biomass across plant growth forms. We also found that high disturbance intensity due to heavy grazing has a strong negative effect on plant coverage rather than species richness in semi-steppe rangelands. This study suggests that proper grazing systems (e.g. rotational system) based on carrying capacity and stocking rate of a rangeland may be helpful for biodiversity conservation, better grazing of livestock, improvement of plant coverage and enhancement of aboveground biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The genealogy of sequences containing multiple sites subject to strong selection in a subdivided population.

    PubMed Central

    Nordborg, Magnus; Innan, Hideki

    2003-01-01

    A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present. PMID:12663556

  1. The genealogy of sequences containing multiple sites subject to strong selection in a subdivided population.

    PubMed

    Nordborg, Magnus; Innan, Hideki

    2003-03-01

    A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present.

  2. Helix Fraying and Lipid-Dependent Structure of a Short Amphipathic Membrane-Bound Peptide Revealed by Solid-State NMR.

    PubMed

    Strandberg, Erik; Grau-Campistany, Ariadna; Wadhwani, Parvesh; Bürck, Jochen; Rabanal, Francesc; Ulrich, Anne S

    2018-06-14

    The amphipathic α-helical peptide KIA14 [(KIAGKIA) 2 -NH 2 ] was studied in membranes using circular dichroism and solid-state NMR spectroscopy to obtain global as well as local structural information. By analyzing 2 H NMR data from 10 analogues of KIA14 that were selectively labeled with Ala- d 3 , those positions that are properly folded into a helix could be determined within the membrane-bound peptide. The N-terminus was found to be unraveled, whereas positions 4-14 formed an ideal helix all the way to the C-terminus. The helicity did not change when Gly residues were replaced by Ala- d 3 but was reduced when Ile was replaced, indicating that large hydrophobic residues are required for membrane binding and helix formation. The reduced helicity was strongly correlated with a decrease in peptide-induced leakage from lipid vesicles. The orientation of the short KIA14 peptide was assessed in several lipid systems and compared with that of the longer KIA21 sequence [(KIAGKIA) 3 -NH 2 ]. In 1,2-dioleoyl- sn-glycero-3-phosphatidylcholine, both peptides are aligned flat on the membrane surface, whereas in 1,2-dimyristoyl- sn-glycero-3-phosphatidylcholine (DMPC)/1-myristoyl-2-hydroxy- sn-glycero-3-phosphatidylcholine (lyso-MPC) both are inserted into the membrane in an upright orientation. These two types of lipid systems had been selected for their strongly negative and positive spontaneous curvature, respectively. We propose that in these cases, the peptide orientation is largely determined by the lipid properties. On the other hand, in plain DMPC and 1,2-dilauroyl- sn-glycero-3-phosphatidylcholine, which have only a slight positive curvature, a marked difference in orientation is evident: the short KIA14 lies almost flat on the membrane surface, whereas the longer KIA21 is more tilted. We thus propose that out of the lipid systems tested here, DMPC (with hardly any curvature) is the least biased lipid system in which peptide orientation and realignment can be studied, allowing to compare and discriminate the intrinsic effects of the properties of the peptides as such.

  3. Maintenance of Genetic Variability under Strong Stabilizing Selection: A Two-Locus Model

    PubMed Central

    Gavrilets, S.; Hastings, A.

    1993-01-01

    We study a two locus model with additive contributions to the phenotype to explore the relationship between stabilizing selection and recombination. We show that if the double heterozygote has the optimum phenotype and the contributions of the loci to the trait are different, then any symmetric stabilizing selection fitness function can maintain genetic variability provided selection is sufficiently strong relative to linkage. We present results of a detailed analysis of the quadratic fitness function which show that selection need not be extremely strong relative to recombination for the polymorphic equilibria to be stable. At these polymorphic equilibria the mean value of the trait, in general, is not equal to the optimum phenotype, there exists a large level of negative linkage disequilibrium which ``hides'' additive genetic variance, and different equilibria can be stable simultaneously. We analyze dependence of different characteristics of these equilibria on the location of optimum phenotype, on the difference in allelic effect, and on the strength of selection relative to recombination. Our overall result that stabilizing selection does not necessarily eliminate genetic variability is compatible with some experimental results where the lines subject to strong stabilizing selection did not have significant reductions in genetic variability. PMID:8514145

  4. Predicting habits of vegetable parenting practices to facilitate the design of change programmes.

    PubMed

    Baranowski, Tom; Chen, Tzu-An; O'Connor, Teresia M; Hughes, Sheryl O; Diep, Cassandra S; Beltran, Alicia; Brand, Leah; Nicklas, Theresa; Baranowski, Janice

    2016-08-01

    Habit has been defined as the automatic performance of a usual behaviour. The present paper reports the relationships of variables from a Model of Goal Directed Behavior to four scales in regard to parents' habits when feeding their children: habit of (i) actively involving child in selection of vegetables; (ii) maintaining a positive vegetable environment; (iii) positive communications about vegetables; and (iv) controlling vegetable practices. We tested the hypothesis that the primary predictor of each habit variable would be the measure of the corresponding parenting practice. Internet survey data from a mostly female sample. Primary analyses employed regression modelling with backward deletion, controlling for demographics and parenting practices behaviour. Houston, Texas, USA. Parents of 307 pre-school (3-5-year-old) children. Three of the four models accounted for about 50 % of the variance in the parenting practices habit scales. Each habit scale was primarily predicted by the corresponding parenting practices scale (suggesting validity). The habit of active child involvement in vegetable selection was also most strongly predicted by two barriers and rudimentary self-efficacy; the habit of maintaining a positive vegetable environment by one barrier; the habit of maintaining positive communications about vegetables by an emotional scale; and the habit of controlling vegetable practices by a perceived behavioural control scale. The predictiveness of the psychosocial variables beyond parenting practices behaviour was modest. Discontinuing the habit of ineffective controlling parenting practices may require increasing the parent's perceived control of parenting practices, perhaps through simulated parent-child interactions.

  5. Rooted tRNAomes and evolution of the genetic code

    PubMed Central

    Pak, Daewoo; Du, Nan; Kim, Yunsoo; Sun, Yanni

    2018-01-01

    ABSTRACT We advocate for a tRNA- rather than an mRNA-centric model for evolution of the genetic code. The mechanism for evolution of cloverleaf tRNA provides a root sequence for radiation of tRNAs and suggests a simplified understanding of code evolution. To analyze code sectoring, rooted tRNAomes were compared for several archaeal and one bacterial species. Rooting of tRNAome trees reveals conserved structures, indicating how the code was shaped during evolution and suggesting a model for evolution of a LUCA tRNAome tree. We propose the polyglycine hypothesis that the initial product of the genetic code may have been short chain polyglycine to stabilize protocells. In order to describe how anticodons were allotted in evolution, the sectoring-degeneracy hypothesis is proposed. Based on sectoring, a simple stepwise model is developed, in which the code sectors from a 1→4→8→∼16 letter code. At initial stages of code evolution, we posit strong positive selection for wobble base ambiguity, supporting convergence to 4-codon sectors and ∼16 letters. In a later stage, ∼5–6 letters, including stops, were added through innovating at the anticodon wobble position. In archaea and bacteria, tRNA wobble adenine is negatively selected, shrinking the maximum size of the primordial genetic code to 48 anticodons. Because 64 codons are recognized in mRNA, tRNA-mRNA coevolution requires tRNA wobble position ambiguity leading to degeneracy of the code. PMID:29372672

  6. Radiography Faculty Engaged in Online Education: Perceptions of Effectiveness, Satisfaction, and Technological Self-efficacy.

    PubMed

    Cherry, Shirley J; Flora, Bethany H

    2017-01-01

    To assess radiography faculty perceptions of the effectiveness of online courses. An original survey instrument was created by selecting items from 3 instruments used in prior research and adding unique questions designed to elicit demographic data from faculty. The sample included a national dataset of radiography faculty members employed in Joint Review Committee on Education in Radiologic Technology-accredited programs in the United States. Findings showed that faculty perceptions of online course effectiveness are not affected significantly by faculty position, type of institution, faculty age, or years of teaching experience. Positive perceptions of the effectiveness of online courses moderately increased with years of teaching online courses, number of online courses taught in the past 5 years, and perceived competence with the use of technology. Faculty satisfaction with interaction in online courses moderately increased as the years of teaching online courses increased. However, the number of years of teaching online courses was not related to faculty satisfaction with teaching online courses or faculty satisfaction with institutional support. Online technology acceptance had a moderately positive relationship with perceived ease of use and a strong positive relationship with perceived usefulness of online technology. In addition, the use of technology-enhanced learning methods had a strong positive relationship with technological self-efficacy. Radiography faculty perceptions of the effectiveness of online courses improved with experience in teaching online courses and competence with use of technology. Perceived ease of use and perceived usefulness of online technology were related directly to online technology acceptance. Furthermore, faculty members with technological self-efficacy were more likely to use technology-enhanced learning methods in the online environment.

  7. Experimental evolution reveals high insecticide tolerance in Daphnia inhabiting farmland ponds

    PubMed Central

    Jansen, Mieke; Coors, Anja; Vanoverbeke, Joost; Schepens, Melissa; De Voogt, Pim; De Schamphelaere, Karel A C; De Meester, Luc

    2015-01-01

    Exposure of nontarget populations to agricultural chemicals is an important aspect of global change. We quantified the capacity of natural Daphnia magna populations to locally adapt to insecticide exposure through a selection experiment involving carbaryl exposure and a control. Carbaryl tolerance after selection under carbaryl exposure did not increase significantly compared to the tolerance of the original field populations. However, there was evolution of a decreased tolerance in the control experimental populations compared to the original field populations. The magnitude of this decrease was positively correlated with land use intensity in the neighbourhood of the ponds from which the original populations were sampled. The genetic change in carbaryl tolerance in the control rather than in the carbaryl treatment suggests widespread selection for insecticide tolerance in the field associated with land use intensity and suggests that this evolution comes at a cost. Our data suggest a strong impact of current agricultural land use on nontarget natural Daphnia populations. PMID:26029258

  8. Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel.

    PubMed

    Schmidt, Joshua M; Battlay, Paul; Gledhill-Smith, Rebecca S; Good, Robert T; Lumb, Chris; Fournier-Level, Alexandre; Robin, Charles

    2017-11-01

    Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster ; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies (GWAS) to identify DDT-associated polygenes and use selective sweep analyses to assess their adaptive significance. We identify and verify two candidate DDT resistance loci. A largely uncharacterized gene, CG10737 , has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1 , shows compelling evidence of positive selection. Copyright © 2017 by the Genetics Society of America.

  9. Photothermal Nanotherapeutics and Nanodiagnostics for Selective Killing of Bacteria Targeted with Gold Nanoparticles

    PubMed Central

    Zharov, Vladimir P.; Mercer, Kelly E.; Galitovskaya, Elena N.; Smeltzer, Mark S.

    2006-01-01

    We describe a new method for selective laser killing of bacteria targeted with light-absorbing gold nanoparticles conjugated with specific antibodies. The multifunctional photothermal (PT) microscope/spectrometer provides a real-time assessment of this new therapeutic intervention. In this integrated system, strong laser-induced overheating effects accompanied by the bubble-formation phenomena around clustered gold nanoparticles are the main cause of bacterial damage. PT imaging and time-resolved monitoring of the integrated PT responses assessed these effects. Specifically, we used this technology for selective killing of the Gram-positive bacterium Staphylococcus aureus by targeting the bacterial surface using 10-, 20-, and 40-nm gold particles conjugated with anti-protein A antibodies. Labeled bacteria were irradiated with focused laser pulses (420–570 nm, 12 ns, 0.1–5 J/cm2, 100 pulses), and laser-induced bacterial damage observed at different laser fluences and nanoparticle sizes was verified by optical transmission, electron microscopy, and conventional viability testing. PMID:16239330

  10. Two-Way Selection for Growth Rate in the Common Carp (CYPRINUS CARPIO L.)

    PubMed Central

    Moav, R.; Wohlfarth, G.

    1976-01-01

    The domesticated European carp was subjected to a two-way selection for growth rate. Five generations of mass selection for faster growth rate did not yield any response, but subsequent selection between groups (families) resulted in considerable progress while maintaining a large genetic variance. Selection for slow growth rate yielded relatively strong response for the first three generations. Random-bred control lines suffered from strong inbreeding depression and when two lines were crossed, the F1 showed a high degree of heterosis. Selection was performed on pond-raised fish, but growth rate was also tested in cages. A strong pond-cage genetic interaction was found. A theoretical explanation was suggested involving overdominance for fast growth rate and amplification through competition of intra-group but not inter-group variation. PMID:1248737

  11. Disruptive ecological selection on a mating cue.

    PubMed

    Merrill, Richard M; Wallbank, Richard W R; Bull, Vanessa; Salazar, Patricio C A; Mallet, James; Stevens, Martin; Jiggins, Chris D

    2012-12-22

    Adaptation to divergent ecological niches can result in speciation. Traits subject to disruptive selection that also contribute to non-random mating will facilitate speciation with gene flow. Such 'magic' or 'multiple-effect' traits may be widespread and important for generating biodiversity, but strong empirical evidence is still lacking. Although there is evidence that putative ecological traits are indeed involved in assortative mating, evidence that these same traits are under divergent selection is considerably weaker. Heliconius butterfly wing patterns are subject to positive frequency-dependent selection by predators, owing to aposematism and Müllerian mimicry, and divergent colour patterns are used by closely related species to recognize potential mates. The amenability of colour patterns to experimental manipulation, independent of other traits, presents an excellent opportunity to test their role during speciation. We conducted field experiments with artificial butterflies, designed to match natural butterflies with respect to avian vision. These were complemented with enclosure trials with live birds and real butterflies. Our experiments showed that hybrid colour-pattern phenotypes are attacked more frequently than parental forms. For the first time, we demonstrate disruptive ecological selection on a trait that also acts as a mating cue.

  12. Identification of squid species by melting temperature shifts on fluorescence melting curve analysis (FMCA) using single dual-labeled probe

    NASA Astrophysics Data System (ADS)

    Koh, Eunjung; Song, Ha Jeong; Kwon, Na Young; Kim, Gi Won; Lee, Kwang Ho; Jo, Soyeon; Park, Sujin; Park, Jihyun; Park, Eun Kyeong; Hwang, Seung Yong

    2017-06-01

    Real time PCR is a standard method for identification of species. One of limitations of the qPCR is that there would be false-positive result due to mismatched hybridization between target sequence and probe depending on the annealing temperature in the PCR condition. As an alternative, fluorescence melting curve analysis (FMCA) could be applied for species identification. FMCA is based on a dual-labeled probe. Even with subtle difference of target sequence, there are visible melting temperature (Tm) shift. One of FMCA applications is distinguishing organisms distributed and consumed globally as popular food ingredients. Their prices are set by species or country of origin. However, counterfeiting or distributing them without any verification procedure are becoming social problems and threatening food safety. Besides distinguishing them in naked eye is very difficult and almost impossible in any processed form. Therefore, it is necessary to identify species in molecular level. In this research three species of squids which have 1-2 base pair differences each are selected as samples since they have the same issue. We designed a probe which perfectly matches with one species and the others mismatches 2 and 1 base pair respectively and labeled with fluorophore and quencher. In an experiment with a single probe, we successfully distinguished them by Tm shift depending on the difference of base pair. By combining FMCA and qPCR chip, smaller-scale assay with higher sensitivity and resolution could be possible, andc furthermore, enabling results analysis with smart phone would realize point-of-care testing (POCT).

  13. Pervasive positive selection on duplicated and nonduplicated vertebrate protein coding genes.

    PubMed

    Studer, Romain A; Penel, Simon; Duret, Laurent; Robinson-Rechavi, Marc

    2008-09-01

    A stringent branch-site codon model was used to detect positive selection in vertebrate evolution. We show that the test is robust to the large evolutionary distances involved. Positive selection was detected in 77% of 884 genes studied. Most positive selection concerns a few sites on a single branch of the phylogenetic tree: Between 0.9% and 4.7% of sites are affected by positive selection depending on the branches. No functional category was overrepresented among genes under positive selection. Surprisingly, whole genome duplication had no effect on the prevalence of positive selection, whether the fish-specific genome duplication or the two rounds at the origin of vertebrates. Thus positive selection has not been limited to a few gene classes, or to specific evolutionary events such as duplication, but has been pervasive during vertebrate evolution.

  14. Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

    PubMed

    Oyebola, Kolapo M; Idowu, Emmanuel T; Olukosi, Yetunde A; Awolola, Taiwo S; Amambua-Ngwa, Alfred

    2017-06-29

    The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima's D) and integrated haplotype score (iHS) to identify genes under selection. Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima's D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known genomic signatures of selection from drug pressure and host immunity. This is evidence that P. falciparum populations explore common adaptive strategies that can be targeted for the development of new interventions.

  15. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study.

    PubMed

    van der Putten, Louis Jm; Visser, Nicole Cm; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc Plm; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon Fag; Pijnenborg, Johanna Ma

    2016-09-06

    Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.

  16. Anion-π Catalysis on Fullerenes.

    PubMed

    López-Andarias, Javier; Frontera, Antonio; Matile, Stefan

    2017-09-27

    Anion-π interactions on fullerenes are about as poorly explored as the use of fullerenes in catalysis. However, strong exchange-correlation contributions and the localized π holes on their surface promise unique selectivities. To elaborate on this promise, tertiary amines are attached nearby. Dependent on their positioning, the resulting stabilization of anionic transition states on fullerenes is shown to accelerate disfavored enolate addition and exo Diels-Alder reactions enantioselectively. The found selectivities are consistent with computational simulations, particularly concerning the discrimination of differently planarized and charge-delocalized enolate tautomers by anion-π interactions. Enolate-π interactions on fullerenes are much shorter than standard π-π interactions and anion-π interactions on planar surfaces, and alternative cation-π interactions are not observed. These findings open new perspectives with regard to anion-π interactions in general and the use of carbon allotropes in catalysis.

  17. Transition-Metal-Free Oxidative C(sp2 )-H Hydroxylation of Terpyridines: A HOMO-Raising Strategy for the Construction of a New Super-Stable Terpyridine Chromophores.

    PubMed

    Huang, Jiang-Bo; Bai, Xing-Feng; Li, Li; Zheng, Zhan-Jiang; Xu, Zheng; Cui, Yu-Ming; Cao, Jian; Xu, Li-Wen

    2017-03-23

    Direct functionalization of terpyridines is an increasingly important topic in the field of dyes and catalysis as well as supramolecular chemistry, but its synthesis and transformation is usually challenging. Herein, a HOMO-raising strategy is reported for the construction of a super-stable novel terpyridine chromophores, in which the selective oxidation of terpyridines at its 3-position was determined successfully to the synthesis of phenol-functionalization of terpyridines (TPyOHs) bearing a hydrogen bonding group. The corresponding TPyOHs displayed strong aggregation-induced emission and exhibited highly selective and visual detection of Zn II cation with a record green terpyridine-based luminophore with nanomolar sensitivity (125 nm). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. A Review of Selected Candidate Endophenotypes for Depression

    PubMed Central

    Goldstein, Brandon L.; Klein, Daniel N.

    2014-01-01

    Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. PMID:25006008

  19. Hot melt adhesive attachment pad

    NASA Technical Reports Server (NTRS)

    Fox, R. L.; Frizzill, A. W.; Little, B. D.; Progar, D. J.; Coultrip, R. H.; Couch, R. H.; Gleason, J. R.; Stein, B. A.; Buckley, J. D.; St.clair, T. L. (Inventor)

    1984-01-01

    A hot melt adhesive attachment pad for releasably securing distinct elements together is described which is particularly useful in the construction industry or a spatial vacuum environment. The attachment pad consists primarily of a cloth selectively impregnated with a charge of hot melt adhesive, a thermo-foil heater, and a thermo-cooler. These components are securely mounted in a mounting assembly. In operation, the operator activates the heating cycle transforming the hot melt adhesive to a substantially liquid state, positions the pad against the attachment surface, and activates the cooling cycle solidifying the adhesive and forming a strong, releasable bond.

  20. The genetic basis of adaptive pigmentation variation in Drosophila melanogaster.

    PubMed

    Pool, John E; Aquadro, Charles F

    2007-07-01

    In a broad survey of Drosophila melanogaster population samples, levels of abdominal pigmentation were found to be highly variable and geographically differentiated. A strong positive correlation was found between dark pigmentation and high altitude, suggesting adaptation to specific environments. DNA sequence polymorphism at the candidate gene ebony revealed a clear association with the pigmentation of homozygous third chromosome lines. The darkest lines sequenced had nearly identical haplotypes spanning 14.5 kb upstream of the protein-coding exons of ebony. Thus, natural selection may have elevated the frequency of an allele that confers dark abdominal pigmentation by influencing the regulation of ebony.

  1. On the universality of the two-point galaxy correlation function

    NASA Technical Reports Server (NTRS)

    Davis, Marc; Meiksin, Avery; Strauss, Michael A.; Da Costa, L. Nicolaci; Yahil, Amos

    1988-01-01

    The behavior of the two-point galaxy correlation function in volume-limited subsamples of three complete redshift surveys is investigated. The correlation length is shown to scale approximately as the square root of the distance limit in both the CfA and Southern Sky catalogs, but to be independent of the distance limit in the IRAS sample. This effect is found to be due to factors such as the large positive density fluctuations in the foreground of the optically selected catalogs biasing the correlation length estimate downward, and the brightest galaxies appearing to be more strongly clustered than the mean.

  2. Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome

    PubMed Central

    Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

    2016-01-01

    Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. PMID:27401230

  3. Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry

    PubMed Central

    2013-01-01

    Background Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima’s D, Fay and Wu’s H and Fu and Li’s D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Results Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. Conclusions We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation. PMID:23848512

  4. Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry.

    PubMed

    Hider, Jessica L; Gittelman, Rachel M; Shah, Tapan; Edwards, Melissa; Rosenbloom, Arnold; Akey, Joshua M; Parra, Esteban J

    2013-07-12

    Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation.

  5. Trans-species polymorphism at antimicrobial innate immunity cathelicidin genes of Atlantic cod and related species

    PubMed Central

    Árnason, Einar

    2015-01-01

    Natural selection, the most important force in evolution, comes in three forms. Negative purifying selection removes deleterious variation and maintains adaptations. Positive directional selection fixes beneficial variants, producing new adaptations. Balancing selection maintains variation in a population. Important mechanisms of balancing selection include heterozygote advantage, frequency-dependent advantage of rarity, and local and fluctuating episodic selection. A rare pathogen gains an advantage because host defenses are predominantly effective against prevalent types. Similarly, a rare immune variant gives its host an advantage because the prevalent pathogens cannot escape the host’s apostatic defense. Due to the stochastic nature of evolution, neutral variation may accumulate on genealogical branches, but trans-species polymorphisms are rare under neutrality and are strong evidence for balancing selection. Balanced polymorphism maintains diversity at the major histocompatibility complex (MHC) in vertebrates. The Atlantic cod is missing genes for both MHC-II and CD4, vital parts of the adaptive immune system. Nevertheless, cod are healthy in their ecological niche, maintaining large populations that support major commercial fisheries. Innate immunity is of interest from an evolutionary perspective, particularly in taxa lacking adaptive immunity. Here, we analyze extensive amino acid and nucleotide polymorphisms of the cathelicidin gene family in Atlantic cod and closely related taxa. There are three major clusters, Cath1, Cath2, and Cath3, that we consider to be paralogous genes. There is extensive nucleotide and amino acid allelic variation between and within clusters. The major feature of the results is that the variation clusters by alleles and not by species in phylogenetic trees and discriminant analysis of principal components. Variation within the three groups shows trans-species polymorphism that is older than speciation and that is suggestive of balancing selection maintaining the variation. Using Bayesian and likelihood methods positive and negative selection is evident at sites in the conserved part of the genes and, to a larger extent, in the active part which also shows episodic diversifying selection, further supporting the argument for balancing selection. PMID:26038731

  6. Masticophis flagellum selects florida scrub habitat at multiple spatial scales

    USGS Publications Warehouse

    Halstead, B.J.; Mushinsky, H.R.; McCoy, E.D.

    2009-01-01

    The use of space by individual animals strongly influences the spatial extent, abundance, and growth rates of their populations. We analyzed the spatial ecology and habitat selection of Masticophis flagellum (the coachwhip) at three different scales to determine which habitats are most important to this species. Home ranges and mean daily displacements of M. flagellum in Florida were large compared to individuals in other populations of this species. Home ranges contained a greater proportion of Florida scrub habitat than did the study site as a whole, and individuals selected Florida scrub habitat within their home ranges. For both selection of the home range within the study site and selection of habitats within the home range, mesic cutthroat and hydric swamp habitats were avoided. Standardized selection ratios of Florida scrub patches were positively correlated with lizard abundance. Several non-mutually exclusive mechanisms, including foraging success (prey abundance, prey vulnerability, and foraging efficiency), abundance of refugia, and thermoregulatory opportunity may underlie the selection of Florida scrub by M. flagellum. Historic rarity and anthropogenic loss and fragmentation of Florida scrub habitat, coupled with the long-distance movements, large home ranges, and selection of Florida scrub by M. flagellum, indicate that large contiguous tracts of land containing Florida scrub will be essential for the persistence of M. flagellum in central Florida. ?? 2009 by The Herpetologists' League, Inc.

  7. How we eat what we eat: identifying meal routines and practices most strongly associated with healthy and unhealthy dietary factors among young adults.

    PubMed

    Laska, Melissa N; Hearst, Mary O; Lust, Katherine; Lytle, Leslie A; Story, Mary

    2015-08-01

    (i) To examine associations between young adults' meal routines and practices (e.g. food preparation, meal skipping, eating on the run) and key dietary indicators (fruit/vegetable, fast-food and sugar-sweetened beverage intakes) and (ii) to develop indices of protective and risky meal practices most strongly associated with diet. Cross-sectional survey. Minneapolis/St. Paul metropolitan area, Minnesota (USA). A diverse sample of community college and public university students (n 1013). Meal routines and practices most strongly associated with healthy dietary patterns were related to home food preparation (i.e. preparing meals at home, preparing meals with vegetables) and meal regularity (i.e. routine consumption of evening meals and breakfast). In contrast, factors most strongly associated with poor dietary patterns included eating on the run, using media while eating and purchasing foods/beverages on campus. A Protective Factors Index, summing selected protective meal routines and practices, was positively associated with fruit/vegetable consumption and negatively associated with fast-food and sugar-sweetened beverage consumption (P<0·001). A Risky Factors Index yielded significant, positive associations with fast-food and sugar-sweetened beverage consumption (P<0·001). The probability test for the association between the Risky Factors Index and fruit/vegetable intake was P=0·05. Meal routines and practices were significantly associated with young adults' dietary patterns, suggesting that ways in which individuals structure mealtimes and contextual characteristics of eating likely influence food choice. Thus, in addition to considering specific food choices, it also may be important to consider the context of mealtimes in developing dietary messaging and guidelines.

  8. How we eat what we eat: Identifying meal routines and practices most strongly associated with healthy and unhealthy dietary factors among young adults

    PubMed Central

    Laska, Melissa N.; Hearst, Mary O.; Lust, Katherine; Lytle, Leslie; Story, Mary

    2017-01-01

    Objectives (a) To examine associations between young adult meal routines and practices (e.g., food preparation, meal skipping, eating on the run) and key dietary indicators (fruit/vegetable, fast food and sugar-sweetened beverage intake), and (b) to develop indices of protective and risky meal practices most strongly associated with diet. Design Cross-sectional survey. Setting Minneapolis/St. Paul metropolitan area, Minnesota (USA). Subjects A diverse sample of community college and public university (n=1,013) students. Results Meal routines and practices most strongly associated with healthy dietary patterns were related to home food preparation (i.e., preparing meals at home, preparing meals with vegetables) and meal regularity (i.e., routine consumption of evening meals and breakfast). In contrast, factors most strongly associated with poor dietary patterns included eating on the run, using media while eating, and purchasing foods/beverages on campus. A Protective Factors Index, summing selected protective meal routines and practices, was positively associated with fruit/vegetable consumption, and negatively associated with fast food and sugar-sweetened beverage consumption (p<0.001). A Risky Factors Index yielded significant, positive associations with fast food and sugar sweetened beverage (p<0.001) consumption. The probability test for the association between the Risky Factors Index and fruit/vegetable intake was p=0.05. Conclusions Meal routines and practices were significantly associated with young adult dietary patterns, suggesting that ways in which individuals structure mealtimes and contextual characteristics of eating likely influence food choice. Thus, in addition to considering specific food choices, it also may be important to consider the context of mealtimes in developing dietary messaging and guidelines. PMID:25439511

  9. Relationship between the Handball-Specific Complex-Test and Intermittent Field Test performance in professional players.

    PubMed

    Hermassi, Souhail; Hoffmeyer, Birgit; Irlenbusch, Lars; Fieseler, Georg; Noack, Frank; Delank, Karl-Stefan; Gabbett, Tim J; Souhaiel Chelly, Mohamed; Schwesig, René

    2018-01-01

    We investigated the relationship between the Handball Complex-Test (HBCT) and two selected field performance tests (the repeated sprint ability [RSA], and the Yo-Yo Intermittent Recovery Test) in elite handball players. Nineteen handball players (age: 25.7±5.1 years) were drawn from the First Professional German League. The HBCT consists of four activity series (AS): agility parcours, defensive action, sprint (10 m, 20 m) and throw-on-goal parcours; these activities were completed twice, with five active pauses of 30-35 s, and a follow-up of recovery over the subsequent 10 minutes. The RSA comprised 6 x (15+15 m) sprints starting every 20 s; scoring noted best time (RSAbest), total time (RSATT) and decrement (RSAdec). In the Yo-Yo Intermittent Recover, we recorded the total distance covered (TD). Heart rates (HR) were recorded throughout and recovery was assessed for measurements immediately post-test (R0) and 10 minutes after completing the test (R10). A strong correlation was found between HBCT and fastest 10 m and 20 m RSA sprint times (r=0.811, r=0.815, respectively). Also, the HBCT total 10 m and 20 m sprint times showed a strong positive association with RSATT (r=0.70; r=0.63, respectively), and the RSA heart rate post-test was strongly correlated with the HBCT heart rate after round two (r=0.865). Data from the match-specific HBCT Test shows a strong positive association with other more generic intermittent field test measurements. These observations support the validity of using the generic tests to monitor current fitness and responses to training in team handball players.

  10. [Preparation of freeze - drying control materials of IgG antibody against Schistosoma japonicum for immunodetection kits].

    PubMed

    Jin, Huang; Chun-Lian, Tang; Zu-Wu, Tu; Li, Tang; Ke-Hui, Zhang; Qian, Li; Jun, Ye

    2018-04-18

    To prepare freeze-drying control materials of IgG antibody against Schistosoma japonicum for detection kits. The serum samples of schistosomiasis patients from endemic areas and normal people without history of schistosome infection or contact with infested water in Hubei Province were collected. All the sera were detected by the method approved by China Food and Drug Administration and selected for preparation of quality control samples. Totally twelve positive quality control materials, ten negative quality control materials, and one sensitive and one precision quality control materials were screened. According to the positive serum level, the positive degrees of quality control materials were divided into strong, medium and weak levels. The stability could be valid for one year. The freeze-drying quality control materials of IgG antibody against S. japonicum for detection kits are prepared. They are easy to use and have good stability, and therefore, they may meet the requirement of quality control for the detection of schistosomiasis diagnostics kits.

  11. Dissecting relative contributions of cis- and trans-determinants to nucleosome distribution by comparing Tetrahymena macronuclear and micronuclear chromatin.

    PubMed

    Xiong, Jie; Gao, Shan; Dui, Wen; Yang, Wentao; Chen, Xiao; Taverna, Sean D; Pearlman, Ronald E; Ashlock, Wendy; Miao, Wei; Liu, Yifan

    2016-12-01

    The ciliate protozoan Tetrahymena thermophila contains two types of structurally and functionally differentiated nuclei: the transcriptionally active somatic macronucleus (MAC) and the transcriptionally silent germ-line micronucleus (MIC). Here, we demonstrate that MAC features well-positioned nucleosomes downstream of transcription start sites and flanking splice sites. Transcription-associated trans-determinants promote nucleosome positioning in MAC. By contrast, nucleosomes in MIC are dramatically delocalized. Nucleosome occupancy in MAC and MIC are nonetheless highly correlated with each other, as well as with in vitro reconstitution and predictions based upon DNA sequence features, revealing unexpectedly strong contributions from cis-determinants. In particular, well-positioned nucleosomes are often matched with GC content oscillations. As many nucleosomes are coordinately accommodated by both cis- and trans-determinants, we propose that their distribution is shaped by the impact of these nucleosomes on the mutational and transcriptional landscape, and driven by evolutionary selection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Bateman's principle is reversed in a cooperatively breeding bird.

    PubMed

    Apakupakul, Kathleen; Rubenstein, Dustin R

    2015-04-01

    Bateman's principle is not only used to explain sex differences in mating behaviour, but also to determine which sex has the greater opportunity for sexual selection. It predicts that the relationship between the number of mates and the number of offspring produced should be stronger for males than for females. Yet, it is unclear whether Bateman's principle holds in cooperatively breeding systems where the strength of selection on traits used in intrasexual competition is high in both sexes. We tested Bateman's principle in the cooperatively breeding superb starling (Lamprotornis superbus), finding that only females showed a significant, positive Bateman gradient. We also found that the opportunity for selection was on average higher in females, but that its strength and direction oscillated through time. These data are consistent with the hypothesis that sexual selection underlies the female trait elaboration observed in superb starlings and other cooperative breeders. Even though the Bateman gradient was steeper for females than for males, the year-to-year oscillation in the strength and direction of the opportunity for selection likely explains why cooperative breeders do not exhibit sexual role reversal. Thus, Bateman's principle may not hold in cooperative breeders where both sexes appear to be under mutually strong sexual selection. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  13. Changes in Malaria Parasite Drug Resistance in an Endemic Population Over a 25-Year Period With Resulting Genomic Evidence of Selection

    PubMed Central

    Nwakanma, Davis C.; Duffy, Craig W.; Amambua-Ngwa, Alfred; Oriero, Eniyou C.; Bojang, Kalifa A.; Pinder, Margaret; Drakeley, Chris J.; Sutherland, Colin J.; Milligan, Paul J.; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Clark, Taane G.; Greenwood, Brian M.; Conway, David J.

    2014-01-01

    Background. Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. Methods. We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived parasite-positive blood samples of a Gambian population between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin combination therapy. We separately performed genome-wide sequence analysis of 52 clinical isolates from 2008 to prospect for loci under recent directional selection. Results. Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and mdr1 genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulfadoxine resistance. Temporal changes fit a model incorporating likely selection coefficients over the period. Three of the drug resistance loci were in the top 4 regions under strong selection implicated by the genome-wide analysis. Conclusions. Genome-wide polymorphism analysis of an endemic population sample robustly identifies loci with detailed documentation of recent selection, demonstrating power to prospectively detect emerging drug resistance genes. PMID:24265439

  14. Optical filter selection for high confidence discrimination of strongly overlapping infrared chemical spectra.

    PubMed

    Major, Kevin J; Poutous, Menelaos K; Ewing, Kenneth J; Dunnill, Kevin F; Sanghera, Jasbinder S; Aggarwal, Ishwar D

    2015-09-01

    Optical filter-based chemical sensing techniques provide a new avenue to develop low-cost infrared sensors. These methods utilize multiple infrared optical filters to selectively measure different response functions for various chemicals, dependent on each chemical's infrared absorption. Rather than identifying distinct spectral features, which can then be used to determine the identity of a target chemical, optical filter-based approaches rely on measuring differences in the ensemble response between a given filter set and specific chemicals of interest. Therefore, the results of such methods are highly dependent on the original optical filter choice, which will dictate the selectivity, sensitivity, and stability of any filter-based sensing method. Recently, a method has been developed that utilizes unique detection vector operations defined by optical multifilter responses, to discriminate between volatile chemical vapors. This method, comparative-discrimination spectral detection (CDSD), is a technique which employs broadband optical filters to selectively discriminate between chemicals with highly overlapping infrared absorption spectra. CDSD has been shown to correctly distinguish between similar chemicals in the carbon-hydrogen stretch region of the infrared absorption spectra from 2800-3100 cm(-1). A key challenge to this approach is how to determine which optical filter sets should be utilized to achieve the greatest discrimination between target chemicals. Previous studies used empirical approaches to select the optical filter set; however this is insufficient to determine the optimum selectivity between strongly overlapping chemical spectra. Here we present a numerical approach to systematically study the effects of filter positioning and bandwidth on a number of three-chemical systems. We describe how both the filter properties, as well as the chemicals in each set, affect the CDSD results and subsequent discrimination. These results demonstrate the importance of choosing the proper filter set and chemicals for comparative discrimination, in order to identify the target chemical of interest in the presence of closely matched chemical interferents. These findings are an integral step in the development of experimental prototype sensors, which will utilize CDSD.

  15. China's Land Market Auctions: Evidence of Corruption?

    PubMed

    Cai, Hongbin; Henderson, J Vernon; Zhang, Qinghua

    2013-01-01

    This paper studies the urban land market in China in 2003-2007. In China, all urban land is owned by the state. Leasehold use rights for land for (re)development are sold by city governments and are a key source of city revenue. Leasehold sales are viewed as a major venue for corruption, prompting a number of reforms over the years. Reforms now require all leasehold rights be sold at public auction. There are two main types of auction: regular English auction and an unusual type which we call a "two stage auction". The latter type of auction seems more subject to corruption, and to side deals between potential bidders and the auctioneer. Absent corruption, theory suggests that two stage auctions would most likely maximize sales revenue for properties which are likely to have relatively few bidders, or are "cold", which would suggest negative selection on property unobservables into such auctions. However, if such auctions are more corruptible, that could involve positive selection as city officials divert hotter properties to a more corruptible auction form. The paper finds that, overall, sales prices are lower for two stage auctions, and there is strong evidence of positive selection. The price difference is explained primarily by the fact that two stage auctions typically have just one bidder, or no competition despite the vibrant land market in Chinese cities.

  16. China’s Land Market Auctions: Evidence of Corruption?

    PubMed Central

    Cai, Hongbin; Henderson, J. Vernon; Zhang, Qinghua

    2013-01-01

    This paper studies the urban land market in China in 2003—2007. In China, all urban land is owned by the state. Leasehold use rights for land for (re)development are sold by city governments and are a key source of city revenue. Leasehold sales are viewed as a major venue for corruption, prompting a number of reforms over the years. Reforms now require all leasehold rights be sold at public auction. There are two main types of auction: regular English auction and an unusual type which we call a “two stage auction”. The latter type of auction seems more subject to corruption, and to side deals between potential bidders and the auctioneer. Absent corruption, theory suggests that two stage auctions would most likely maximize sales revenue for properties which are likely to have relatively few bidders, or are “cold”, which would suggest negative selection on property unobservables into such auctions. However, if such auctions are more corruptible, that could involve positive selection as city officials divert hotter properties to a more corruptible auction form. The paper finds that, overall, sales prices are lower for two stage auctions, and there is strong evidence of positive selection. The price difference is explained primarily by the fact that two stage auctions typically have just one bidder, or no competition despite the vibrant land market in Chinese cities. PMID:25506125

  17. Mechanistic Peptidomics: Factors That Dictate Specificity in the Formation of Endogenous Peptides in Human Milk*

    PubMed Central

    Guerrero, Andres; Dallas, David C.; Contreras, Stephanie; Chee, Sabrina; Parker, Evan A.; Sun, Xin; Dimapasoc, Lauren; Barile, Daniela; German, J. Bruce; Lebrilla, Carlito B.

    2014-01-01

    An extensive mass spectrometry analysis of the human milk peptidome has revealed almost 700 endogenous peptides from 30 different proteins. Two in-house computational tools were created and used to visualize and interpret the data through both alignment of the peptide quasi-molecular ion intensities and estimation of the differential enzyme participation. These results reveal that the endogenous proteolytic activity in the mammary gland is remarkably specific and well conserved. Certain proteins—not necessarily the most abundant ones—are digested by the proteases present in milk, yielding endogenous peptides from selected regions. Our results strongly suggest that factors such as the presence of specific proteases, the position and concentration of cleavage sites, and, more important, the intrinsic disorder of segments of the protein drive this proteolytic specificity in the mammary gland. As a consequence of this selective hydrolysis, proteins that typically need to be cleaved at specific positions in order to exert their activity are properly digested, and bioactive peptides encoded in certain protein sequences are released. Proteins that must remain intact in order to maintain their activity in the mammary gland or in the neonatal gastrointestinal tract are unaffected by the hydrolytic environment present in milk. These results provide insight into the intrinsic structural mechanisms that facilitate the selectivity of the endogenous milk protease activity and might be useful to those studying the peptidomes of other biofluids. PMID:25172956

  18. Effects of cytosine methylation on transcription factor binding sites

    PubMed Central

    2014-01-01

    Background DNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important. Results We found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines “traffic lights”. We observed a strong selection against CpG “traffic lights” within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions. Conclusions Our results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription. PMID:24669864

  19. Detecting Selection on Protein Stability through Statistical Mechanical Models of Folding and Evolution

    PubMed Central

    Bastolla, Ugo

    2014-01-01

    The properties of biomolecules depend both on physics and on the evolutionary process that formed them. These two points of view produce a powerful synergism. Physics sets the stage and the constraints that molecular evolution has to obey, and evolutionary theory helps in rationalizing the physical properties of biomolecules, including protein folding thermodynamics. To complete the parallelism, protein thermodynamics is founded on the statistical mechanics in the space of protein structures, and molecular evolution can be viewed as statistical mechanics in the space of protein sequences. In this review, we will integrate both points of view, applying them to detecting selection on the stability of the folded state of proteins. We will start discussing positive design, which strengthens the stability of the folded against the unfolded state of proteins. Positive design justifies why statistical potentials for protein folding can be obtained from the frequencies of structural motifs. Stability against unfolding is easier to achieve for longer proteins. On the contrary, negative design, which consists in destabilizing frequently formed misfolded conformations, is more difficult to achieve for longer proteins. The folding rate can be enhanced by strengthening short-range native interactions, but this requirement contrasts with negative design, and evolution has to trade-off between them. Finally, selection can accelerate functional movements by favoring low frequency normal modes of the dynamics of the native state that strongly correlate with the functional conformation change. PMID:24970217

  20. Variable Mesophyll Conductance among Soybean Cultivars Sets a Tradeoff between Photosynthesis and Water-Use-Efficiency1[OPEN

    PubMed Central

    2017-01-01

    Photosynthetic efficiency is a critical determinant of crop yield potential, although it remains below the theoretical optimum in modern crop varieties. Enhancing mesophyll conductance (i.e. the rate of carbon dioxide diffusion from substomatal cavities to the sites of carboxylation) may increase photosynthetic and water use efficiencies. To improve water use efficiency, mesophyll conductance should be increased without concomitantly increasing stomatal conductance. Here, we partition the variance in mesophyll conductance to within- and among-cultivar components across soybean (Glycine max) grown under both controlled and field conditions and examine the covariation of mesophyll conductance with photosynthetic rate, stomatal conductance, water use efficiency, and leaf mass per area. We demonstrate that mesophyll conductance varies more than 2-fold and that 38% of this variation is due to cultivar identity. As expected, mesophyll conductance is positively correlated with photosynthetic rates. However, a strong positive correlation between mesophyll and stomatal conductance among cultivars apparently impedes positive scaling between mesophyll conductance and water use efficiency in soybean. Contrary to expectations, photosynthetic rates and mesophyll conductance both increased with increasing leaf mass per area. The presence of genetic variation for mesophyll conductance suggests that there is potential to increase photosynthesis and mesophyll conductance by selecting for greater leaf mass per area. Increasing water use efficiency, though, is unlikely unless there is simultaneous stabilizing selection on stomatal conductance. PMID:28270627

  1. Development of 5-Substituted N-Methylmorphinan-6-ones as Potent Opioid Analgesics with Improved Side-Effect Profile.

    PubMed

    Schmidhammer, Helmut; Spetea, Mariana

    2012-01-01

    One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N-methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and efficacy at opioid receptors. This paper describes a representative strategy to improve the therapeutic usefulness of opioid analgesics from the morphinan class of drugs by targeting position 5. The focus is on chemical and biological studies and structure-activity relationships of this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl and benzyl group at position 5 as strong opioid antinociceptive agents with reduced propensity to cause undesired effects compared to morphine although interacting selectively with MORs.

  2. Planning for success: desired characteristics of special operations surgeons, a pilot study.

    PubMed

    Campbell, Barrett H; Alderman, Shawn M

    2012-01-01

    Selection criteria for Special Operations Forces (SOF) physicians are often unclear to potential candidates without prior SOF experience. To date, no published career resource exists to guide the careers of physicians interested in becoming a SOF surgeon. Using a survey tool, desirable characteristics and personal attributes were identified that can be used to inform candidate career decisions and better prepare them for a future position in Special Operations. A descriptive, cross-sectional survey instrument was developed and distributed to current Army SOF Command Surgeons for further distribution to subordinate surgeons. RESULTS were analyzed as a cohort and by subordinate command. Respondents consisted of current SOF Surgeons. Uniformly, the individual characteristics most strongly desired are professionalism, being a team player, and leadership. Possessing or obtaining Airborne and Flight Surgeon qualifications prior to consideration for a surgeon position was highly desired. Residency training within Family Medicine or Emergency Medicine constituted the vast majority of specialty preference. Understanding which characteristics and attributes are desirable to current surgeons and commanders can aid physicians interested in SOF surgeon positions. Using this study and future studies can guide career planning and foster the selection of ideally trained physicians who will operate at the tip of the spear. The views expressed are those of the author(s) and do not reflect the official policy of the Department of the Army, the Department of Defense or the U.S. Government. 2012.

  3. Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies

    PubMed Central

    Jiang, Ke; Zhang, Peng

    2011-01-01

    TRPA1 is a calcium ion channel protein recently identified as the infrared receptor in pit organ-containing snakes. Therefore, understanding the molecular evolution of TRPA1 may help to illuminate the origin of “heat vision” in snakes and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this end, we sequenced the infrared sensory gene TRPA1 in 24 snake species, representing nine snake families and multiple non-snake outgroups. We found that TRPA1 is under strong positive selection in the pit-bearing snakes studied, but not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a gene closely related to TRPA1, was found to be under strong purifying selection in all the species studied, with no difference in the strength of selection between pit-bearing snakes and non-pit snakes. This finding demonstrates that the adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes and may be related to the functional modification for detecting infrared radiation. In addition, by comparing the TRPA1 protein sequences, we identified 11 amino acid sites that were diverged in pit-bearing snakes but conserved in non-pit snakes and other vertebrates, 21 sites that were diverged only within pit-vipers but conserved in the remaining snakes. These specific amino acid substitutions may be potentially functional important for infrared sensing. PMID:22163322

  4. Genetic variation and correlated changes in reproductive performance of a red tilapia line selected for improved growth over three generations.

    PubMed

    Thoa, Ngo Phu; Hamzah, Azhar; Nguyen, Nguyen Hong

    2017-09-01

    The present study examines genetic variation and correlated changes in reproductive performance traits in a red tilapia (Oreochromis spp.) population selected over three generations for improved growth. A total of 328 breeding females (offspring of 111 sires and 118 dams) had measurements of body weight prior to spawning (WBS), number of fry at hatching (NFH), total fry weight (TFW) and number of dead fry (NDF) or mortality of fry including unhatched eggs at hatching (MFH). Restricted maximum likelihood (REML) analysis in a multi-trait model showed that there are heritable genetic components for all traits studied. The heritability for WBS was very high (0.80). The estimates for traits related to fecundity (NFH, TFW) and survival (NDF) were low and they were associated with high standard errors. Genetic correlations of WBS with other reproductive performance traits (NFH, TFW and NDF) were generally positive. However, NFH was negatively correlated genetically with TFW. As expected, body measurements during growth stage exhibited strong positive genetic correlations with WBS. The genetic correlations between body traits and reproductive performance (NFH, TFW, NDF) were not significant. Correlated responses in reproductive traits were measured as changes in least squares means between generations or spawning years. Except for WBS that increased with the selection programs, the phenotypic changes in other reproductive traits observed were not statistically significant (P>0.05). It is concluded that the selection program for red tilapia has resulted in very little changes in reproductive performance of the animals after three generations. However, periodic monitoring of genetic changes in fecundity and fitness related traits such as NDF or MFH should be made in selective breeding programs for red tilapia. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

    PubMed Central

    Hsieh, PingHsun; Veeramah, Krishna R.; Lachance, Joseph; Tishkoff, Sarah A.; Wall, Jeffrey D.; Hammer, Michael F.; Gutenkunst, Ryan N.

    2016-01-01

    African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors. PMID:26888263

  6. Simultaneous improvement of grain yield and protein content in durum wheat by different phenotypic indices and genomic selection.

    PubMed

    Rapp, M; Lein, V; Lacoudre, F; Lafferty, J; Müller, E; Vida, G; Bozhanova, V; Ibraliu, A; Thorwarth, P; Piepho, H P; Leiser, W L; Würschum, T; Longin, C F H

    2018-06-01

    Simultaneous improvement of protein content and grain yield by index selection is possible but its efficiency largely depends on the weighting of the single traits. The genetic architecture of these indices is similar to that of the primary traits. Grain yield and protein content are of major importance in durum wheat breeding, but their negative correlation has hampered their simultaneous improvement. To account for this in wheat breeding, the grain protein deviation (GPD) and the protein yield were proposed as targets for selection. The aim of this work was to investigate the potential of different indices to simultaneously improve grain yield and protein content in durum wheat and to evaluate their genetic architecture towards genomics-assisted breeding. To this end, we investigated two different durum wheat panels comprising 159 and 189 genotypes, which were tested in multiple field locations across Europe and genotyped by a genotyping-by-sequencing approach. The phenotypic analyses revealed significant genetic variances for all traits and heritabilities of the phenotypic indices that were in a similar range as those of grain yield and protein content. The GPD showed a high and positive correlation with protein content, whereas protein yield was highly and positively correlated with grain yield. Thus, selecting for a high GPD would mainly increase the protein content whereas a selection based on protein yield would mainly improve grain yield, but a combination of both indices allows to balance this selection. The genome-wide association mapping revealed a complex genetic architecture for all traits with most QTL having small effects and being detected only in one germplasm set, thus limiting the potential of marker-assisted selection for trait improvement. By contrast, genome-wide prediction appeared promising but its performance strongly depends on the relatedness between training and prediction sets.

  7. Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations.

    PubMed

    Sun, Zhizeng; Mehta, Shrenik C; Adamski, Carolyn J; Gibbs, Richard A; Palzkill, Timothy

    2016-09-12

    CphA is a Zn(2+)-dependent metallo-β-lactamase that efficiently hydrolyzes only carbapenem antibiotics. To understand the sequence requirements for CphA function, single codon random mutant libraries were constructed for residues in and near the active site and mutants were selected for E. coli growth on increasing concentrations of imipenem, a carbapenem antibiotic. At high concentrations of imipenem that select for phenotypically wild-type mutants, the active-site residues exhibit stringent sequence requirements in that nearly all residues in positions that contact zinc, the substrate, or the catalytic water do not tolerate amino acid substitutions. In addition, at high imipenem concentrations a number of residues that do not directly contact zinc or substrate are also essential and do not tolerate substitutions. Biochemical analysis confirmed that amino acid substitutions at essential positions decreased the stability or catalytic activity of the CphA enzyme. Therefore, the CphA active - site is fragile to substitutions, suggesting active-site residues are optimized for imipenem hydrolysis. These results also suggest that resistance to inhibitors targeted to the CphA active site would be slow to develop because of the strong sequence constraints on function.

  8. Ionospheric disturbances under low solar activity conditions

    NASA Astrophysics Data System (ADS)

    Buresova, D.; Lastovicka, J.; Hejda, P.; Bochnicek, J.

    2014-07-01

    The paper is focused on ionospheric response to occasional magnetic disturbances above selected ionospheric stations located at middle latitudes of the Northern and Southern Hemisphere under extremely low solar activity conditions of 2007-2009. We analyzed changes in the F2 layer critical frequency foF2 and the F2 layer peak height hmF2 against 27-days running mean obtained for different longitudinal sectors of both hemispheres for the initial, main and recovery phases of selected magnetic disturbances. Our analysis showed that the effects on the middle latitude ionosphere of weak-to-moderate CIR-related magnetic storms, which mostly occur around solar minimum period, could be comparable with the effects of strong magnetic storms. In general, both positive and negative deviations of foF2 and hmF2 have been observed independent on season and location. However positive effects on foF2 prevailed and were more significant. Observations of stormy ionosphere also showed large departures from the climatology within storm recovery phase, which are comparable with those usually observed during the storm main phase. The IRI STORM model gave no reliable corrections of foF2 for analyzed events.

  9. Influence of metal substrates on the detection of explosive residues with laser-induced breakdown spectroscopy.

    PubMed

    Gottfried, Jennifer L

    2013-02-01

    Laser-induced breakdown spectroscopy is a promising approach for explosive residue detection, but several limitations to its widespread use remain. One issue is that the emission spectra of the residues are dependent on the substrate composition because some of the substrate is usually entrained in the laser-induced plasma and the laser-material interaction can be significantly affected by the substrate type. Here, we have demonstrated that despite the strong spectral variation in cyclotrimethylenetrinitramine (RDX) residues applied to various metal substrates, classification of the RDX residue independent of substrate type is feasible. Several approaches to improving the chemometric models based on partial least squares discriminant analysis (PLS-DA) have been described: classifying the RDX residue spectra together in one class independent of substrate, using selected emission intensities and ratios to increase the true positive rate (TPR) and decrease the false positive rate (FPR), and fusing the results from two PLS-DA models generated using the full broadband spectra and selected intensities and ratios. The combination of these approaches resulted in a TPR of 97.5% and a FPR of 1.0% for RDX classification on metal substrates.

  10. Invasion of Ancestral Mammals into Dim-light Environments Inferred from Adaptive Evolution of the Phototransduction Genes.

    PubMed

    Wu, Yonghua; Wang, Haifeng; Hadly, Elizabeth A

    2017-04-20

    Nocturnality is a key evolutionary innovation of mammals that enables mammals to occupy relatively empty nocturnal niches. Invasion of ancestral mammals into nocturnality has long been inferred from the phylogenetic relationships of crown Mammalia, which is primarily nocturnal, and crown Reptilia, which is primarily diurnal, although molecular evidence for this is lacking. Here we used phylogenetic analyses of the vision genes involved in the phototransduction pathway to predict the diel activity patterns of ancestral mammals and reptiles. Our results demonstrated that the common ancestor of the extant Mammalia was dominated by positive selection for dim-light vision, supporting the predominate nocturnality of the ancestral mammals. Further analyses showed that the nocturnality of the ancestral mammals was probably derived from the predominate diurnality of the ancestral amniotes, which featured strong positive selection for bright-light vision. Like the ancestral amniotes, the common ancestor of the extant reptiles and various taxa in Squamata, one of the main competitors of the temporal niches of the ancestral mammals, were found to be predominate diurnality as well. Despite this relatively apparent temporal niche partitioning between ancestral mammals and the relevant reptiles, our results suggested partial overlap of their temporal niches during crepuscular periods.

  11. Coinfection and vertical transmission of Brucella and Morbillivirus in a neonatal sperm whale (Physeter macrocephalus) in Hawaii, USA.

    PubMed

    West, Kristi L; Levine, Gregg; Jacob, Jessica; Jensen, Brenda; Sanchez, Susan; Colegrove, Kathleen; Rotstein, David

    2015-01-01

    The viral genus Morbillivirus and the bacterial genus Brucella have emerged as important groups of pathogens that are known to affect cetacean health on a global scale, but neither pathogen has previously been reported from endangered sperm whales (Physeter macrocephalus). A female neonate sperm whale stranded alive and died near Laie on the island of Oahu, Hawaii, US, in May of 2011. Congestion of the cerebrum and enlarged lymph nodes were noted on the gross necropsy. Microscopic findings included lymphoid depletion, chronic meningitis, and pneumonia, suggesting an in utero infection. Cerebrum, lung, umbilicus, and select lymph nodes (tracheobronchial and mediastinal) were positive for Brucella by PCR. Brucella sp. was also cultured from the cerebrum and from mediastinal and tracheobronchial lymph nodes. Twelve different tissues were screened for Morbillivirus by reverse-transcriptase (RT)-PCR and select tissues by immunohistochemistry, but only the tracheobronchial lymph node and spleen were positive by RT-PCR. Pathologic findings observed were likely a result of Brucella, but Morbillivirus may have played a key role in immune suppression of the mother and calf. The in utero infection in this individual strongly supports vertical transmission of both pathogens.

  12. Condition-dependent reproductive effort in frogs infected by a widespread pathogen

    PubMed Central

    Roznik, Elizabeth A.; Sapsford, Sarah J.; Pike, David A.; Schwarzkopf, Lin; Alford, Ross A.

    2015-01-01

    To minimize the negative effects of an infection on fitness, hosts can respond adaptively by altering their reproductive effort or by adjusting their timing of reproduction. We studied effects of the pathogenic fungus Batrachochytrium dendrobatidis on the probability of calling in a stream-breeding rainforest frog (Litoria rheocola). In uninfected frogs, calling probability was relatively constant across seasons and body conditions, but in infected frogs, calling probability differed among seasons (lowest in winter, highest in summer) and was strongly and positively related to body condition. Infected frogs in poor condition were up to 40% less likely to call than uninfected frogs, whereas infected frogs in good condition were up to 30% more likely to call than uninfected frogs. Our results suggest that frogs employed a pre-existing, plastic, life-history strategy in response to infection, which may have complex evolutionary implications. If infected males in good condition reproduce at rates equal to or greater than those of uninfected males, selection on factors affecting disease susceptibility may be minimal. However, because reproductive effort in infected males is positively related to body condition, there may be selection on mechanisms that limit the negative effects of infections on hosts. PMID:26063847

  13. How Changes in Anti-SD Sequences Would Affect SD Sequences in Escherichia coli and Bacillus subtilis.

    PubMed

    Abolbaghaei, Akram; Silke, Jordan R; Xia, Xuhua

    2017-05-05

    The 3' end of the small ribosomal RNAs (ssu rRNA) in bacteria is directly involved in the selection and binding of mRNA transcripts during translation initiation via well-documented interactions between a Shine-Dalgarno (SD) sequence located upstream of the initiation codon and an anti-SD (aSD) sequence at the 3' end of the ssu rRNA. Consequently, the 3' end of ssu rRNA (3'TAIL) is strongly conserved among bacterial species because a change in the region may impact the translation of many protein-coding genes. Escherichia coli and Bacillus subtilis differ in their 3' ends of ssu rRNA, being GAUC ACCUCCUUA 3' in E. coli and GAUC ACCUCCUU UCU3' or GAUC ACCUCCUU UCUA3' in B. subtilis Such differences in 3'TAIL lead to species-specific SDs (designated SD Ec for E. coli and SD Bs for B. subtilis ) that can form strong and well-positioned SD/aSD pairing in one species but not in the other. Selection mediated by the species-specific 3'TAIL is expected to favor SD Bs against SD Ec in B. subtilis , but favor SD Ec against SD Bs in E. coli Among well-positioned SDs, SD Ec is used more in E. coli than in B. subtilis , and SD Bs more in B. subtilis than in E. coli Highly expressed genes and genes of high translation efficiency tend to have longer SDs than lowly expressed genes and genes with low translation efficiency in both species, but more so in B. subtilis than in E. coli Both species overuse SDs matching the bolded part of the 3'TAIL shown above. The 3'TAIL difference contributes to the host specificity of phages. Copyright © 2017 Abolbaghaei et al.

  14. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation: Efficacy of alectinib against ALK G1269A mutated cells.

    PubMed

    Yoshimura, Yasushi; Kurasawa, Mitsue; Yorozu, Keigo; Puig, Oscar; Bordogna, Walter; Harada, Naoki

    2016-03-01

    Alectinib is a highly selective next-generation anaplastic lymphoma kinase (ALK) inhibitor. Although alectinib shows inhibitory activity against various crizotinib-resistant ALK mutations in studies using cell-free kinase assays and Ba/F3 cell-based assays, it has not been tested for efficacy against non-small cell lung cancer (NSCLC) with the ALK mutations. We conducted in vitro and in vivo investigations into the antitumor activity of alectinib against an ALK-positive NSCLC cell line, SNU-2535, which harbors an ALK G1269A mutation. The clinical efficacy of alectinib against a NSCLC patient harboring ALK G1269A mutation was evaluated in the phase I part of the North American study. Alectinib exhibited antiproliferative activity against SNU-2535 cells in vitro with IC50 of 33.1 nM. Alectinib strongly inhibited phosphorylation of ALK and its downstream signaling molecules ERK1/2, AKT, and STAT3. In a mouse xenograft model, once-daily oral administration of alectinib for 21 days resulted in strong tumor regression. In addition, administration of alectinib for 100 days achieved continuous tumor regression without tumor regrowth in all mice. Notably, eradication of tumor cells was observed in half of the mice. In the clinical study, a patient with ALK G1269A mutation showed partial response to alectinib with a duration of response of 84 days. These results indicated that alectinib has potent antitumor activity against NSCLC cells harboring the crizotinib-resistant mutation ALK G1269A. It is expected that alectinib would provide a valuable therapeutic option for patients with NSCLC having not only native ALK but also crizotinib-resistant ALK mutations.

  15. Comparison of amine-selective properties of weak and strong cation-exchangers.

    PubMed

    Stenholm, Ake; Lindgren, Helena; Shaffie, Juliana

    2006-09-22

    The capacity of several weak and strong cation-exchangers to adsorb 2-diethylaminoethanol (DEAE) and (2,3-hydroxypropyl) trimethylammonium chloride (HPMAC) from sodium-containing process water streams, and the ease of subsequently eluting the amines and regenerating the exchangers, were investigated. (2,3-hydroxypropyl) trimethylammonium chloride was enriched 40-fold compared with the initial amine/sodium-ratio in the bulk fluid by Amberlite IRC-50. The highest selectivity for 2-diethylaminoethanol (26-fold) was provided by Imac HP336. Neither of the selected strong cation-exchangers showed any selectivity towards 2-diethylaminoethanol, but they enriched (2,3-hydroxypropyl) trimethylammonium chloride approximately three to four fold. These findings suggest that weak cation-exchangers (WCX) could be readily used for the selective removal of these or similar amines from sodium-containing process waters.

  16. Altered Ca2+ Kinetics Associated with α-Actinin-3 Deficiency May Explain Positive Selection for ACTN3 Null Allele in Human Evolution

    PubMed Central

    Houweling, Peter J.; Quinlan, Kate G. R.; Murphy, Robyn; Wagner, Sören; Friedrich, Oliver; North, Kathryn N.

    2015-01-01

    Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more “energy efficient” in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i) an increased rate of decay of the twitch transient; (ii) a fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments during recent evolution. PMID:25590636

  17. The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy

    PubMed Central

    Zhang, Ning-Ning; Liu, Yu-Tao; Ma, Li; Wang, Lin; Hao, Xue-Zhi; Yuan, Zheng; Lin, Dong-Mei; Li, Dan; Zhou, Yu-Jie; Lin, Hua; Han, Xiao-Hong; Sun, Yan; Shi, Yuankai

    2014-01-01

    Background This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. PMID:24404167

  18. Predicting factors of positive orientation and attitudes towards nursing: A quantitative cross-sectional study.

    PubMed

    Ten Hoeve, Yvonne; Castelein, Stynke; Jansen, Wiebren; Jansen, Gerard; Roodbol, Petrie

    2016-05-01

    Previous studies have identified various reasons for students to choose a career in nursing. Students at the start of their programme hold a great variety of images and perceptions of nursing which can affect their orientation and attitudes towards their future profession. This paper aims to examine nursing students' orientation and attitudes towards nursing at the beginning of their educational programme, and to explore predictors of positive orientation and attitudes. The study used a quantitative cross-sectional design. A survey was conducted among first-year nursing students at four nursing universities of applied sciences in the Netherlands. Questionnaires were administered to all students enrolled in a bachelor of nursing programme (n=1414) at these universities. Respondents completed a survey consisting of: 1) Nursing Orientation Tool, 2) Nursing Attitude Questionnaire, and 3) demographic data such as gender, living status, nursing experience, preliminary training, first-choice programme, and career choice. Kruskal Wallis tests, with post hoc Mann Whitney U tests, were used to compare group scores. Multiple regression was performed to investigate predictors of positive orientation and attitudes towards nursing. Students in this study sample (n=1244) strongly agreed with statements related to caring, nursing expertise, professional nursing knowledge and the application of this knowledge. Predictors of positive orientation and attitudes towards nursing include having nursing/caring experience, indicating nursing as the first choice for study, preliminary vocational training, and a desire to make a career in nursing. Data from this survey suggest a link between personal and environmental characteristics and motivations to select nursing as a career. Understanding which factors predict positive orientation and attitudes towards nursing could offer educators a tool in the recruitment and selection assessment of new students. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Highly Selective Coupling of Alkenes and Aldehydes Catalyzed by NHC–Ni–P(OPh)3: Synergy Between a Strong σ-Donor and a Strong π-Acceptor**

    PubMed Central

    Ho, Chun-Yu; Jamison, Timothy F.

    2011-01-01

    Both a strong electron donor (IPr) and a strong electron acceptor (P(OPh)3) are necessary for a highly selective, nickel-catalyzed coupling reaction between alkenes, aldehydes, and silyltriflates. Without the phosphite, catalysis is not observed and several side reactions are observed. The phosphite appears to suppress the formation of these byproducts and rescue the catalytic cycle by accelerating reductive elimination from an (IPr–Ni–H)(OTf) complex. PMID:17154217

  20. Male reproductive fitness and queen polyandry are linked to variation in the supergene Gp-9 in the fire ant Solenopsis invicta.

    PubMed

    Lawson, Lucinda P; Vander Meer, Robert K; Shoemaker, Dewayne

    2012-08-22

    Supergenes are clusters of tightly linked loci maintained in specific allelic combinations to facilitate co-segregation of genes governing adaptive phenotypes. In species where strong selection potentially operates at different levels (e.g. eusocial Hymenoptera), positive selection acting within a population to maintain specific allelic combinations in supergenes may have unexpected consequences for some individuals, including the preservation of disadvantageous traits. The nuclear gene Gp-9 in the invasive fire ant Solenopsis invicta is part of a non-recombining, polymorphic supergene region associated with polymorphism in social organization as well as traits affecting physiology, fecundity and behaviour. We show that both male reproductive success and facultative polyandry in queens have a simple genetic basis and are dependent on male Gp-9 genotype. Gp-9(b) males are unable to maintain exclusive reproductive control over their mates such that queens mated to Gp-9(b) males remain highly receptive to remating. Queens mated to multiple Gp-9(B) males are rare. This difference appears to be independent of mating plug production in fertile males of each Gp-9 genotype. However, Gp-9(b) males have significantly lower sperm counts than Gp-9(B) males, which could be a cue to females to seek additional mates. Despite the reduced fitness of Gp-9(b) males, polygyne worker-induced selective mortality of sexuals lacking b-like alleles coupled with the overall success of the polygyne social form act to maintain the Gp-9(b) allele within nature. Our findings highlight how strong worker-induced selection acting to maintain the Gp-9(b) allele in the polygyne social form may simultaneously result in reduced reproductive fitness for individual sexual offspring.

  1. The origins of lactase persistence in Europe.

    PubMed

    Itan, Yuval; Powell, Adam; Beaumont, Mark A; Burger, Joachim; Thomas, Mark G

    2009-08-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

  2. The Origins of Lactase Persistence in Europe

    PubMed Central

    Itan, Yuval; Powell, Adam; Beaumont, Mark A.; Burger, Joachim; Thomas, Mark G.

    2009-01-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe. PMID:19714206

  3. Male reproductive fitness and queen polyandry are linked to variation in the supergene Gp-9 in the fire ant Solenopsis invicta

    PubMed Central

    Lawson, Lucinda P.; Vander Meer, Robert K.; Shoemaker, DeWayne

    2012-01-01

    Supergenes are clusters of tightly linked loci maintained in specific allelic combinations to facilitate co-segregation of genes governing adaptive phenotypes. In species where strong selection potentially operates at different levels (e.g. eusocial Hymenoptera), positive selection acting within a population to maintain specific allelic combinations in supergenes may have unexpected consequences for some individuals, including the preservation of disadvantageous traits. The nuclear gene Gp-9 in the invasive fire ant Solenopsis invicta is part of a non-recombining, polymorphic supergene region associated with polymorphism in social organization as well as traits affecting physiology, fecundity and behaviour. We show that both male reproductive success and facultative polyandry in queens have a simple genetic basis and are dependent on male Gp-9 genotype. Gp-9b males are unable to maintain exclusive reproductive control over their mates such that queens mated to Gp-9b males remain highly receptive to remating. Queens mated to multiple Gp-9B males are rare. This difference appears to be independent of mating plug production in fertile males of each Gp-9 genotype. However, Gp-9b males have significantly lower sperm counts than Gp-9B males, which could be a cue to females to seek additional mates. Despite the reduced fitness of Gp-9b males, polygyne worker-induced selective mortality of sexuals lacking b-like alleles coupled with the overall success of the polygyne social form act to maintain the Gp-9b allele within nature. Our findings highlight how strong worker-induced selection acting to maintain the Gp-9b allele in the polygyne social form may simultaneously result in reduced reproductive fitness for individual sexual offspring. PMID:22535783

  4. Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14*

    PubMed Central

    Zou, Haiyin; Wu, Ying

    2016-01-01

    The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains (NTIMPs) is consistent with the previous isothermal titration calorimetric finding that their interactions are entropy-driven but differ in contributions from solvent and conformational entropy (ΔSsolv, ΔSconf), estimated using heat capacity changes (ΔCp). Selective engineered NTIMPs have potential applications for treating MMP-related diseases, including cancer and cardiomyopathy. Here we report isothermal titration calorimetric studies of the effects of selectivity-modifying mutations in NTIMP1 and NTIMP2 on the thermodynamics of their interactions with MMP1, MMP3, and MMP14. The weak inhibition of MMP14 by NTIMP1 reflects a large conformational entropy penalty for binding. The T98L mutation, peripheral to the NTIMP1 reactive site, enhances binding by increasing ΔSsolv but also reduces ΔSconf. However, the same mutation increases NTIMP1 binding to MMP3 in an interaction that has an unusual positive ΔCp. This indicates a decrease in solvent entropy compensated by increased conformational entropy, possibly reflecting interactions involving alternative conformers. The NTIMP2 mutant, S2D/S4A is a selective MMP1 inhibitor through electrostatic effects of a unique MMP-1 arginine. Asp-2 increases reactive site polarity, reducing ΔCp, but increases conformational entropy to maintain strong binding to MMP1. There is a strong negative correlation between ΔSsolv and ΔSconf for all characterized interactions, but the data for each MMP have characteristic ranges, reflecting intrinsic differences in the structures and dynamics of their free and inhibitor-bound forms. PMID:27033700

  5. Optimizing trial design in pharmacogenetics research: comparing a fixed parallel group, group sequential, and adaptive selection design on sample size requirements.

    PubMed

    Boessen, Ruud; van der Baan, Frederieke; Groenwold, Rolf; Egberts, Antoine; Klungel, Olaf; Grobbee, Diederick; Knol, Mirjam; Roes, Kit

    2013-01-01

    Two-stage clinical trial designs may be efficient in pharmacogenetics research when there is some but inconclusive evidence of effect modification by a genomic marker. Two-stage designs allow to stop early for efficacy or futility and can offer the additional opportunity to enrich the study population to a specific patient subgroup after an interim analysis. This study compared sample size requirements for fixed parallel group, group sequential, and adaptive selection designs with equal overall power and control of the family-wise type I error rate. The designs were evaluated across scenarios that defined the effect sizes in the marker positive and marker negative subgroups and the prevalence of marker positive patients in the overall study population. Effect sizes were chosen to reflect realistic planning scenarios, where at least some effect is present in the marker negative subgroup. In addition, scenarios were considered in which the assumed 'true' subgroup effects (i.e., the postulated effects) differed from those hypothesized at the planning stage. As expected, both two-stage designs generally required fewer patients than a fixed parallel group design, and the advantage increased as the difference between subgroups increased. The adaptive selection design added little further reduction in sample size, as compared with the group sequential design, when the postulated effect sizes were equal to those hypothesized at the planning stage. However, when the postulated effects deviated strongly in favor of enrichment, the comparative advantage of the adaptive selection design increased, which precisely reflects the adaptive nature of the design. Copyright © 2013 John Wiley & Sons, Ltd.

  6. An exceptionally preserved armored dinosaur reveals the morphology and allometry of osteoderms and their horny epidermal coverings.

    PubMed

    Brown, Caleb M

    2017-01-01

    Although the evolution and function of "exaggerated" bony projections in ornithischian dinosaurs has been subject to significant debate recently, our understanding of the structure and morphology of their epidermal keratinized coverings is greatly limited. The holotype of Borealopelta , a new nodosaurid ankylosaur, preserves osteoderms and extensive epidermal structures (dark organic residues), in anatomic position across the entire precaudal length. Contrasting previous specimens, organic epiosteodermal scales, often in the form of horn-like (keratinous) sheaths, cap and exaggerate nearly all osteoderms, allowing for morphometric and allometric analyses of both the bony osteoderms and their horny sheaths. A total of 172 osteoderms were quantified, with osteoderm spine length and height being positively allometric with respect to basal length and width. Despite tight correlations between the different measures amongst all other osteoderms, the large parascapular spines represent consistent outliers. Thickness and relative contribution of the keratinized epiosteodermal scales/sheaths varies greatly by region, ranging from 2% to 6% for posterior thoracics, to ∼25% (1.3×) for the parascapular spines-similar to horn sheaths in some bovid analogues. Relative to the bony cores, the horny portions of the spines are strongly positively allometric (slope = 2.3, CI = 1.8-2.8). Strong allometric scaling, species-specific morphology, and significant keratinous extension of the cervicoscapular spines is consistent with elaboration under socio-sexual selection. This marks the first allometric analysis of ornithischian soft tissues.

  7. The Tooth and Skin Colour Interrelationship across the Different Ethnic Groups

    PubMed Central

    Haralur, Satheesh B.; Dibas, Ahmed Mohammed; Almelhi, Nabil Abdullah; Al-Qahtani, Dhafer Ali

    2014-01-01

    Objectives. The purpose of the study was to investigate the relation between skin and tooth colour parameters in various ethnic groups. Materials and Methods. Saudi Arabian, Indian, African, and East Asian ethnic groups of 75 each were included in the study. The tooth colour was determined by spectrophotometer in CIELAB parameters. The skin colour was measured at earlobe, forehead, and malar locations by clinical skin photography. The data was statistically analysed by one-way ANOVA and correlation tests. Results. The “L” vale for the Saudi Arabian group had a strong correlation at earlobe location (r = 0.275), while correlation was found at forehead (r = 0.271) and malar region (r = 0.261) with Indian ethnic group. A strong negative correlation was observed in African ethnic group at all three locations for “L” parameter. The redness value “a” is found to have strong negative linear correlation between the earlobe and tooth for Saudi Arabian (r = −0.240) and Indian ethnic groups (r = −0.268). The “b” showed no correlation with skin location in all groups except positive correlation in African ethnic groups. Conclusions. The strong correlation was found between the skin and tooth colour parameters; hence the skin colour can be used as a guide for artificial tooth selection in edentulous patients. PMID:25101125

  8. The Tooth and Skin Colour Interrelationship across the Different Ethnic Groups.

    PubMed

    Haralur, Satheesh B; Dibas, Ahmed Mohammed; Almelhi, Nabil Abdullah; Al-Qahtani, Dhafer Ali

    2014-01-01

    Objectives. The purpose of the study was to investigate the relation between skin and tooth colour parameters in various ethnic groups. Materials and Methods. Saudi Arabian, Indian, African, and East Asian ethnic groups of 75 each were included in the study. The tooth colour was determined by spectrophotometer in CIELAB parameters. The skin colour was measured at earlobe, forehead, and malar locations by clinical skin photography. The data was statistically analysed by one-way ANOVA and correlation tests. Results. The "L" vale for the Saudi Arabian group had a strong correlation at earlobe location (r = 0.275), while correlation was found at forehead (r = 0.271) and malar region (r = 0.261) with Indian ethnic group. A strong negative correlation was observed in African ethnic group at all three locations for "L" parameter. The redness value "a" is found to have strong negative linear correlation between the earlobe and tooth for Saudi Arabian (r = -0.240) and Indian ethnic groups (r = -0.268). The "b" showed no correlation with skin location in all groups except positive correlation in African ethnic groups. Conclusions. The strong correlation was found between the skin and tooth colour parameters; hence the skin colour can be used as a guide for artificial tooth selection in edentulous patients.

  9. Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population

    PubMed Central

    Bolund, Elisabeth; Bouwhuis, Sandra; Pettay, Jenni E.; Lummaa, Virpi

    2013-01-01

    The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution. PMID:24107531

  10. Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population.

    PubMed

    Bolund, Elisabeth; Bouwhuis, Sandra; Pettay, Jenni E; Lummaa, Virpi

    2013-12-07

    The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution.

  11. Habitat selection by breeding waterbirds at ponds with size-structured fish populations

    NASA Astrophysics Data System (ADS)

    Kloskowski, Janusz; Nieoczym, Marek; Polak, Marcin; Pitucha, Piotr

    2010-07-01

    Fish may significantly affect habitat use by birds, either as their prey or as competitors. Fish communities are often distinctly size-structured, but the consequences for waterbird assemblages remain poorly understood. We examined the effects of size structure of common carp ( Cyprinus carpio) cohorts together with other biotic and abiotic pond characteristics on the distribution of breeding waterbirds in a seminatural system of monocultured ponds, where three fish age classes were separately stocked. Fish age corresponded to a distinct fish size gradient. Fish age and total biomass, macroinvertebrate and amphibian abundance, and emergent vegetation best explained the differences in bird density between ponds. Abundance of animal prey other than fish (aquatic macroinvertebrates and larval amphibians) decreased with increasing carp age in the ponds. Densities of ducks and smaller grebes were strongly negatively associated with fish age/size gradient. The largest of the grebes, the piscivorous great crested grebe ( Podiceps cristatus), was the only species that preferred ponds with medium-sized fish and was positively associated with total fish biomass. Habitat selection by bitterns and most rallids was instead strongly influenced by the relative amount of emergent vegetation cover in the ponds. Our results show that fish size structure may be an important cue for breeding habitat choice and a factor affording an opportunity for niche diversification in avian communities.

  12. α-Eleostearic acid-containing triglycerides for a continuous assay to determine lipase sn-1 and sn-3 regio-preference.

    PubMed

    El Alaoui, Meddy; Soulère, Laurent; Noiriel, Alexandre; Queneau, Yves; Abousalham, Abdelkarim

    2017-08-01

    Lipases are essentially described as sn-1 and sn-3 regio-selective. Actually few methods are available to measure this lipase regio-selectivity, moreover they require chiral chromatography analysis or specific derivations which are discontinuous and time consuming. In this study we describe a new, convenient, sensitive and continuous spectrophotometric method to screen lipases regio-selectivity using synthetic triglycerides (TG) containing α-eleostearic acid (9Z, 11E, 13E-octadecatrienoic acid) either at the sn-1 position [1-α-eleostearoyl-2,3-octadecyl-sn-glycerol (sn-EOO)] or at the sn-3 position [1,2-octadecyl-3-α-eleostearoyl-sn-glycerol (sn-OOE)] and coated onto the wells of microtiter plates. A non-hydrolysable ether bond, with a non UV-absorbing alkyl chain, was introduced at the other sn positions to prevent acyl chain migration during TG synthesis or lipolysis. The synthesis of TG containing α-eleostearic acid was performed from S-glycidol in six steps to obtain sn-EOO and in five steps to sn-OOE. The α-eleostearic acid conjugated triene constitutes an intrinsic chromophore and, consequently, confers the strong UV absorption properties of this free fatty acid as well as of the TG harboring it. The lipase activity on coated sn-EOO or sn-OOE was measured by the increase in the absorbance at 272nm due to the transition of α-eleostearic acid from the adsorbed to the soluble state. Human and porcine pancreatic lipases, guinea pig pancreatic lipase related protein 2, Thermomyces lanuginosus lipase, Candida antarctica lipase A and Candida antarctica lipase B were all used to validate the assay. This continuous high-throughput screening method could determine directly without any processes after lipolysis the regio-selectivity of various lipases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Epidemiological survey of brucellosis in sheep and goats in selected pastoral and agro-pastoral lowlands of Ethiopia.

    PubMed

    Sintayehu, G; Melesse, B; Abayneh, D; Sintayehu, A; Melaku, S; Alehegne, W; Mesfin, S; De Blas, I; Casal, J; Allepuz, A; Martin-Valls, G; Africa, T; Abera, K

    2015-12-01

    An epidemiological survey was conducted in pastoral regions of Ethiopia to investigate the distribution of brucellosis in sheep and goats. Between November 2004 and December 2007, a total of 6,201 serum samples were collected from 67 randomly selected peasant associations, 25 districts and eight pastoral zones of Ethiopia. The Rose Bengal plate test (RBPT) and complement fixation test were used in series. Samples for bacteriology were collected from three export abattoirs, where 285 goats were randomly selected and tested by RBPTthree days before slaughter. Tissue samples were collected from 14 strongly positive goats and cultured in dextrose agar and Brucella agar base. To confirm and subtype the isolates, staining, biochemical tests and polymerase chain reaction were used. The overall standardised seroprevalence of brucellosis was 1.9%, ranging from 0.07% in Jijiga zone to 3.3% in Borena zone. There was statistically significant variation among the studied regions, zones, districts and peasant associations (p < 0.05). Male goats and sheep were twice as likely to test positive as females (relative risk [RRJ: 2.04; 95% confidence interval [CI]:1.7-3.4; x2 = 21.05, p < 0.05). Adults (older than 1.5 years) were three times more likely to test positive than younger animals (RR: 2.76; 95% CI: 1.14-6.73; chi2 = 5.18, p < 0.05). Goats were around four times more likely to be infected than sheep (RR: 3.8; 95% CI: 2.4-6.1; chi2 = 36.99, p < 0.05). Brucella melitensis was isolated from 2 of the 14 samples analysed. The widespread distribution of brucellosis in goats and sheep in these areas justifies the use of control measures to minimise the economic losses and public health hazards.

  14. Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection

    PubMed Central

    Cornejo, Omar E.; Durrego, Ester; Stanley, Craig E.; Castillo, Andreína I.; Herrera, Sócrates; Escalante, Ananias A.

    2016-01-01

    Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

  15. Ancient DNA Investigation of a Medieval German Cemetery Confirms Long-Term Stability of CCR5-Δ32 Allele Frequencies in Central Europe.

    PubMed

    Bouwman, Abigail; Shved, Natallia; Akgül, Gülfirde; Rühli, Frank; Warinner, Christina

    2017-04-01

    The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.

  16. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review.

    PubMed

    Jameera Begam, A; Jubie, S; Nanjan, M J

    2017-04-01

    Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer. Keeping this in view, the present review focuses on selective estrogen receptor modulators and estrogen antagonists such as sulfatase and aromatase inhibitors involved in breast cancer therapy. A succinct and critical overview of the structure of estrogen receptors, their signaling and involvement in breast carcinogenesis are herein described. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Deontic reasoning as a target of selection: reply to Astington and Dack.

    PubMed

    Cummins, Denise Dellarosa

    2013-12-01

    In their discussion of young children's deontic reasoning performance, Astington and Dack (2013) made the following claims: (1) Children need more cues to elicit cogent social norm reasoning than adults require, namely, explicit reference to authority; (2) Deontic reasoning improves with age, and this is evidence against a nativist view; (3) All evolutionary explanations of deontic reasoning advantages require positing a ''domain-specific deontic reasoning module."; and (4) young children excel at deontic reasoning because it is easier. Here, I refute each claim. Instead, I argue that (1) Social norm reasoning is one type of deontic reasoning that has been the target of selective pressure; (2) Development does not preclude nativism; (3) Epistemic utterances make no greater processing demands than deontic utterances; and (4) both adult and child norm reasoning performance is strongly influenced by reference to or implication of authority. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Probing the Selectivity and Protein•Protein Interactions of a Non-Reducing Fungal Polyketide Synthase Using Mechanism-Based Crosslinkers

    PubMed Central

    Bruegger, Joel; Haushalter, Bob; Vagstad, Anna; Shakya, Gaurav; Mih, Nathan; Townsend, Craig A.; Burkart, Michael D.; Tsai, Shiou-Chuan

    2013-01-01

    SUMMARY Protein•protein interactions, which often involve interactions between an acyl carrier protein (ACP) and its partner enzymes, are important for coordinating polyketide biosynthesis. However, the nature of such interactions is not well understood, especially in the fungal non-reducing polyketide synthases (NR-PKSs) that biosynthesize toxic and pharmaceutically important polyketides. Here, we employ a mechanism-based crosslinker to successfully probe ACP and ketosynthase (KS) domain interactions in NR-PKSs. We found that crosslinking efficiency is closely correlated with the strength of ACP•KS interactions, and that KS demonstrates strong starter unit selectivity. We further identified positively charged surface residues by KS mutagenesis, which mediate key interactions with the negatively-charged ACP surface. Such complementary/matching contact pairs can serve as “adapter surfaces” for future efforts to generate new polyketides using NR-PKSs. PMID:23993461

  19. Global dynamics of selective attention and its lapses in primary auditory cortex.

    PubMed

    Lakatos, Peter; Barczak, Annamaria; Neymotin, Samuel A; McGinnis, Tammy; Ross, Deborah; Javitt, Daniel C; O'Connell, Monica Noelle

    2016-12-01

    Previous research demonstrated that while selectively attending to relevant aspects of the external world, the brain extracts pertinent information by aligning its neuronal oscillations to key time points of stimuli or their sampling by sensory organs. This alignment mechanism is termed oscillatory entrainment. We investigated the global, long-timescale dynamics of this mechanism in the primary auditory cortex of nonhuman primates, and hypothesized that lapses of entrainment would correspond to lapses of attention. By examining electrophysiological and behavioral measures, we observed that besides the lack of entrainment by external stimuli, attentional lapses were also characterized by high-amplitude alpha oscillations, with alpha frequency structuring of neuronal ensemble and single-unit operations. Entrainment and alpha-oscillation-dominated periods were strongly anticorrelated and fluctuated rhythmically at an ultra-slow rate. Our results indicate that these two distinct brain states represent externally versus internally oriented computational resources engaged by large-scale task-positive and task-negative functional networks.

  20. In silico selection of therapeutic antibodies for development: Viscosity, clearance, and chemical stability

    PubMed Central

    Sharma, Vikas K.; Patapoff, Thomas W.; Kabakoff, Bruce; Pai, Satyan; Hilario, Eric; Zhang, Boyan; Li, Charlene; Borisov, Oleg; Kelley, Robert F.; Chorny, Ilya; Zhou, Joe Z.; Dill, Ken A.; Swartz, Trevor E.

    2014-01-01

    For mAbs to be viable therapeutics, they must be formulated to have low viscosity, be chemically stable, and have normal in vivo clearance rates. We explored these properties by observing correlations of up to 60 different antibodies of the IgG1 isotype. Unexpectedly, we observe significant correlations with simple physical properties obtainable from antibody sequences and by molecular dynamics simulations of individual antibody molecules. mAbs viscosities increase strongly with hydrophobicity and charge dipole distribution and decrease with net charge. Fast clearance correlates with high hydrophobicities of certain complementarity determining regions and with high positive or high negative net charge. Chemical degradation from tryptophan oxidation correlates with the average solvent exposure time of tryptophan residues. Aspartic acid isomerization rates can be predicted from solvent exposure and flexibility as determined by molecular dynamics simulations. These studies should aid in more rapid screening and selection of mAb candidates during early discovery. PMID:25512516

  1. Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell.

    PubMed

    Bennekou, Poul; Barksmann, Trine L; Jensen, Lars R; Kristensen, Berit I; Christophersen, Palle

    2004-05-01

    Suspension of intact human red cells in media with low chloride and sodium concentrations (isotonic sucrose substitution) results in strongly inside positive membrane potentials, which activate the voltage-dependent non-selective cation (NSVDC) channel. By systematic variation of the initial Nernst potentials for chloride (degree of ion substitution) as well as the chloride conductance (block by NS1652), and by exploiting the interplay between the Ca(2+)-permeable NSVDC channel, the Ca(2+)-activated K+ channel (the Gárdos channel) and the Ca(2+)-pump, a graded activation of the NSVDC channel was achieved. Under these conditions, it was shown that the NSVDC channels exist in two states of activation depending on the initial conditions for the activation. The hysteretic behaviour, which in patch clamp experiments has been found for the individual channel unit, is thus retained at the cellular level and can be demonstrated with red cells in suspension.

  2. Poly(ionic liquid) based chemosensors for detection of basic amino acids in aqueous medium

    NASA Astrophysics Data System (ADS)

    Li, Xinjuan; Wang, Kai; Ma, Nana; Jia, Xianbin

    2017-09-01

    Naked-eye detection of amino acids in water is of great significance in the field of bio-analytical applications. Herein, polymerized ionic liquids (PILs) with controlled chain length structures were synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization and post-quaternization approach. The amino acids recognition performance of PILs with different alkyl chain lengths and molecular weights was evaluated by naked-eye color change and ultraviolet-visible (UV-vis) spectral studies. These PILs were successfully used for highly sensitive and selective detection of Arg, Lys and His in water. The recognition performance was improved effectively with increased molecular weight of PILs. The biosensitivity of the PILs in water was strongly dependent on their aggregation effect and polarization effect. Highly sensitive and selective detection of amino acids was successfully accomplished by introducing positively charged pyridinium moieties and controlled RAFT radical polymerization.

  3. Stabilizing selection on sperm number revealed by artificial selection and experimental evolution.

    PubMed

    Cattelan, Silvia; Di Nisio, Andrea; Pilastro, Andrea

    2018-03-01

    Sperm competition is taxonomically widespread in animals and is usually associated with large sperm production, being the number of sperm in the competing pool the prime predictor of fertilization success. Despite the strong postcopulatory selection acting directionally on sperm production, its genetic variance is often very high. This can be explained by trade-offs between sperm production and traits associated with mate acquisition or survival, that may contribute to generate an overall stabilizing selection. To investigate this hypothesis, we first artificially selected male guppies (Poecilia reticulata) for high and low sperm production for three generations, while simultaneously removing sexual selection. Then, we interrupted artificial selection and restored sexual selection. Sperm production responded to divergent selection in one generation, and when we restored sexual selection, both high and low lines converged back to the mean sperm production of the original population within two generations, indicating that sperm number is subject to strong stabilizing total sexual selection (i.e., selection acting simultaneously on all traits associated with reproductive success). We discuss the possible mechanisms responsible for the maintenance of high genetic variability in sperm production despite strong selection acting on it. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  4. The typical RB76 recombination breakpoint of the invasive recombinant tomato yellow leaf curl virus of Morocco can be generated experimentally but is not positively selected in tomato.

    PubMed

    Belabess, Z; Urbino, C; Granier, M; Tahiri, A; Blenzar, A; Peterschmitt, M

    2018-01-02

    TYLCV-IS76 is an unusual recombinant between the highly recombinogenic tomato yellow leaf curl virus (TYLCV) and tomato yellow leaf curl Sardinia virus (TYLCSV), two Mediterranean begomoviruses (Geminiviridae). In contrast with the previously reported TYLCV/TYLCSV recombinants, it has a TYLCSV derived fragment of only 76 nucleotides, and has replaced its parental viruses in natural conditions (Morocco, Souss region). The viral population shift coincided with the deployment of the popular Ty-1 resistant tomato cultivars, and according to experimental studies, has been driven by a strong positive selection in such resistant plants. However, although Ty-1 cultivars were extensively used in Mediterranean countries, TYLCV-IS76 was not reported outside Morocco. This, in combination with its unusual recombination pattern suggests that it was generated through a rare and possibly multistep process. The potential generation of a recombination breakpoint (RB) at locus 76 (RB76) was investigated over time in 10 Ty-1 resistant and 10 nearly isogenic susceptible tomato plants co-inoculated with TYLCV and TYLCSV clones. RB76 could not be detected in the recombinant progeny using the standard PCR/sequencing approach that was previously designed to monitor the emergence of TYLCV-IS76 in Morocco. Using a more sensitive PCR test, RB76 was detected in one resistant and five susceptible plants. The results are consistent with a very low intra-plant frequency of RB76 bearing recombinants throughout the test and support the hypothesis of a rare emergence of TYLCV-IS76. More generally, RBs were more scattered in resistant than in susceptible plants and an unusual RB at position 141 (RB141) was positively selected in the resistant cultivar; interestingly, RB141 bearing recombinants were detected in resistant tomato plants from the field. Scenarios of TYLCV-IS76 pre-emergence are proposed. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The dynamics of diverse segmental amplifications in populations of Saccharomyces cerevisiae adapting to strong selection.

    PubMed

    Payen, Celia; Di Rienzi, Sara C; Ong, Giang T; Pogachar, Jamie L; Sanchez, Joseph C; Sunshine, Anna B; Raghuraman, M K; Brewer, Bonita J; Dunham, Maitreya J

    2014-03-20

    Population adaptation to strong selection can occur through the sequential or parallel accumulation of competing beneficial mutations. The dynamics, diversity, and rate of fixation of beneficial mutations within and between populations are still poorly understood. To study how the mutational landscape varies across populations during adaptation, we performed experimental evolution on seven parallel populations of Saccharomyces cerevisiae continuously cultured in limiting sulfate medium. By combining quantitative polymerase chain reaction, array comparative genomic hybridization, restriction digestion and contour-clamped homogeneous electric field gel electrophoresis, and whole-genome sequencing, we followed the trajectory of evolution to determine the identity and fate of beneficial mutations. During a period of 200 generations, the yeast populations displayed parallel evolutionary dynamics that were driven by the coexistence of independent beneficial mutations. Selective amplifications rapidly evolved under this selection pressure, in particular common inverted amplifications containing the sulfate transporter gene SUL1. Compared with single clones, detailed analysis of the populations uncovers a greater complexity whereby multiple subpopulations arise and compete despite a strong selection. The most common evolutionary adaptation to strong selection in these populations grown in sulfate limitation is determined by clonal interference, with adaptive variants both persisting and replacing one another.

  6. The Dynamics of Diverse Segmental Amplifications in Populations of Saccharomyces cerevisiae Adapting to Strong Selection

    PubMed Central

    Payen, Celia; Di Rienzi, Sara C.; Ong, Giang T.; Pogachar, Jamie L.; Sanchez, Joseph C.; Sunshine, Anna B.; Raghuraman, M. K.; Brewer, Bonita J.; Dunham, Maitreya J.

    2014-01-01

    Population adaptation to strong selection can occur through the sequential or parallel accumulation of competing beneficial mutations. The dynamics, diversity, and rate of fixation of beneficial mutations within and between populations are still poorly understood. To study how the mutational landscape varies across populations during adaptation, we performed experimental evolution on seven parallel populations of Saccharomyces cerevisiae continuously cultured in limiting sulfate medium. By combining quantitative polymerase chain reaction, array comparative genomic hybridization, restriction digestion and contour-clamped homogeneous electric field gel electrophoresis, and whole-genome sequencing, we followed the trajectory of evolution to determine the identity and fate of beneficial mutations. During a period of 200 generations, the yeast populations displayed parallel evolutionary dynamics that were driven by the coexistence of independent beneficial mutations. Selective amplifications rapidly evolved under this selection pressure, in particular common inverted amplifications containing the sulfate transporter gene SUL1. Compared with single clones, detailed analysis of the populations uncovers a greater complexity whereby multiple subpopulations arise and compete despite a strong selection. The most common evolutionary adaptation to strong selection in these populations grown in sulfate limitation is determined by clonal interference, with adaptive variants both persisting and replacing one another. PMID:24368781

  7. Specialized proteasome subunits play an essential role in thymic selection of CD8+ T cells

    PubMed Central

    Kincaid, Eleanor Z.; Murata, Shigeo; Tanaka, Keiji; Rock, Kenneth L.

    2016-01-01

    The cells that stimulate positive selection express different specialized proteasome β-subunits than all other cells, including those involved in negative selection. Mice that lack all four specialized proteasome β-subunits, and therefore express only constitutive proteasomes in all cells, had a profound defect in the generation of CD8+ T cells. While a defect in positive selection would reflect an inability to generate the appropriate positively selecting peptides, a block at negative selection would point to the potential need to switch peptides between positive and negative selection to avoid the two processes often cancelling each other out. We found that the block in T cell development occurred around the checkpoints of positive and, surprisingly, also negative selection. PMID:27294792

  8. Biconditional Prominence Correlation

    ERIC Educational Resources Information Center

    Teeple, David Allan

    2009-01-01

    This dissertation presents one solution to a problem in phonological typology, which is to explain the apparent cross-linguistic absence of a pattern I call "Strong-Position Neutralization" (or SPN): neutralization of a contrast in a strong position while the same contrast is maintained in the corresponding weak position. This is predicted in a…

  9. Advancing the pharmacy practice research agenda: views and experiences of pharmacists in Qatar.

    PubMed

    Elkassem, Wessam; Pallivalapila, Abdulrouf; Al Hail, Moza; McHattie, Lorna; Diack, Lesley; Stewart, Derek

    2013-10-01

    There is little emphasis on pharmacy practice research in Qatar, with a lack of relevant education and training and a notable lack of exposure to processes of research. To describe views and attitudes of pharmacists in Qatar to pharmacy practice research prior to and following a 2 day introductory research workshop. All pharmacists (n = 350) were invited to express interest in attending. All participants were required to complete a questionnaire covering views and attitudes relating to research. Workshop sessions were on: research questions; critically appraising literature; developing research methods; collecting and analysing data; and disseminating findings. Participants completed a post-course evaluation questionnaire. Of the ninety expressing interest, 47 were selected and participated in the first training day, with 40 of these also attending the second day. Participants expressed positive views and attitudes towards research. Most (46/47) strongly agreed/agreed that it was their professional duty to be involved; all strongly agreed/agreed with importance of an evidence base to support practice; but there were issues around time, support and training. The research workshops were positively evaluated by participants. Findings indicate pharmacists' willingness to participate in research training in Qatar. However, there is a need to ensure that views and attitudes translate into research participation thus enhancing the evidence base.

  10. Effects of Carcass Weight and Back-fat Thickness on Carcass Properties of Korean Native Pigs.

    PubMed

    Kim, Gye-Woong; Kim, Hack-Youn

    2017-01-01

    Our study analyzed the carcass properties of 170 Korean native pigs in relation to carcass weight and back-fat thickness to provide general data for the production and distribution of high quality pig meat. The 70-74 kg group showed highest yield (73.41%). The ≥80 kg group showed the highest thickest back-fat (24.13 mm) ( p <0.05). The ≥80 kg group showed the best quality grade (1.00). Back-fat thickness showed significant differences in the weight among groups ( p <0.05). The ≥25 mm group showed the highest carcass weight (75.93 kg). The thickest back-fat group (≥25 mm) showed the highest yield (73.03%). There were significant differences in back-fat thickness among groups ( p <0.05), and the ≥25 mm group showed the highest thickness back-fat (27.60 mm). We found a strong positive correlation between carcass weight and back-fat thickness (r=0.346) as well as meat quality grade (r=0.739). Back-fat thickness had a relatively strong positive correlation with meat quality grade (r=0.444). Therefore, there are required to manage the breeding through selection of excellent native species for increasing their carcass weight and enhance meat quality.

  11. Effects of Carcass Weight and Back-fat Thickness on Carcass Properties of Korean Native Pigs

    PubMed Central

    2017-01-01

    Our study analyzed the carcass properties of 170 Korean native pigs in relation to carcass weight and back-fat thickness to provide general data for the production and distribution of high quality pig meat. The 70-74 kg group showed highest yield (73.41%). The ≥80 kg group showed the highest thickest back-fat (24.13 mm) (p<0.05). The ≥80 kg group showed the best quality grade (1.00). Back-fat thickness showed significant differences in the weight among groups (p<0.05). The ≥25 mm group showed the highest carcass weight (75.93 kg). The thickest back-fat group (≥25 mm) showed the highest yield (73.03%). There were significant differences in back-fat thickness among groups (p<0.05), and the ≥25 mm group showed the highest thickness back-fat (27.60 mm). We found a strong positive correlation between carcass weight and back-fat thickness (r=0.346) as well as meat quality grade (r=0.739). Back-fat thickness had a relatively strong positive correlation with meat quality grade (r=0.444). Therefore, there are required to manage the breeding through selection of excellent native species for increasing their carcass weight and enhance meat quality. PMID:28747824

  12. Engineering lipid structure for recognition of the liquid ordered membrane phase

    DOE PAGES

    Bordovsky, Stefan S.; Wong, Christopher S.; Bachand, George D.; ...

    2016-08-26

    The selective partitioning of lipid components in phase-separated membranes is essential for domain formation involved in cellular processes. Identifying and tracking the movement of lipids in cellular systems would be improved if we understood how to achieve selective affinity between fluorophore-labeled lipids and membrane assemblies. Furthermore, we investigated the structure and chemistry of membrane lipids to evaluate lipid designs that partition to the liquid ordered (L o) phase. A range of fluorophores at the headgroup position and lengths of PEG spacer between the lipid backbone and fluorophore were examined. On a lipid body with saturated palmityl or palmitoyl tails, wemore » found that although the lipid tails can direct selective partitioning to the L o phase through favorable packing interactions, headgroup hydrophobicity can override the partitioning behavior and direct the lipid to the disordered membrane phase (L d). The PEG spacer can serve as a buffer to mute headgroup–membrane interactions and thus improve L o phase partitioning, but its effect is limited with strongly hydrophobic fluorophore headgroups. We present a series of lipid designs leading to the development of novel fluorescently labeled lipids with selective affinity for the L o phase.« less

  13. Engineering Lipid Structure for Recognition of the Liquid Ordered Membrane Phase.

    PubMed

    Bordovsky, Stefan S; Wong, Christopher S; Bachand, George D; Stachowiak, Jeanne C; Sasaki, Darryl Y

    2016-11-29

    The selective partitioning of lipid components in phase-separated membranes is essential for domain formation involved in cellular processes. Identifying and tracking the movement of lipids in cellular systems would be improved if we understood how to achieve selective affinity between fluorophore-labeled lipids and membrane assemblies. Here, we investigated the structure and chemistry of membrane lipids to evaluate lipid designs that partition to the liquid ordered (L o ) phase. A range of fluorophores at the headgroup position and lengths of PEG spacer between the lipid backbone and fluorophore were examined. On a lipid body with saturated palmityl or palmitoyl tails, we found that although the lipid tails can direct selective partitioning to the L o phase through favorable packing interactions, headgroup hydrophobicity can override the partitioning behavior and direct the lipid to the disordered membrane phase (L d ). The PEG spacer can serve as a buffer to mute headgroup-membrane interactions and thus improve L o phase partitioning, but its effect is limited with strongly hydrophobic fluorophore headgroups. We present a series of lipid designs leading to the development of novel fluorescently labeled lipids with selective affinity for the L o phase.

  14. Patterns of Positive Selection of the Myogenic Regulatory Factor Gene Family in Vertebrates

    PubMed Central

    Zhao, Xiao; Yu, Qi; Huang, Ling; Liu, Qing-Xin

    2014-01-01

    The functional divergence of transcriptional factors is critical in the evolution of transcriptional regulation. However, the mechanism of functional divergence among these factors remains unclear. Here, we performed an evolutionary analysis for positive selection in members of the myogenic regulatory factor (MRF) gene family of vertebrates. We selected 153 complete vertebrate MRF nucleotide sequences from our analyses, which revealed substantial evidence of positive selection. Here, we show that sites under positive selection were more frequently detected and identified from the genes encoding the myogenic differentiation factors (MyoG and Myf6) than the genes encoding myogenic determination factors (Myf5 and MyoD). Additionally, the functional divergence within the myogenic determination factors or differentiation factors was also under positive selection pressure. The positive selection sites were more frequently detected from MyoG and MyoD than Myf6 and Myf5, respectively. Amino acid residues under positive selection were identified mainly in their transcription activation domains and on the surface of protein three-dimensional structures. These data suggest that the functional gain and divergence of myogenic regulatory factors were driven by distinct positive selection of their transcription activation domains, whereas the function of the DNA binding domains was conserved in evolution. Our study evaluated the mechanism of functional divergence of the transcriptional regulation factors within a family, whereby the functions of their transcription activation domains diverged under positive selection during evolution. PMID:24651579

  15. Strong positive cooperativity in binding to the A3T3 repeat by Hoechst 33258 derivatives attaching the quinoline units at the end of a branched linker.

    PubMed

    Koda, Hironori; Brazier, John Alan; Onishi, Ippei; Sasaki, Shigeki

    2015-08-01

    Hoechst 33258 derivatives with additional interacting moieties attached at the ends of branched linkers were synthesized, and their DNA binding properties were investigated with regard to the A3T3 repeat by measuring fluorescence spectra. The binding property of the ligand was investigated by fluorescence titration, and the titration data were analyzed using the McGhee-von Hippel method. Ligand 6Q with the quinolin-6-yloxyacetyl group and Ligand IQ with isoquinolin-6-yloxyacetyl group at the ends of the branched linkers exhibit highly positive cooperativity for the DNA having 5 A3T3 sites with 3 base-insertions between them with sequence selectivity. The strategy developed in this study may be generally applicable for designing ligands for repetitive DNA sequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Discrimination of selected species of pathogenic bacteria using near-infrared Raman spectroscopy and principal components analysis

    NASA Astrophysics Data System (ADS)

    de Siqueira e Oliveira, Fernanda S.; Giana, Hector E.; Silveira, Landulfo, Jr.

    2012-03-01

    It has been proposed a method based on Raman spectroscopy for identification of different microorganisms involved in bacterial urinary tract infections. Spectra were collected from different bacterial colonies (Gram negative: E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, E. cloacae and Gram positive: S. aureus and Enterococcus sp.), grown in culture medium (Agar), using a Raman spectrometer with a fiber Raman probe (830 nm). Colonies were scraped from Agar surface placed in an aluminum foil for Raman measurements. After pre-processing, spectra were submitted to a Principal Component Analysis and Mahalanobis distance (PCA/MD) discrimination algorithm. It has been found that the mean Raman spectra of different bacterial species show similar bands, being the S. aureus well characterized by strong bands related to carotenoids. PCA/MD could discriminate Gram positive bacteria with sensitivity and specificity of 100% and Gram negative bacteria with good sensitivity and high specificity.

  17. Expectations about Memory Change Across the Life Span Are Impacted By Aging Stereotypes

    PubMed Central

    Lineweaver, Tara T.; Berger, Andrea K.; Hertzog, Christopher

    2008-01-01

    This study examined whether expectations about memory change with age vary for different personality types. Four adjectives from each of Hummert’s age-stereotype trait sets were selected to create 11 adjective clusters varying in both valence (positive versus negative) and relevance to memory functioning. Three hundred and seventy three participants in three age groups rated the memory abilities of target adults, defined by the adjective clusters, across the adult life span. Consistent with past studies, participants believed in age-related memory decline. However, participants rated target adults with positive personality traits as having better memory ability and less age-related memory decline than target adults with negative personality traits. This effect was larger when the traits were relevant to memory than when they were not. Finally, older participants were more strongly influenced by both the valence and the relevance of the personality descriptions than younger participants. PMID:19290748

  18. Space Weather Research in the Equatorial Region: A Philosophical Reinforcement

    NASA Astrophysics Data System (ADS)

    Chukwuma, Victor; Odunaike, Rasaki; Laoye, John

    Investigations using radio waves reflected from the ionosphere, at high-and mid-latitudes indicate that ionospheric absorption can strongly increase following geomagnetic storms; which appears to suggest some definite relationship between ionospheric radio wave absorption and geomagnetic storms at these latitudes. However, corresponding earlier studies in the equatorial region did not appear to show any explicit relationship between ionospheric radio wave absorption and geomagnetic storm activity. This position appeared acceptable to the existing scientific paradigm, until in an act of paradigm shift, by a change of storm selection criteria, some more recent space weather investigations in the low latitudes showed that ionospheric radio wave absorption in the equatorial region clearly increases after intense storms. Given that these results in the equatorial region stood against the earlier results, this paper presently attempts to highlight their philosophical underpinning and posit that they constitute a scientific statement.

  19. Body size mediates social and environmental effects on nest building behaviour in a fish with paternal care.

    PubMed

    Lehtonen, Topi K; Lindström, Kai; Wong, Bob B M

    2015-07-01

    Body size, social setting, and the physical environment can all influence reproductive behaviours, but their interactions are not well understood. Here, we investigated how male body size, male-male competition, and water turbidity influence nest-building behaviour in the sand goby (Pomatoschistus minutus), a marine fish with exclusive paternal care. We found that environmental and social factors affected the nest characteristics of small and large males differently. In particular, association between male size and the level of nest elaboration (i.e. the amount of sand piled on top of the nest) was positive only under clear water conditions. Similarly, male size and nest entrance size were positively associated only in the absence of competition. Such interactions may, in turn, help to explain the persistence of variation in reproductive behaviours, which-due to their importance in offspring survival-are otherwise expected to be under strong balancing selection.

  20. Prevalence and pathogens of subclinical mastitis in dairy goats in China.

    PubMed

    Zhao, Yanqing; Liu, Hui; Zhao, Xuanduo; Gao, Yang; Zhang, Miaotao; Chen, Dekun

    2015-02-01

    Subclinical mastitis, a costly disease for the dairy industry, is usually caused by intramammary bacterial infection. The aim of this study was to investigate the prevalence of and pathogens involved in subclinical mastitis in dairy goats in China. A total of 683 dairy goats in the main breeding areas of China were selected, and milk samples were collected. Out of these, 313 (45.82 %) goats were detected distinct or strong positive for subclinical mastitis by using California mastitis test. Among these positive goats, 209 milk samples were used to identify the causing agents by a multiplex PCR assay, and results were listed as follows: coagulase-negative staphylococci (59.52 %), Staphylococcus aureus (15.24 %), Escherichia coli (11.43 %), and Streptococcus spp. (10.95 %). In conclusion, subclinical mastitis is a highly prevalent disease in dairy goats in China, and coagulase-negative staphylococci are the predominant pathogens.

  1. Pattern of parental acceptance of management techniques used in pediatric dentistry.

    PubMed

    Peretz, Benjamin; Kharouba, Johnny; Blumer, Sigalit

    2013-01-01

    To evaluate parents' acceptance of management techniques in Israeli pediatric dental clinics. Ninety parents who accompanied their children to three pediatric dental clinics provided information on selected parameters including their attitudes about management techniques. 68.9% of the parents preferred to stay in the treatment room. The most accepted technique was positive reinforcement (81.1%) followed by tell-show-do (TSD) (76.7%, with younger parents more accepting than older, p = 0.049). The least accepted techniques were restraint (1.1%) and voice control (7.8%, especially by parents with the highest dental anxiety, p = 0.002). Sedation was unacceptable by 15.6% of the parents: those with the lowest dental anxiety agreed to sedation significantly more than those with greater dental anxiety (p = 0.031). Parents preferred more positive approaches and management techniques that involve demonstrations geared for the child's level of understanding. Restraint and voice control were more strongly rejected than sedation.

  2. Aspects regarding the hope for successful reintegration of female detainees.

    PubMed

    Enache, Alexandra; Pasca, Viorel; Luta, Veronica; Ciopec, Flavius; Ursachi, Georgeta; Radu, Daniel; Stratul, Stefan; Zarie, Gabriela; Mutiu, Florentina

    2009-04-01

    We investigated in the female inmate population whether they had and which were the foundations of hope for a better future after liberation. We created and applied a questionnaire structured on four general information chapters regarding health, attitude and spiritual life. In total, 67 questions with 293 items. For this study, we selected 62 items. Hope for better reintegration was layed on family support and (re)imployment. The majority considered that the length of the detention influences the chances for social reintegration. The family perception was clarified and the relationship with the parents and spouse was tightened. The spiritual questions reflected a moderate return to religion. The study proved that the female detainees have a positive perception on the role of education and that the efforts of different educational factors during detention was strongly positive. The development of moral, family, social and spiritual values was beneficial and raised the hopes of social reintegration.

  3. A Two-Step Method to Identify Positive Deviant Physician Organizations of Accountable Care Organizations with Robust Performance Management Systems.

    PubMed

    Pimperl, Alexander F; Rodriguez, Hector P; Schmittdiel, Julie A; Shortell, Stephen M

    2018-06-01

    To identify positive deviant (PD) physician organizations of Accountable Care Organizations (ACOs) with robust performance management systems (PMSYS). Third National Survey of Physician Organizations (NSPO3, n = 1,398). Organizational and external factors from NSPO3 were analyzed. Linear regression estimated the association of internal and contextual factors on PMSYS. Two cutpoints (75th/90th percentiles) identified PDs with the largest residuals and highest PMSYS scores. A total of 65 and 41 PDs were identified using 75th and 90th percentiles cutpoints, respectively. The 90th percentile more strongly differentiated PDs from non-PDs. Having a high proportion of vulnerable patients appears to constrain PMSYS development. Our PD identification method increases the likelihood that PD organizations selected for in-depth inquiry are high-performing organizations that exceed expectations. © Health Research and Educational Trust.

  4. Understanding organizational commitment: A meta-analytic examination of the roles of the five-factor model of personality and culture.

    PubMed

    Choi, Daejeong; Oh, In-Sue; Colbert, Amy E

    2015-09-01

    We examined the relationships between the Five-Factor Model (FFM) of personality traits and three forms of organizational commitment (affective, normative, and continuance commitment) and their variability across individualistic and collectivistic cultures. Meta-analytic results based on 55 independent samples from 50 studies (N = 18,262) revealed that (a) all FFM traits had positive relationships with affective commitment; (b) all FFM traits had positive relationships with normative commitment; and (c) Emotional Stability, Extraversion, and Openness to Experience had negative relationships with continuance commitment. In particular, Agreeableness was found to be the trait most strongly related to both affective and normative commitment. The results also showed that Agreeableness had stronger relationships with affective and normative commitment in collectivistic cultures than in individualistic cultures. We provide theoretical and practical implications of these findings for personality, job attitudes, and employee selection and retention. (c) 2015 APA, all rights reserved).

  5. Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review.

    PubMed

    Claydon, Leica S; Chesterton, Linda S; Barlas, Panos; Sim, Julius

    2011-09-01

    To determine the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) parameter combinations on experimental models in healthy humans. Searches were performed using the electronic databases Ovid MEDLINE, CINAHL, AMED, and Web of Science (from inception to December 2009). Manual searches of journals and reference lists of retrieved trials were also performed. Randomized controlled trials (RCTs) were included in the review if they compared the hypoalgesic effect of TENS relative with placebo and control, using an experimental pain model in healthy human participants. Two reviewers independently selected the trials, assessed their methodologic quality and extracted data. Forty-three RCTs were eligible for inclusion. A best evidence synthesis revealed: Overall "conflicting" (inconsistent findings in multiple RCTs) evidence of TENS efficacy on experimental pain irrespective of TENS parameters used. Overall intense TENS has "moderate" evidence of efficacy (1 high-quality and 2 low-quality trials). Conventional TENS has overall conflicting evidence of efficacy, this is derived from "strong" evidence of efficacy (generally consistent findings in multiple high-quality RCTs) on pressure pain but strong evidence of inefficacy on other pain models. "Limited" evidence (positive findings from 1 RCT) of hypoalgesia exists for some novel parameters. Low-intensity, low-frequency, local TENS has strong evidence of inefficacy. Inappropriate TENS (using "barely perceptible" intensities) has moderate evidence of inefficacy. The level of hypoalgesic efficacy of TENS is clearly dependent on TENS parameter combination selection (defined in terms of intensity, frequency, and stimulation site) and experimental pain model. Future clinical RCTs may consider these TENS dose responses.

  6. CPT1A Missense Mutation Associated With Fatty Acid Metabolism and Reduced Height in Greenlanders.

    PubMed

    Skotte, Line; Koch, Anders; Yakimov, Victor; Zhou, Sirui; Søborg, Bolette; Andersson, Mikael; Michelsen, Sascha W; Navne, Johan E; Mistry, Jacqueline M; Dion, Patrick A; Pedersen, Michael L; Børresen, Malene L; Rouleau, Guy A; Geller, Frank; Melbye, Mads; Feenstra, Bjarke

    2017-06-01

    Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-based sample of 1570 Greenlanders. Using array-based and targeted genotyping, we found that rs80356779, a p.Pro479Leu variant in CPT1A , was strongly associated with markers of n -3 fatty acid metabolism, including degree of unsaturation ( P =1.16×10 - 34 ), levels of polyunsaturated fatty acids, n -3 fatty acids, and docosahexaoenic acid relative to total fatty acid levels ( P =2.35×10 - 15 , P =4.02×10 - 19 , and P =7.92×10 - 27 ). The derived allele (L479) occurred at a frequency of 76.2% in our sample while being absent in most other populations, and we found strong signatures of positive selection at the locus. Furthermore, we found that each copy of L479 reduced height by an average of 2.1 cm ( P =1.04×10 - 9 ). In exome sequencing data from a sister population, the Nunavik Inuit, we found no other likely causal candidate variant than rs80356779. Our study shows that a common CPT1A missense mutation is strongly associated with a range of metabolic phenotypes and reduced height in Greenlanders. These findings are important from a public health perspective and highlight the usefulness of complex trait genetic studies in isolated populations. © 2017 American Heart Association, Inc.

  7. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

    PubMed Central

    van der Putten, Louis JM; Visser, Nicole CM; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc PLM; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon FAG; Pijnenborg, Johanna MA

    2016-01-01

    Background: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. Methods: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. Results: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. Conclusions: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied. PMID:27505134

  8. Strong Selection at MHC in Mexicans since Admixture

    PubMed Central

    Zhou, Quan; Zhao, Liang; Guan, Yongtao

    2016-01-01

    Mexicans are a recent admixture of Amerindians, Europeans, and Africans. We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP, and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the genome, which is the hallmark of recent selection for admixed samples. The estimated selection coefficients are 0.05 and 0.07 for two datasets, which put our finding among the strongest known selections observed in humans, namely, lactase selection in northern Europeans and sickle-cell trait in Africans. Using inaccurate Amerindian training samples was a major concern for the credibility of previously reported selection signals in Latinos. Taking advantage of the flexibility of our statistical model, we devised a model fitting technique that can learn Amerindian ancestral haplotype from the admixed samples, which allows us to infer local ancestries for Mexicans using only European and African training samples. The strong selection signal at the MHC remains without Amerindian training samples. Finally, we note that medical history studies suggest such a strong selection at MHC is plausible in Mexicans. PMID:26863142

  9. Cognitive-Processing Bias in Chinese Student Teachers with Strong and Weak Professional Identity.

    PubMed

    Wang, Xin-Qiang; Zhu, Jun-Cheng; Liu, Lu; Chen, Xiang-Yu

    2017-01-01

    Professional identity plays an important role in career development. Although many studies have examined professional identity, differences in cognitive-processing biases between Chinese student teachers with strong and weak professional identity are poorly understood. The current study adopted Tversky's social-cognitive experimental paradigm to explore cognitive-processing biases in Chinese student teachers with strong and weak professional identity. Experiment 1 showed that participants with strong professional identity exhibited stronger positive-coding bias toward positive profession-related life events, relative to that observed in those with weak professional identity. Experiment 2 showed that participants with strong professional identity exhibited greater recognition bias for previously read items, relative to that observed in those with weak professional identity. Overall, the results suggested that participants with strong professional identity exhibited greater positive cognitive-processing bias relative to that observed in those with weak professional identity.

  10. Cognitive-Processing Bias in Chinese Student Teachers with Strong and Weak Professional Identity

    PubMed Central

    Wang, Xin-qiang; Zhu, Jun-cheng; Liu, Lu; Chen, Xiang-yu

    2017-01-01

    Professional identity plays an important role in career development. Although many studies have examined professional identity, differences in cognitive-processing biases between Chinese student teachers with strong and weak professional identity are poorly understood. The current study adopted Tversky’s social-cognitive experimental paradigm to explore cognitive-processing biases in Chinese student teachers with strong and weak professional identity. Experiment 1 showed that participants with strong professional identity exhibited stronger positive-coding bias toward positive profession-related life events, relative to that observed in those with weak professional identity. Experiment 2 showed that participants with strong professional identity exhibited greater recognition bias for previously read items, relative to that observed in those with weak professional identity. Overall, the results suggested that participants with strong professional identity exhibited greater positive cognitive-processing bias relative to that observed in those with weak professional identity. PMID:28555123

  11. Asymmetric band gaps in a Rashba film system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carbone, C.; Moras, P.; Sheverdyaeva, P. M.

    The joint effect of exchange and Rashba spin-orbit interactions is examined on the surface and quantum well states of Ag 2 Bi -terminated Ag films grown on ferromagnetic Fe(110). The system displays a particular combination of time-reversal and translational symmetry breaking that strongly influences its electronic structure. Angle-resolved photoemission reveals asymmetric band-gap openings, due to spin-selective hybridization between Rashba-split surface states and exchange-split quantum well states. This results in an unequal number of states along positive and negative reciprocal space directions. We suggest that the peculiar asymmetry of the discovered electronic structure can have significant influence on spin-polarized transport properties.

  12. A review of selected candidate endophenotypes for depression.

    PubMed

    Goldstein, Brandon L; Klein, Daniel N

    2014-07-01

    Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Synergistic Heterobimetallic Manifold for Expedient Manganese(I)-Catalyzed C-H Cyanation.

    PubMed

    Liu, Weiping; Richter, Sven C; Mei, Ruhuai; Feldt, Milica; Ackermann, Lutz

    2016-12-12

    The manganese-catalyzed cyanation of inert C-H bonds was achieved within a heterobimetallic catalysis regime. The manganese(I) catalysis proved widely applicable and enabled C-H cyanations on indoles, pyrroles and thiophenes by facile C-H manganesation. The robustness of the manganese catalyst set the stage for the racemization-free C-H cyanation of amino acids with excellent levels of positional and chemo selectivity by the new cyanating agent NCFS. Experimental and computational mechanistic studies provided strong support for a synergistic heterobimetallic activation mode, facilitating the key C-C formation. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Health, Information, and Migration: Geographic Mobility of Union Army Veterans, 1860–1880

    PubMed Central

    Lee, Chulhee

    2009-01-01

    This article explores how injuries, sickness, and the geographic mobility of Union Army veterans while in service affected their postservice migrations. Wartime wounds and illnesses significantly diminished the geographic mobility of veterans after the war. Geographic moves while carrying out military missions had strong positive effects on their postservice geographic mobility. Geographic moves while in service also influenced the choice of destination among the migrants. I discuss some implications of the results for the elements of self-selection in migration, the roles of different types of information in migration decisions, and the overall impact of the Civil War on geographic mobility. PMID:20234796

  15. Livestock improvement: art, science, or industry?

    PubMed

    Harris, D L

    1998-09-01

    The shift in perspectives about livestock improvement over a 70-yr period is reviewed. The view changes from livestock improvement as an art, through its becoming a science, to its application as a technology in industry. The use of scientific tools in corporate settings for poultry, dairy, and swine breeding usually involves a strong focus on the economics of production, and this focus determines that selection indexes should be used. Such focus has seemed to not have been present in breeding for the extensively managed species and livestock classes but seems needed in order to provide a basis for organization and direction of positive contributions of the breeding segment to the production segment.

  16. The genetic basis of adaptive pigmentation variation in Drosophila melanogaster

    PubMed Central

    Pool, John E.; Aquadro, Charles F.

    2009-01-01

    In a broad survey of Drosophila melanogaster population samples, levels of abdominal pigmentation were found to be highly variable and geographically differentiated. A strong positive correlation was found between dark pigmentation and high altitude, suggesting adaptation to specific environments. DNA sequence polymorphism at the candidate gene ebony revealed a clear association with the pigmentation of homozygous third chromosome lines. The darkest lines sequenced had nearly identical haplotypes spanning 14.5 kilobases upstream of the protein-coding exons of ebony. Thus, natural selection may have elevated the frequency of an allele that confers dark abdominal pigmentation by influencing the regulation of ebony. PMID:17614900

  17. Strong selection on mandible and nest features in a carpenter bee that nests in two sympatric host plants

    PubMed Central

    Flores-Prado, Luis; Pinto, Carlos F; Rojas, Alejandra; Fontúrbel, Francisco E

    2014-01-01

    Host plants are used by herbivorous insects as feeding or nesting resources. In wood-boring insects, host plants features may impose selective forces leading to phenotypic differentiation on traits related to nest construction. Carpenter bees build their nests in dead stems or dry twigs of shrubs and trees; thus, mandibles are essential for the nesting process, and the nest is required for egg laying and offspring survival. We explored the shape and intensity of natural selection on phenotypic variation on three size measures of the bees (intertegular width, wing length, and mandible area) and two nest architecture measures (tunnel length and diameter) on bees using the native species Chusquea quila (Poaceae), and the alloctonous species Rubus ulmifolius (Rosaceae), in central Chile. Our results showed significant and positive linear selection gradients for tunnel length on both hosts, indicating that bees building long nests have more offspring. Bees with broader mandibles show greater fitness on C. quila but not on R. ulmifolius. Considering that C. quila represents a selective force on mandible area, we hypothesized a high adaptive value of this trait, resulting in higher fitness values when nesting on this host, despite its wood is denser and hence more difficult to be bored. PMID:24963379

  18. Strong selection on mandible and nest features in a carpenter bee that nests in two sympatric host plants.

    PubMed

    Flores-Prado, Luis; Pinto, Carlos F; Rojas, Alejandra; Fontúrbel, Francisco E

    2014-05-01

    Host plants are used by herbivorous insects as feeding or nesting resources. In wood-boring insects, host plants features may impose selective forces leading to phenotypic differentiation on traits related to nest construction. Carpenter bees build their nests in dead stems or dry twigs of shrubs and trees; thus, mandibles are essential for the nesting process, and the nest is required for egg laying and offspring survival. We explored the shape and intensity of natural selection on phenotypic variation on three size measures of the bees (intertegular width, wing length, and mandible area) and two nest architecture measures (tunnel length and diameter) on bees using the native species Chusquea quila (Poaceae), and the alloctonous species Rubus ulmifolius (Rosaceae), in central Chile. Our results showed significant and positive linear selection gradients for tunnel length on both hosts, indicating that bees building long nests have more offspring. Bees with broader mandibles show greater fitness on C. quila but not on R. ulmifolius. Considering that C. quila represents a selective force on mandible area, we hypothesized a high adaptive value of this trait, resulting in higher fitness values when nesting on this host, despite its wood is denser and hence more difficult to be bored.

  19. Influenza virus drug resistance: a time-sampled population genetics perspective.

    PubMed

    Foll, Matthieu; Poh, Yu-Ping; Renzette, Nicholas; Ferrer-Admetlla, Anna; Bank, Claudia; Shim, Hyunjin; Malaspinas, Anna-Sapfo; Ewing, Gregory; Liu, Ping; Wegmann, Daniel; Caffrey, Daniel R; Zeldovich, Konstantin B; Bolon, Daniel N; Wang, Jennifer P; Kowalik, Timothy F; Schiffer, Celia A; Finberg, Robert W; Jensen, Jeffrey D

    2014-02-01

    The challenge of distinguishing genetic drift from selection remains a central focus of population genetics. Time-sampled data may provide a powerful tool for distinguishing these processes, and we here propose approximate Bayesian, maximum likelihood, and analytical methods for the inference of demography and selection from time course data. Utilizing these novel statistical and computational tools, we evaluate whole-genome datasets of an influenza A H1N1 strain in the presence and absence of oseltamivir (an inhibitor of neuraminidase) collected at thirteen time points. Results reveal a striking consistency amongst the three estimation procedures developed, showing strongly increased selection pressure in the presence of drug treatment. Importantly, these approaches re-identify the known oseltamivir resistance site, successfully validating the approaches used. Enticingly, a number of previously unknown variants have also been identified as being positively selected. Results are interpreted in the light of Fisher's Geometric Model, allowing for a quantification of the increased distance to optimum exerted by the presence of drug, and theoretical predictions regarding the distribution of beneficial fitness effects of contending mutations are empirically tested. Further, given the fit to expectations of the Geometric Model, results suggest the ability to predict certain aspects of viral evolution in response to changing host environments and novel selective pressures.

  20. Substitutions in the Glycogenin-1 Gene Are Associated with the Evolution of Endothermy in Sharks and Tunas.

    PubMed

    Ciezarek, Adam G; Dunning, Luke T; Jones, Catherine S; Noble, Leslie R; Humble, Emily; Stefanni, Sergio S; Savolainen, Vincent

    2016-10-05

    Despite 400-450 million years of independent evolution, a strong phenotypic convergence has occurred between two groups of fish: tunas and lamnid sharks. This convergence is characterized by centralization of red muscle, a distinctive swimming style (stiffened body powered through tail movements) and elevated body temperature (endothermy). Furthermore, both groups demonstrate elevated white muscle metabolic capacities. All these traits are unusual in fish and more likely evolved to support their fast-swimming, pelagic, predatory behavior. Here, we tested the hypothesis that their convergent evolution was driven by selection on a set of metabolic genes. We sequenced white muscle transcriptomes of six tuna, one mackerel, and three shark species, and supplemented this data set with previously published RNA-seq data. Using 26 species in total (including 7,032 tuna genes plus 1,719 shark genes), we constructed phylogenetic trees and carried out maximum-likelihood analyses of gene selection. We inferred several genes relating to metabolism to be under selection. We also found that the same one gene, glycogenin-1, evolved under positive selection independently in tunas and lamnid sharks, providing evidence of convergent selective pressures at gene level possibly underlying shared physiology. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Turbulent Boundary Layers in Oscillating Flows. Part 1: an Experimental and Computational Study

    NASA Technical Reports Server (NTRS)

    Cook, W. J.

    1986-01-01

    An experimental-computational study of the behavior of turbulent boundary layers for oscillating air flows over a plane surface with a small favorable mean pressure gradient is described. Experimental studies were conducted for boundary layers generated on the test section wall of a facility that produces a flow with a mean free stream velocity and a superposed nearly-pure sinusoidal component over a wide range of frequency. Flow at a nominal mean free stream velocity of 50 m/s were studied at atmospheric pressure and temperature at selected axial positions over a 2 m test length for frequencies ranging from 4 to 29 Hz. Quantitative experimental results are presented for unsteady velocity profiles and longitudinal turbulence levels obtained from hot wire anemometer measurements at three axial positions. Mean velocity profiles for oscillating flows were found to exhibit only small deviations from corresponding steady flow profiles, while amplitudes and phase relationships exhibited a strong dependence on axial position and frequency. Since sinusoidal flows could be generated over a wide range of frequency, studies at fixed values of reduced frequency at different axial positions were studied. Results show that there is some utility in the use of reduced frequency to correlate unsteady velocity results. The turbulence level u' sub rms was observed to vary essentially sinusoidally around values close to those measured in steady flow. However, the amplitude of oscillation and phase relations for turbulence level were found to be strongly frequency dependent. Numerical predictions were obtained using an unsteady boundary layer computational code and the Cebeci-Smith and Glushko turbulence models. Predicted quantities related to unsteady velocity profiles exhibit fair agreement with experiment when the Cebeci-Smith turbulence model is used.

  2. Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes.

    PubMed

    Karn, Robert C; Laukaitis, Christina M

    2014-08-01

    In the present article, we summarize two aspects of our work on mouse ABP (androgen-binding protein): (i) the sexual selection function producing incipient reinforcement on the European house mouse hybrid zone, and (ii) the mechanism behind the dramatic expansion of the Abp gene region in the mouse genome. Selection unifies these two components, although the ways in which selection has acted differ. At the functional level, strong positive selection has acted on key sites on the surface of one face of the ABP dimer, possibly to influence binding to a receptor. A different kind of selection has apparently driven the recent and rapid expansion of the gene region, probably by increasing the amount of Abp transcript, in one or both of two ways. We have shown previously that groups of Abp genes behave as LCRs (low-copy repeats), duplicating as relatively large blocks of genes by NAHR (non-allelic homologous recombination). The second type of selection involves the close link between the accumulation of L1 elements and the expansion of the Abp gene family by NAHR. It is probably predicated on an initial selection for increased transcription of existing Abp genes and/or an increase in Abp gene number providing more transcriptional sites. Either or both could increase initial transcript production, a quantitative change similar to increasing the volume of a radio transmission. In closing, we also provide a note on Abp gene nomenclature.

  3. STRONG SOLAR WIND DYNAMIC PRESSURE PULSES: INTERPLANETARY SOURCES AND THEIR IMPACTS ON GEOSYNCHRONOUS MAGNETIC FIELDS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zuo, Pingbing; Feng, Xueshang; Wang, Yi

    In this investigation, we first present a statistical result of the interplanetary sources of very strong solar wind dynamic pressure pulses (DPPs) detected by WIND during solar cycle 23. It is found that the vast majority of strong DPPs reside within solar wind disturbances. Although the variabilities of geosynchronous magnetic fields (GMFs) due to the impact of positive DPPs have been well established, there appears to be no systematic investigations on the response of GMFs to negative DPPs. Here, we study both the decompression effects of very strong negative DPPs and the compression from strong positive DPPs on GMFs atmore » different magnetic local time sectors. In response to the decompression of strong negative DPPs, GMFs on the dayside near dawn and near dusk on the nightside, are generally depressed. But near the midnight region, the responses of GMF are very diverse, being either positive or negative. For part of the events when GOES is located at the midnight sector, the GMF is found to abnormally increase as the result of magnetospheric decompression caused by negative DPPs. It is known that under certain conditions magnetic depression of nightside GMFs can be caused by the impact of positive DPPs. Here, we find that a stronger pressure enhancement may have a higher probability of producing the exceptional depression of GMF at the midnight region. Statistically, both the decompression effect of strong negative DPPs and the compression effect of strong positive DPPs depend on the magnetic local time, which are stronger at the noon sector.« less

  4. Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.

    PubMed

    Fetterman, Christina D; Rannala, Bruce; Walter, Michael A

    2008-09-24

    Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. Consideration of selection pressures observed in conjunction with known functional information allowed prediction of residue function and refinement of domain boundaries. Identification of residues that differentiate orthologs and paralogs provided insight into the development and functional consequences of paralogs and forkhead subfamily composition differences among species. Overall we found that after gene duplication of forkhead family members, rapid differentiation and subsequent fixation of amino acid changes through negative selection has occurred.

  5. Parallel evolution or purifying selection, not introgression, explain similarity in the pyrethroid detoxification linked GSTE4 of Anopheles gambiae and An. arabiensis

    PubMed Central

    Wilding, C.S.; Weetman, D.; Rippon, E.J.; Steen, K.; Mawejje, H.D.; Barsukov, I.; Donnelly, M.J.

    2014-01-01

    Insecticide resistance is a major impediment to the control of vectors and pests of public health importance and is a strongly selected trait capable of rapid spread, sometimes even between closely-related species. Elucidating the mechanisms generating insecticide resistance in mosquito vectors of disease, and understanding the spread of resistance within and between populations and species are vital for the development of robust resistance management strategies. Here we studied the mechanisms of resistance in two sympatric members of the Anopheles gambiae species complex – the major vector of malaria in sub-Saharan Africa – in order to understand how resistance has developed and spread in eastern Uganda, a region with some of the highest levels of malaria. In eastern Uganda, where the mosquitoes Anopheles arabiensis and An. gambiae can be found sympatrically, low levels of hybrids (0.4%) occur, offering a route for introgression of adaptively important variants between species. In independent microarray studies of insecticide resistance, Gste4, an insect-specific glutathione S-transferase, was among the most significantly up-regulated genes in both species. To test the hypothesis of interspecific introgression, we sequenced 2.3kbp encompassing Gste4. Whilst this detailed sequencing ruled out introgression, we detected strong positive selection acting on Gste4. However, these sequences, followed by haplotype-specific qPCR, showed that the apparent up-regulation in An. arabiensis is a result of allelic variation across the microarray probe binding sites which artefactually elevates the gene expression signal. Thus, face-value acceptance of microarray data can be misleading and it is advisable to conduct a more detailed investigation of the causes and nature of such signal. The identification of positive selection acting on this locus led us to functionally express and characterise allelic variants of GSTE4. Although the in vitro data do not support a direct role for GSTE4 in metabolism, they do support a role for this enzyme in insecticide sequestration. Thus, the demonstration of a role for an up-regulated gene in metabolic resistance to insecticides should not be limited to simply whether it can metabolise insecticide; such a strict criterion would argue against the involvement of GSTE4 despite the weight of evidence to the contrary. PMID:25213601

  6. What is the effect of physical activity on the knee joint? A systematic review.

    PubMed

    Urquhart, Donna M; Tobing, Jephtah F L; Hanna, Fahad S; Berry, Patricia; Wluka, Anita E; Ding, Changhai; Cicuttini, Flavia M

    2011-03-01

    Although several studies have examined the relationship between physical activity and knee osteoarthritis, the effect of physical activity on knee joint health is unclear. The aim of this systematic review was to examine the relationships between physical activity and individual joint structures at the knee. Computer-aided searches were conducted up until November 2008, and the reference lists of key articles were examined. The methodological quality of selected studies was assessed based on established criteria, and a best-evidence synthesis was used to summarize the results. We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects. This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health.

  7. Resonant absorption and amplification of circularly-polarized waves in inhomogeneous chiral media.

    PubMed

    Kim, Seulong; Kim, Kihong

    2016-01-25

    It has been found that in the media where the dielectric permittivity ε or the magnetic permeability μ is near zero and in transition metamaterials where ε or μ changes from positive to negative values, there occur a strong absorption or amplification of the electromagnetic wave energy in the presence of an infinitesimally small damping or gain and a strong enhancement of the electromagnetic fields. We attribute these phenomena to the mode conversion of transverse electromagnetic waves into longitudinal plasma oscillations and its inverse process. In this paper, we study analogous phenomena occurring in chiral media theoretically using the invariant imbedding method. In uniform isotropic chiral media, right-circularly-polarized and left-circularly-polarized waves are the eigen-modes of propagation with different effective refractive indices n(+) and n(-), whereas in the chiral media with a nonuniform impedance variation, they are no longer the eigenmodes and are coupled to each other. We find that both in uniform chiral slabs where either n(+) or n(-) is near zero and in chiral transition metamaterials where n(+) or n(-) changes from positive to negative values, a strong absorption or amplification of circularly-polarized waves occurs in the presence of an infinitesimally small damping or gain. We present detailed calculations of the mode conversion coefficient, which measures the fraction of the electromagnetic wave energy absorbed into the medium, for various configurations of ε and μ with an emphasis on the influence of a nonuniform impedance. We propose possible applications of these phenomena to linear and nonlinear optical devices that react selectively to the helicity of the circular polarization.

  8. Selective mutism.

    PubMed

    Hua, Alexandra; Major, Nili

    2016-02-01

    Selective mutism is a disorder in which an individual fails to speak in certain social situations though speaks normally in other settings. Most commonly, this disorder initially manifests when children fail to speak in school. Selective mutism results in significant social and academic impairment in those affected by it. This review will summarize the current understanding of selective mutism with regard to diagnosis, epidemiology, cause, prognosis, and treatment. Studies over the past 20 years have consistently demonstrated a strong relationship between selective mutism and anxiety, most notably social phobia. These findings have led to the recent reclassification of selective mutism as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. In addition to anxiety, several other factors have been implicated in the development of selective mutism, including communication delays and immigration/bilingualism, adding to the complexity of the disorder. In the past few years, several randomized studies have supported the efficacy of psychosocial interventions based on a graduated exposure to situations requiring verbal communication. Less data are available regarding the use of pharmacologic treatment, though there are some studies that suggest a potential benefit. Selective mutism is a disorder that typically emerges in early childhood and is currently conceptualized as an anxiety disorder. The development of selective mutism appears to result from the interplay of a variety of genetic, temperamental, environmental, and developmental factors. Although little has been published about selective mutism in the general pediatric literature, pediatric clinicians are in a position to play an important role in the early diagnosis and treatment of this debilitating condition.

  9. MHC II-β chain gene expression studies define the regional organization of the thymus in the developing bony fish Dicentrarchus labrax (L.).

    PubMed

    Picchietti, S; Abelli, L; Guerra, L; Randelli, E; Proietti Serafini, F; Belardinelli, M C; Buonocore, F; Bernini, C; Fausto, A M; Scapigliati, G

    2015-02-01

    MHC II-β chain gene transcripts were quantified by real-time PCR and localised by in situ hybridization in the developing thymus of the teleost Dicentrarchus labrax, regarding the specialization of the thymic compartments. MHC II-β expression significantly rose when the first lymphoid colonization of the thymus occurred, thereafter increased further when the organ progressively developed cortex and medulla regions. The evolving patterns of MHC II-β expression provided anatomical insights into some mechanisms of thymocyte selection. Among the stromal cells transcribing MHC II-β, scattered cortical epithelial cells appeared likely involved in the positive selection, while those abundant in the cortico-medullary border and medulla in the negative selection. These latter most represent dendritic cells, based on typical localization and phenotype. These findings provide further proofs that efficient mechanisms leading to maturation of naïve T cells are operative in teleosts, strongly reminiscent of the models conserved in more evolved gnathostomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Succinic acid functionalized silver nanoparticles (Suc-Ag NPs) for colorimetric sensing of melamine

    NASA Astrophysics Data System (ADS)

    Rajar, Kausar; Sirajuddin; Balouch, Aamna; Bhanger, M. I.; Shah, Muhammad Tariq; Shaikh, Tayyaba; Siddiqui, Samia

    2018-03-01

    In this study, a quantitative colorimetric sensing strategy is developed for the rapid, sensitive and selective determination of melamine. The sensing system relies on the application of succinic acid as a selective recognition probe functionalized over Ag NPs. The synthesized Ag NPs were modified with cysteamine to induce positively charged atmosphere which allowed easy and favorable functionalization of succinic acid. The di-carboxyl nature of succinic acid enabled its binding to both cysteamine and melamine. The strong and favorable linkage between succinic acids carbonyl and amine moieties of melamine triggered aggregation of silver NPs producing a significant shift in the measured absorption excitation. This change in the excitation along with the colorimetric response was found linearly proportional to the melamine concentration in the range of 0.1-1.2 μM. The developed sensor system is simple and unlike electrostatic attraction based sensor system utilize selective linkage for the recognition of melamine. In addition to this, the developed optical probe can efficiently be used for the determination of melamine in milk samples.

  11. Discovery of Potent and Selective Dipeptidyl Peptidase IV Inhibitors Derived from [beta]-Aminoamides Bearing Subsituted Triazolopiperazines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Dooseop; Kowalchick, Jennifer E.; Brockunier, Linda L.

    2008-06-30

    A series of {beta}-aminoamides bearing triazolopiperazines have been discovered as potent, selective, and orally active dipeptidyl peptidase IV (DPP-4) inhibitors by extensive structure-activity relationship (SAR) studies around the triazolopiperazine moiety. Among these, compound 34b with excellent in vitro potency (IC{sub 50} = 4.3 nM) against DPP-4, high selectivity over other enzymes, and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in lean mice. On the basis of these properties, compound 34b has been profiled in detail. Further refinement of the triazolopiperazines resulted in the discovery of a series of extremely potent compounds withmore » subnanomolar activity against DPP-4 (42b-49b), that is, 4-fluorobenzyl-substituted compound 46b, which is notable for its superior potency (IC{sub 50} = 0.18 nM). X-ray crystal structure determination of compounds 34b and 46b in complex with DPP-4 enzyme revealed that (R)-stereochemistry at the 8-position of triazolopiperazines is strongly preferred over (S) with respect to DPP-4 inhibition.« less

  12. Evaluation of two main RNA-seq approaches for gene quantification in clinical RNA sequencing: polyA+ selection versus rRNA depletion.

    PubMed

    Zhao, Shanrong; Zhang, Ying; Gamini, Ramya; Zhang, Baohong; von Schack, David

    2018-03-19

    To allow efficient transcript/gene detection, highly abundant ribosomal RNAs (rRNA) are generally removed from total RNA either by positive polyA+ selection or by rRNA depletion (negative selection) before sequencing. Comparisons between the two methods have been carried out by various groups, but the assessments have relied largely on non-clinical samples. In this study, we evaluated these two RNA sequencing approaches using human blood and colon tissue samples. Our analyses showed that rRNA depletion captured more unique transcriptome features, whereas polyA+ selection outperformed rRNA depletion with higher exonic coverage and better accuracy of gene quantification. For blood- and colon-derived RNAs, we found that 220% and 50% more reads, respectively, would have to be sequenced to achieve the same level of exonic coverage in the rRNA depletion method compared with the polyA+ selection method. Therefore, in most cases we strongly recommend polyA+ selection over rRNA depletion for gene quantification in clinical RNA sequencing. Our evaluation revealed that a small number of lncRNAs and small RNAs made up a large fraction of the reads in the rRNA depletion RNA sequencing data. Thus, we recommend that these RNAs are specifically depleted to improve the sequencing depth of the remaining RNAs.

  13. Resolving the conundrum of inbreeding depression but no inbreeding avoidance: Estimating sex‐specific selection on inbreeding by song sparrows (Melospiza melodia)

    PubMed Central

    Reid, Jane M.; Arcese, Peter; Bocedi, Greta; Duthie, A. Bradley; Wolak, Matthew E.; Keller, Lukas F.

    2015-01-01

    Inbreeding avoidance among interacting females and males is not always observed despite inbreeding depression in offspring fitness, creating an apparent “inbreeding paradox.” This paradox could be resolved if selection against inbreeding was in fact weak, despite inbreeding depression. However, the net magnitude and direction of selection on the degree to which females and males inbreed by pairing with relatives has not been explicitly estimated. We used long‐term pedigree data to estimate phenotypic selection gradients on the degree of inbreeding that female and male song sparrows (Melospiza melodia) expressed by forming socially persistent breeding pairs with relatives. Fitness was measured as the total numbers of offspring and grand offspring contributed to the population, and as corresponding expected numbers of identical‐by‐descent allele copies, thereby accounting for variation in offspring survival, reproduction, and relatedness associated with variation in parental inbreeding. Estimated selection gradients on the degree to which individuals paired with relatives were weakly positive in females, but negative in males that formed at least one socially persistent pairing. However, males that paired had higher mean fitness than males that remained socially unpaired. These analyses suggest that net selection against inbreeding may be weak in both sexes despite strong inbreeding depression, thereby resolving the “inbreeding paradox.” PMID:26420476

  14. A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock

    PubMed Central

    Kadri, Naveen Kumar; Sahana, Goutam; Charlier, Carole; Iso-Touru, Terhi; Guldbrandtsen, Bernt; Karim, Latifa; Nielsen, Ulrik Sander; Panitz, Frank; Aamand, Gert Pedersen; Schulman, Nina; Georges, Michel; Vilkki, Johanna; Lund, Mogens Sandø; Druet, Tom

    2014-01-01

    In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated. PMID:24391517

  15. No evidence for positive selection at two potential targets for malaria transmission-blocking vaccines in Anopheles gambiae s.s.

    PubMed

    Crawford, Jacob E; Rottschaefer, Susan M; Coulibaly, Boubacar; Sacko, Madjou; Niaré, Oumou; Riehle, Michelle M; Traore, Sékou F; Vernick, Kenneth D; Lazzaro, Brian P

    2013-06-01

    Human malaria causes nearly a million deaths in sub-Saharan Africa each year. The evolution of drug-resistance in the parasite and insecticide resistance in the mosquito vector has complicated control measures and made the need for new control strategies more urgent. Anopheles gambiae s.s. is one of the primary vectors of human malaria in Africa, and parasite-transmission-blocking vaccines targeting Anopheles proteins have been proposed as a possible strategy to control the spread of the disease. However, the success of these hypothetical technologies would depend on the successful ability to broadly target mosquito populations that may be genetically heterogeneous. Understanding the evolutionary pressures shaping genetic variation among candidate target molecules offers a first step towards evaluating the prospects of successfully deploying such technologies. We studied the population genetics of genes encoding two candidate target proteins, the salivary gland protein saglin and the basal lamina structural protein laminin, in wild populations of the M and S molecular forms of A. gambiae in Mali. Through analysis of intraspecific genetic variation and interspecific comparisons, we found no evidence of positive natural selection at the genes encoding these proteins. On the contrary, we found evidence for particularly strong purifying selection at the laminin gene. These results provide insight into the patterns of genetic diversity of saglin and laminin, and we discuss these findings in relation to the potential development of these molecules as vaccine targets. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Trends of the Major Porin Gene (ompF) Evolution: Insight from the Genus Yersinia

    PubMed Central

    Stenkova, Anna M.; Isaeva, Marina P.; Shubin, Felix N.; Rasskazov, Valeri A.; Rakin, Alexander V.

    2011-01-01

    OmpF is one of the major general porins of Enterobacteriaceae that belongs to the first line of bacterial defense and interactions with the biotic as well as abiotic environments. Porins are surface exposed and their structures strongly reflect the history of multiple interactions with the environmental challenges. Unfortunately, little is known on diversity of porin genes of Enterobacteriaceae and the genus Yersinia especially. We analyzed the sequences of the ompF gene from 73 Yersinia strains covering 14 known species. The phylogenetic analysis placed most of the Yersinia strains in the same line assigned by 16S rDNA-gyrB tree. Very high congruence in the tree topologies was observed for Y. enterocolitica, Y. kristensenii, Y. ruckeri, indicating that intragenic recombination in these species had no effect on the ompF gene. A significant level of intra- and interspecies recombination was found for Y. aleksiciae, Y. intermedia and Y. mollaretii. Our analysis shows that the ompF gene of Yersinia has evolved with nonrandom mutational rate under purifying selection. However, several surface loops in the OmpF porin contain positively selected sites, which very likely reflect adaptive diversification Yersinia to their ecological niches. To our knowledge, this is a first investigation of diversity of the porin gene covering the whole genus of the family Enterobacteriaceae. This study demonstrates that recombination and positive selection both contribute to evolution of ompF, but the relative contribution of these evolutionary forces are different among Yersinia species. PMID:21655186

  17. Correlated responses for litter traits to six generations of selection for ovulation rate or prenatal survival in French Large White pigs.

    PubMed

    Rosendo, A; Druet, T; Gogué, J; Canario, L; Bidanel, J P

    2007-07-01

    Effects of selection for reproductive traits were estimated using data from 3 pig lines derived from the same Large White population base. Two lines were selected for 6 generations on high ovulation rate at puberty (OR line) or high prenatal survival corrected for ovulation rate in the first 2 parities (PS line). The third line was an unselected control line. Genetic parameters for age and BW at puberty (AP and WP); number of piglets born alive, weaned, and nurtured (NBA, NW, and NN, respectively); proportions of stillbirth (PSB) and survival from birth to weaning (PSW); litter and average piglet BW at birth (LWB and AWB), at 21 d (LW21 and AW21), and at weaning (LWW and AWW) were estimated using REML methodology. Heritability estimates were 0.38 +/- 0.03, 0.46 +/- 0.03, 0.16 +/- 0.01, 0.08 +/- 0.01, 0.09 +/- 0.01, 0.04 +/- 0.01, 0.04 +/- 0.02, 0.19 +/- 0.02, 0.10 +/- 0.02, 0.10 +/- 0.02, 0.36 +/- 0.02, 0.27 +/- 0.01, and 0.24 +/- 0.01 for AP, WP, NBA, PSB, NW, NN, PSW, LWB, LW21, LWW, AWB, AW21, and AWW, respectively. The measures of litter size showed strong genetic correlations (r(a) >/= 0.95) and had antagonistic relations with PSB (r(a) = -0.59 to -0.75) and average piglet BW (r(a) = -0.19 to -0.46). They also had strong positive genetic correlations with prenatal survival (r(a) = 0.67 to 0.78) and moderate ones with ovulation rate (r(a) = 0.36 to 0.42). Correlations of litter size with PSW were negative at birth but positive at weaning. The OR and PS lines were negatively related to PSW and average piglet BW. Puberty traits had positive genetic correlations with OR and negative ones with PS. Genetic trends were estimated by computing differences between OR or PS and control lines at each generation using least squares and mixed model methodologies. Average genetic trends were computed by regressing line differences on generation number. Significant (P < 0.05) average genetic trends were obtained in OR and PS lines for AP (respectively, 2.1 +/- 0.9 and 3.2 +/- 1.0 d/generation) and WP (respectively, 2.0 +/- 0.5 and 1.8 +/- 0.5 d/generation) and in the PS line for NBA (0.22 +/- 0.10 piglet/generation). Tendencies (P < 0.10) were also observed for LWB (0.21 +/- 0.12 kg/generation) and AWW (-0.25 +/- 0.14 kg/generation) in the PS line. Selection on components of litter size can be used to improve litter size at birth, but result in undesirable trends for preweaning survival.

  18. Bayesian Variable Selection for Hierarchical Gene-Environment and Gene-Gene Interactions

    PubMed Central

    Liu, Changlu; Ma, Jianzhong; Amos, Christopher I.

    2014-01-01

    We propose a Bayesian hierarchical mixture model framework that allows us to investigate the genetic and environmental effects, gene by gene interactions and gene by environment interactions in the same model. Our approach incorporates the natural hierarchical structure between the main effects and interaction effects into a mixture model, such that our methods tend to remove the irrelevant interaction effects more effectively, resulting in more robust and parsimonious models. We consider both strong and weak hierarchical models. For a strong hierarchical model, both of the main effects between interacting factors must be present for the interactions to be considered in the model development, while for a weak hierarchical model, only one of the two main effects is required to be present for the interaction to be evaluated. Our simulation results show that the proposed strong and weak hierarchical mixture models work well in controlling false positive rates and provide a powerful approach for identifying the predisposing effects and interactions in gene-environment interaction studies, in comparison with the naive model that does not impose this hierarchical constraint in most of the scenarios simulated. We illustrated our approach using data for lung cancer and cutaneous melanoma. PMID:25154630

  19. GABAergic Neurons of the Central Amygdala Promote Cataplexy

    PubMed Central

    Agostinelli, Lindsay J.; Lowell, Bradford B.

    2017-01-01

    Narcolepsy is characterized by chronic sleepiness and cataplexy—sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine-N-oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy. SIGNIFICANCE STATEMENT Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control. PMID:28235898

  20. Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution.

    PubMed

    Oz, Tugce; Guvenek, Aysegul; Yildiz, Sadik; Karaboga, Enes; Tamer, Yusuf Talha; Mumcuyan, Nirva; Ozan, Vedat Burak; Senturk, Gizem Hazal; Cokol, Murat; Yeh, Pamela; Toprak, Erdal

    2014-09-01

    Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Feasibility and validity of the structured attention module among economically disadvantaged preschool-age children.

    PubMed

    Bush, Hillary H; Eisenhower, Abbey; Briggs-Gowan, Margaret; Carter, Alice S

    2015-01-01

    Rooted in the theory of attention put forth by Mirsky, Anthony, Duncan, Ahearn, and Kellam (1991), the Structured Attention Module (SAM) is a developmentally sensitive, computer-based performance task designed specifically to assess sustained selective attention among 3- to 6-year-old children. The current study addressed the feasibility and validity of the SAM among 64 economically disadvantaged preschool-age children (mean age = 58 months; 55% female); a population known to be at risk for attention problems and adverse math performance outcomes. Feasibility was demonstrated by high completion rates and strong associations between SAM performance and age. Principal Factor Analysis with rotation produced robust support for a three-factor model (Accuracy, Speed, and Endurance) of SAM performance, which largely corresponded with existing theorized models of selective and sustained attention. Construct validity was evidenced by positive correlations between SAM Composite scores and all three SAM factors and IQ, and between SAM Accuracy and sequential memory. Value-added predictive validity was not confirmed through main effects of SAM on math performance above and beyond age and IQ; however, significant interactions by child sex were observed: Accuracy and Endurance both interacted with child sex to predict math performance. In both cases, the SAM factors predicted math performance more strongly for girls than for boys. There were no overall sex differences in SAM performance. In sum, the current findings suggest that interindividual variation in sustained selective attention, and potentially other aspects of attention and executive function, among young, high-risk children can be captured validly with developmentally sensitive measures.

  2. QTL and association analysis for skin and fibre pigmentation in sheep provides evidence of a major causative mutation and epistatic effects.

    PubMed

    Raadsma, H W; Jonas, E; Fleet, M R; Fullard, K; Gongora, J; Cavanagh, C R; Tammen, I; Thomson, P C

    2013-08-01

    The pursuits of white features and white fleeces free of pigmented fibre have been important selection objectives for many sheep breeds. The cause and inheritance of non-white colour patterns in sheep has been studied since the early 19th century. Discovery of genetic causes, especially those which predispose pigmentation in white sheep, may lead to more accurate selection tools for improved apparel wool. This article describes an extended QTL study for 13 skin and fibre pigmentation traits in sheep. A total of 19 highly significant, 10 significant and seven suggestive QTL were identified in a QTL mapping experiment using an Awassi × Merino × Merino backcross sheep population. All QTL on chromosome 2 exceeded a LOD score of greater than 4 (range 4.4-30.1), giving very strong support for a major gene for pigmentation on this chromosome. Evidence of epistatic interactions was found for QTL for four traits on chromosomes 2 and 19. The ovine TYRP1 gene on OAR 2 was sequenced as a strong positional candidate gene. A highly significant association (P < 0.01) of grandparental haplotypes across nine segregating SNP/microsatellite markers including one non-synonymous SNP with pigmentation traits could be shown. Up to 47% of the observed variation in pigmentation was accounted for by models using TYRP1 haplotypes and 83% for models with interactions between two QTL probabilities, offering scope for marker-assisted selection for these traits. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

  3. Population-genomic variation within RNA viruses of the Western honey bee, Apis mellifera, inferred from deep sequencing

    PubMed Central

    2013-01-01

    Background Deep sequencing of viruses isolated from infected hosts is an efficient way to measure population-genetic variation and can reveal patterns of dispersal and natural selection. In this study, we mined existing Illumina sequence reads to investigate single-nucleotide polymorphisms (SNPs) within two RNA viruses of the Western honey bee (Apis mellifera), deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). All viral RNA was extracted from North American samples of honey bees or, in one case, the ectoparasitic mite Varroa destructor. Results Coverage depth was generally lower for IAPV than DWV, and marked gaps in coverage occurred in several narrow regions (< 50 bp) of IAPV. These coverage gaps occurred across sequencing runs and were virtually unchanged when reads were re-mapped with greater permissiveness (up to 8% divergence), suggesting a recurrent sequencing artifact rather than strain divergence. Consensus sequences of DWV for each sample showed little phylogenetic divergence, low nucleotide diversity, and strongly negative values of Fu and Li’s D statistic, suggesting a recent population bottleneck and/or purifying selection. The Kakugo strain of DWV fell outside of all other DWV sequences at 100% bootstrap support. IAPV consensus sequences supported the existence of multiple clades as had been previously reported, and Fu and Li’s D was closer to neutral expectation overall, although a sliding-window analysis identified a significantly positive D within the protease region, suggesting selection maintains diversity in that region. Within-sample mean diversity was comparable between the two viruses on average, although for both viruses there was substantial variation among samples in mean diversity at third codon positions and in the number of high-diversity sites. FST values were bimodal for DWV, likely reflecting neutral divergence in two low-diversity populations, whereas IAPV had several sites that were strong outliers with very low FST. Conclusions This initial survey of genetic variation within honey bee RNA viruses suggests future directions for studies examining the underlying causes of population-genetic structure in these economically important pathogens. PMID:23497218

  4. Population-genomic variation within RNA viruses of the Western honey bee, Apis mellifera, inferred from deep sequencing.

    PubMed

    Cornman, Robert Scott; Boncristiani, Humberto; Dainat, Benjamin; Chen, Yanping; vanEngelsdorp, Dennis; Weaver, Daniel; Evans, Jay D

    2013-03-07

    Deep sequencing of viruses isolated from infected hosts is an efficient way to measure population-genetic variation and can reveal patterns of dispersal and natural selection. In this study, we mined existing Illumina sequence reads to investigate single-nucleotide polymorphisms (SNPs) within two RNA viruses of the Western honey bee (Apis mellifera), deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). All viral RNA was extracted from North American samples of honey bees or, in one case, the ectoparasitic mite Varroa destructor. Coverage depth was generally lower for IAPV than DWV, and marked gaps in coverage occurred in several narrow regions (< 50 bp) of IAPV. These coverage gaps occurred across sequencing runs and were virtually unchanged when reads were re-mapped with greater permissiveness (up to 8% divergence), suggesting a recurrent sequencing artifact rather than strain divergence. Consensus sequences of DWV for each sample showed little phylogenetic divergence, low nucleotide diversity, and strongly negative values of Fu and Li's D statistic, suggesting a recent population bottleneck and/or purifying selection. The Kakugo strain of DWV fell outside of all other DWV sequences at 100% bootstrap support. IAPV consensus sequences supported the existence of multiple clades as had been previously reported, and Fu and Li's D was closer to neutral expectation overall, although a sliding-window analysis identified a significantly positive D within the protease region, suggesting selection maintains diversity in that region. Within-sample mean diversity was comparable between the two viruses on average, although for both viruses there was substantial variation among samples in mean diversity at third codon positions and in the number of high-diversity sites. FST values were bimodal for DWV, likely reflecting neutral divergence in two low-diversity populations, whereas IAPV had several sites that were strong outliers with very low FST. This initial survey of genetic variation within honey bee RNA viruses suggests future directions for studies examining the underlying causes of population-genetic structure in these economically important pathogens.

  5. Diagnostic Yield of Routine Enteropathogenic Stool Tests in Pediatric Ulcerative Colitis.

    PubMed

    Ihekweazu, Faith D; Ajjarapu, Avanthi; Kellermayer, Richard

    2015-01-01

    It can be important to exclude infectious etiologies prior to adjusting immunosuppressive therapy in patients with ulcerative colitis (UC) exacerbation. We sought to determine the diagnostic yield of routine infectious stool studies in pediatric UC patients. We conducted a retrospective review of 152 pediatric UC patients at Texas Children's Hospital between January 2003 and December 2009. The patient records were followed through July 2014. The number and type of infectious stool studies performed and the results of those were collected. Three hundred fifty-four diagnostic stool tests were conducted for Clostridium difficile; 13.6% were positive. Two hundred twenty stool bacterial cultures were performed, and 1.8% were positive, all growing non-typhoid Salmonella. One of 13 (7.7%) Adenovirus PCR tests was positive. Two of 152 examinations (1.3%) for Ova and Parasites were positive. No stool tests for viral culture, viral particles, Yersinia or Rotavirus were positive. Clostridium difficile infection is common in pediatric UC, and routine screening during flares is strongly recommended. Other bacterial and parasitic infections routinely tested for are uncommon, but Salmonella may be a potentially important attribute to disease exacerbations in select patients. In patients without co-morbid conditions, the utility of performing non-specific fecal viral tests is questionable. © 2015 by the Association of Clinical Scientists, Inc.

  6. Phylogeny of marattioid ferns (Marattiaceae): inferring a root in the absence of a closely related outgroup.

    PubMed

    Murdock, Andrew G

    2008-05-01

    Closely related outgroups are optimal for rooting phylogenetic trees; however, such ideal outgroups are not always available. A phylogeny of the marattioid ferns (Marattiaceae), an ancient lineage with no close relatives, was reconstructed using nucleotide sequences of multiple chloroplast regions (rps4 + rps4-trnS spacer, trnS-trnG spacer + trnG intron, rbcL, atpB), from 88 collections, selected to cover the broadest possible range of morphologies and geographic distributions within the extant taxa. Because marattioid ferns are phylogenetically isolated from other lineages, and internal branches are relatively short, rooting was problematic. Root placement was strongly affected by long-branch attraction under maximum parsimony and by model choice under maximum likelihood. A multifaceted approach to rooting was employed to isolate the sources of bias and produce a consensus root position. In a statistical comparison of all possible root positions with three different outgroups, most root positions were not significantly less optimal than the maximum likelihood root position, including the consensus root position. This phylogeny has several important taxonomic implications for marattioid ferns: Marattia in the broad sense is paraphyletic; the Hawaiian endemic Marattia douglasii is most closely related to tropical American taxa; and Angiopteris is monophyletic only if Archangiopteris and Macroglossum are included.

  7. nNOS inhibition during profound asphyxia reduces seizure burden and improves survival of striatal phenotypic neurons in preterm fetal sheep.

    PubMed

    Drury, Paul P; Davidson, Joanne O; Mathai, Sam; van den Heuij, Lotte G; Ji, Haitao; Bennet, Laura; Tan, Sidhartha; Silverman, Richard B; Gunn, Alistair J

    2014-08-01

    Basal ganglia injury after hypoxia-ischemia remains common in preterm infants, and is closely associated with later cerebral palsy. In the present study we tested the hypothesis that a highly selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10, would improve survival of striatal phenotypic neurons after profound asphyxia, and that the subsequent seizure burden and recovery of EEG are associated with neural outcome. 24 chronically instrumented preterm fetal sheep were randomized to either JI-10 (3 ml of 0.022 mg/ml, n = 8) or saline (n = 8) infusion 15 min before 25 min complete umbilical cord occlusion, or saline plus sham-occlusion (n = 8). Umbilical cord occlusion was associated with reduced numbers of calbindin-28k-, GAD-, NPY-, PV-, Calretinin- and nNOS-positive striatal neurons (p < 0.05 vs. sham occlusion) but not ChAT-positive neurons. JI-10 was associated with increased numbers of calbindin-28k-, GAD-, nNOS-, NPY-, PV-, Calretinin- and ChAT-positive striatal neurons (p < 0.05 vs. saline + occlusion). Seizure burden was strongly associated with loss of calbindin-positive cells (p < 0.05), greater seizure amplitude was associated with loss of GAD-positive cells (p < 0.05), and with more activated microglia in the white matter tracts (p < 0.05). There was no relationship between EEG power after 7 days recovery and total striatal cell loss, but better survival of NPY-positive neurons was associated with lower EEG power. In summary, these findings suggest that selective nNOS inhibition during asphyxia is associated with protection of phenotypic striatal projection neurons and has potential to help reduce basal ganglia injury in some premature babies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Population genetics inference for longitudinally-sampled mutants under strong selection.

    PubMed

    Lacerda, Miguel; Seoighe, Cathal

    2014-11-01

    Longitudinal allele frequency data are becoming increasingly prevalent. Such samples permit statistical inference of the population genetics parameters that influence the fate of mutant variants. To infer these parameters by maximum likelihood, the mutant frequency is often assumed to evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process that requires the assumption that the forces of natural selection and mutation are weak. This assumption is not always appropriate. For example, mutations that impart drug resistance in pathogens may evolve under strong selective pressure. Here, we present an alternative approximation to the mutant-frequency distribution that does not make any assumptions about the magnitude of selection or mutation and is much more computationally efficient than the standard diffusion approximation. Simulation studies are used to compare the performance of our method to that of the Wright-Fisher and Gaussian diffusion approximations. For large populations, our method is found to provide a much better approximation to the mutant-frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum-likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when our method is used. This is further demonstrated with an application to mutant-frequency data from an experimental study of bacteriophage evolution. We therefore recommend our method for estimating the selection coefficient when the effective population size is too large to utilize the discrete Wright-Fisher model. Copyright © 2014 by the Genetics Society of America.

  9. The evolution of sexual size dimorphism in the house finch. II. Population divergence in relation to local selection.

    PubMed

    Badyaev, A V; Hill, G E; Stoehr, A M; Nolan, P M; McGraw, K J

    2000-12-01

    Recent colonization of ecologically distinct areas in North America by the house finch (Carpodacus mexicanus) was accompanied by strong population divergence in sexual size dimorphism. Here we examined whether this divergence was produced by population differences in local selection pressures acting on each sex. In a long-term study of recently established populations in Alabama, Michigan, and Montana, we examined three selection episodes for each sex: selection for pairing success, overwinter survival, and within-season fecundity. Populations varied in intensity of these selection episodes, the contribution of each episode to the net selection, and in the targets of selection. Direction and intensity of selection strongly differed between sexes, and different selection episodes often favored opposite changes in morphological traits. In each population, current net selection for sexual dimorphism was highly concordant with observed sexual dimorphism--in each population, selection for dimorphism was the strongest on the most dimorphic traits. Strong directional selection on sexually dimorphic traits, and similar intensities of selection in both sexes, suggest that in each of the recently established populations, both males and females are far from their local fitness optimum, and that sexual dimorphism has arisen from adaptive responses in both sexes. Population differences in patterns of selection on dimorphism, combined with both low levels of ontogenetic integration in heritable sexually dimorphic traits and sexual dimorphism in growth patterns, may account for the close correspondence between dimorphism in selection and observed dimorphism in morphology across house finch populations.

  10. Location of a major antigenic site involved in Ross River virus neutralization.

    PubMed

    Vrati, S; Fernon, C A; Dalgarno, L; Weir, R C

    1988-02-01

    The location of a major antigenic domain involved in the neutralization of an alphavirus, Ross River virus, has been defined in terms of its position in the amino acid sequence of the E2 glycoprotein. The domain encompasses three topographically close epitopes which were identified using three E2-specific neutralizing monoclonal antibodies in competitive binding assays. Nucleotide sequencing of the structural protein genes of monoclonal antibody-selected antigenic variants showed that for each variant there was a single nucleotide change in the E2 gene leading to a nonconservative amino acid substitution in E2. Changes were at positions 216, 234, and 246-251 in the amino acid sequence. The epitopes are in a region of E2 which, though not strongly conserved as to sequence among Ross River virus, Semliki Forest virus, and Sindbis virus, is conserved in its hydropathy profile among the three alphaviruses. The epitopes lie between two asparagine-linked glycosylation sites (residues 200 and 262) in E2. They are conserved as to position between the mouse virulent T48 strain and the mouse avirulent NB5092 strain.

  11. α-Defensins in the Prevention of HIV Transmission Among Breastfed Infants

    PubMed Central

    Kuhn, Louise; Trabattoni, Daria; Kankasa, Chipepo; Semrau, Katherine; Kasonde, Prisca; Lissoni, Francesca; Sinkala, Moses; Ghosh, Mrinal; Vwalika, Cheswa; Aldrovandi, Grace M.; Thea, Donald M.; Clerici, Mario

    2006-01-01

    Summary: α-Defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of α-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected HIV-positive women who did not transmit HIV to their infants was conducted in Lusaka, Zambia. α-Defensins were detected in most (79%) of the milk samples tested. Concentrations of α-defensins increased as breast milk HIV RNA quantity increased, and breast milk HIV RNA quantity was, in turn, a strong and significant predictor of HIV transmission. After adjustment for milk HIV RNA quantity, however, α-defensin concentration was significantly associated with a decreased risk of intrapartum and postnatal HIV transmission (odds ratio = 0.3, 95% confidence interval: 0.09-0.93). Our data suggest that there may be a role for α-defensins in prevention of HIV transmission to breastfed infants. PMID:15905728

  12. Sexual selection on morphological and physiological traits and fluctuating asymmetry in the black scavenger fly Sepsis cynipsea.

    PubMed

    Blanckenhorn, W U; Kraushaar, U R S; Teuschl, Y; Reim, C

    2004-05-01

    Previous univariate studies of the fly Sepsis cynipsea (Diptera: Sepsidae) have demonstrated spatiotemporally variable and consequently overall weak sexual selection favouring large male size, which is nevertheless stronger on average than fecundity selection favouring larger females. To identify specific target(s) of selection on body size and additional traits possibly affecting mating success, two multivariate field studies of sexual selection were conducted. In one study using seasonal replicates from three populations, we assessed 15 morphological traits. No clear targets of sexual selection on male size could be detected, perhaps because spatiotemporal variation in selection was again strong. In particular, there was no (current) selection on male abdomen length or fore coxa length, the only traits for which S. cynipsea males are not smaller than females. Interestingly, copulating males had a consistently shorter fore femur base, a secondary sexual trait, and a wider clasper (hypopygium) gap, an external genital trait. In a second study using daily and seasonal replicates from one population, we included physiological measures of energy reserves (lipids, glucose, glycogen), in addition to hind tibia length and fluctuating asymmetry (FA) of all pairs of legs. This study again confirmed the mating advantage of large males, and additionally suggests independent positive influences of lipids (the long-term energy stores), with effects of glucose and glycogen (the short-term energy stores) tending to be negative. FA of paired traits was not associated with male mating success. Our study suggests that inclusion of physiological measures and genital traits in phenomenological studies of selection, which is rare, would be fruitful in other species.

  13. Fish habitat selection in a large hydropeaking river: Strong individual and temporal variations revealed by telemetry.

    PubMed

    Capra, Hervé; Plichard, Laura; Bergé, Julien; Pella, Hervé; Ovidio, Michaël; McNeil, Eric; Lamouroux, Nicolas

    2017-02-01

    Modeling individual fish habitat selection in highly variable environments such as hydropeaking rivers is required for guiding efficient management decisions. We analyzed fish microhabitat selection in the heterogeneous hydraulic and thermal conditions (modeled in two-dimensions) of a reach of the large hydropeaking Rhône River locally warmed by the cooling system of a nuclear power plant. We used modern fixed acoustic telemetry techniques to survey 18 fish individuals (five barbels, six catfishes, seven chubs) signaling their position every 3s over a three-month period. Fish habitat selection depended on combinations of current microhabitat hydraulics (e.g. velocity, depth), past microhabitat hydraulics (e.g. dewatering risk or maximum velocities during the past 15days) and to a lesser extent substrate and temperature. Mixed-effects habitat selection models indicated that individual effects were often stronger than specific effects. In the Rhône, fish individuals appear to memorize spatial and temporal environmental changes and to adopt a "least constraining" habitat selection. Avoiding fast-flowing midstream habitats, fish generally live along the banks in areas where the dewatering risk is high. When discharge decreases, however, they select higher velocities but avoid both dewatering areas and very fast-flowing midstream habitats. Although consistent with the available knowledge on static fish habitat selection, our quantitative results demonstrate temporal variations in habitat selection, depending on individual behavior and environmental history. Their generality could be further tested using comparative experiments in different environmental configurations. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

    PubMed

    Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

    2016-10-01

    Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    PubMed

    Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

    2011-04-14

    Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

  16. Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

    PubMed Central

    Wang, Yin-qiu; Qian, Ya-ping; Yang, Su; Shi, Hong; Liao, Cheng-hong; Zheng, Hong-Kun; Wang, Jun; Lin, Alice A.; Cavalli-Sforza, L. Luca; Underhill, Peter A.; Chakraborty, Ranajit; Jin, Li; Su, Bing

    2005-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition. PMID:15834139

  17. Gender parity trends for invited speakers at four prominent virology conference series.

    PubMed

    Kalejta, Robert F; Palmenberg, Ann C

    2017-06-07

    Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers. IMPORTANCE Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The under representation of women as invited speakers at international scientific conferences exemplifies a present-day discussion topic usually occurring without facts to support or refute the arguments. We now provide records profiling four prominent virology conferences over the years 1982 to 2017 with the intention that the trends and accompanying analyses of the gender parity of invited speakers may allow the ongoing discussions to be informed. Copyright © 2017 American Society for Microbiology.

  18. Gender Parity Trends for Invited Speakers at Four Prominent Virology Conference Series

    PubMed Central

    Palmenberg, Ann C.

    2017-01-01

    ABSTRACT Scientific conferences are most beneficial to participants when they showcase significant new experimental developments, accurately summarize the current state of the field, and provide strong opportunities for collaborative networking. A top-notch slate of invited speakers, assembled by conference organizers or committees, is key to achieving these goals. The perceived underrepresentation of female speakers at prominent scientific meetings is currently a popular topic for discussion, but one that often lacks supportive data. We compiled the full rosters of invited speakers over the last 35 years for four prominent international virology conferences, the American Society for Virology Annual Meeting (ASV), the International Herpesvirus Workshop (IHW), the Positive-Strand RNA Virus Symposium (PSR), and the Gordon Research Conference on Viruses & Cells (GRC). The rosters were cross-indexed by unique names, gender, year, and repeat invitations. When plotted as gender-dependent trends over time, all four conferences showed a clear proclivity for male-dominated invited speaker lists. Encouragingly, shifts toward parity are emerging within all units, but at different rates. Not surprisingly, both selection of a larger percentage of first-time participants and the presence of a woman on the speaker selection committee correlated with improved parity. Session chair information was also collected for the IHW and GRC. These visible positions also displayed a strong male dominance over time that is eroding slowly. We offer our personal interpretation of these data to aid future organizers achieve improved equity among the limited number of available positions for session moderators and invited speakers. IMPORTANCE Politicians and media members have a tendency to cite anecdotes as conclusions without any supporting data. This happens so frequently now, that a name for it has emerged: fake news. Good science proceeds otherwise. The underrepresentation of women as invited speakers at international scientific conferences exemplifies a present-day discussion topic usually occurring without facts to support or refute the arguments. We now provide records profiling four prominent virology conferences over the years 1982 to 2017 with the intention that the trends and accompanying analyses of the gender parity of invited speakers may allow the ongoing discussions to be informed. PMID:28592542

  19. Predicting Volleyball Serve-Reception

    PubMed Central

    Paulo, Ana; Zaal, Frank T. J. M.; Fonseca, Sofia; Araújo, Duarte

    2016-01-01

    Serve and serve-reception performance have predicted success in volleyball. Given the impact of serve-reception on the game, we aimed at understanding what it is in the serve and receiver's actions that determines the selection of the type of pass used in serve-reception and its efficacy. Four high-level volleyball players received jump-float serves from four servers in two reception zones—zone 1 and 5. The ball and the receiver's head were tracked with two video cameras, allowing 3D world-coordinates reconstruction. Logistic-regression models were used to predict the type of pass used (overhand or underhand) and serve-reception efficacy (error, out, or effective) from variables related with the serve kinematics and related with the receiver's on-court positioning and movement. Receivers' initial position was different when in zone 1 and 5. This influenced the serve-related variables as well as the type of pass used. Strong predictors of using an underhand rather than overhand pass were higher ball contact of the server, reception in zone 1, receiver's initial position more to the back of the court and backward receiver movement. Receiver's larger longitudinal displacements and an initial position more to the back of the court had a strong relationship with the decreasing of the serve-reception efficacy. Receivers' positioning and movement were the factors with the largest impact on the type of pass used and the efficacy of the reception. Reception zone affected the variance in the ball's kinematics (with the exception of the ball's lateral displacement), as well as in the receivers' positioning (distances from the net and from the target). Also the reception zone was associated with the type of pass used by the receiver but not with reception efficacy. Given volleyball's rotation rule, the receiver needs to master receiving in the different reception zones; he/she needs to adapt to the diverse constraints of each zone to maintain performance efficacy. Thus, being able to flexibly vary positioning and passing, given local (zone) constraints, can yield an advantage in high-level volleyball serve-reception. Further, research needs to consider other serve modes (e.g., power-jump serve) and a full-court context of performance to support the present study's findings. PMID:27853442

  20. The Evolution of Vp1 Gene in Enterovirus C Species Sub-Group That Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

    PubMed Central

    Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

    2014-01-01

    Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific ‘signature’ amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific ‘signature’ amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared. PMID:24695547

  1. The evolution of Vp1 gene in enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

    PubMed

    Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

    2014-01-01

    Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific 'signature' amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific 'signature' amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared.

  2. An efficient route to selective bio-oxidation catalysts: an iterative approach comprising modeling, diversification, and screening, based on CYP102A1.

    PubMed

    Seifert, Alexander; Antonovici, Mihaela; Hauer, Bernhard; Pleiss, Jürgen

    2011-06-14

    Perillyl alcohol is the terminal hydroxylation product of the cheap and readily available terpene, limonene. It has high potential as an anti-tumor substance, but is of limited availability. In principle, cytochrome P450 monooxygenases, such as the self-sufficient CYP102A1, are promising catalysts for the oxidation of limonene or other inert hydrocarbons. The wild-type enzyme converts (4R)-limonene to four different oxidation products; however, terminal hydroxylation at the allylic C7 is not observed. Here we describe a generic strategy to engineer this widely used enzyme to hydroxylate exclusively the exposed, but chemically less reactive, primary C7 in the presence of other reactive positions. The approach presented here turns CYP102A1 into a highly selective catalyst with a shifted product spectra by successive rounds of modeling, the design of small focused libraries, and screening. In the first round a minimal CYP102A1 mutant library was rationally designed. It contained variants with improved or strongly shifted regio-, stereo- and chemoselectivity, compared to wild-type. From this library the variant with the highest perillyl alcohol ratio was fine-tuned by two additional rounds of molecular modeling, diversification, and screening. In total only 29 variants needed to be screened to identify the triple mutant A264V/A238V/L437F that converts (4R)-limonene to perillyl alcohol with a selectivity of 97 %. Focusing mutagenesis on a small number of relevant positions identified by computational approaches is the key for efficient screening for enzyme selectivity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Positive selection of digestive Cys proteases in herbivorous Coleoptera.

    PubMed

    Vorster, Juan; Rasoolizadeh, Asieh; Goulet, Marie-Claire; Cloutier, Conrad; Sainsbury, Frank; Michaud, Dominique

    2015-10-01

    Positive selection is thought to contribute to the functional diversification of insect-inducible protease inhibitors in plants in response to selective pressures exerted by the digestive proteases of their herbivorous enemies. Here we assessed whether a reciprocal evolutionary process takes place on the insect side, and whether ingestion of a positively selected plant inhibitor may translate into a measurable rebalancing of midgut proteases in vivo. Midgut Cys proteases of herbivorous Coleoptera, including the major pest Colorado potato beetle (Leptinotarsa decemlineata), were first compared using a codon-based evolutionary model to look for the occurrence of hypervariable, positively selected amino acid sites among the tested sequences. Hypervariable sites were found, distributed within -or close to- amino acid regions interacting with Cys-type inhibitors of the plant cystatin protein family. A close examination of L. decemlineata sequences indicated a link between their assignment to protease functional families and amino acid identity at positively selected sites. A function-diversifying role for positive selection was further suggested empirically by in vitro protease assays and a shotgun proteomic analysis of L. decemlineata Cys proteases showing a differential rebalancing of protease functional family complements in larvae fed single variants of a model cystatin mutated at positively selected amino acid sites. These data confirm overall the occurrence of hypervariable, positively selected amino acid sites in herbivorous Coleoptera digestive Cys proteases. They also support the idea of an adaptive role for positive selection, useful to generate functionally diverse proteases in insect herbivores ingesting functionally diverse, rapidly evolving dietary cystatins. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Invasion of Ancestral Mammals into Dim-light Environments Inferred from Adaptive Evolution of the Phototransduction Genes

    PubMed Central

    Wu, Yonghua; Wang, Haifeng; Hadly, Elizabeth A.

    2017-01-01

    Nocturnality is a key evolutionary innovation of mammals that enables mammals to occupy relatively empty nocturnal niches. Invasion of ancestral mammals into nocturnality has long been inferred from the phylogenetic relationships of crown Mammalia, which is primarily nocturnal, and crown Reptilia, which is primarily diurnal, although molecular evidence for this is lacking. Here we used phylogenetic analyses of the vision genes involved in the phototransduction pathway to predict the diel activity patterns of ancestral mammals and reptiles. Our results demonstrated that the common ancestor of the extant Mammalia was dominated by positive selection for dim-light vision, supporting the predominate nocturnality of the ancestral mammals. Further analyses showed that the nocturnality of the ancestral mammals was probably derived from the predominate diurnality of the ancestral amniotes, which featured strong positive selection for bright-light vision. Like the ancestral amniotes, the common ancestor of the extant reptiles and various taxa in Squamata, one of the main competitors of the temporal niches of the ancestral mammals, were found to be predominate diurnality as well. Despite this relatively apparent temporal niche partitioning between ancestral mammals and the relevant reptiles, our results suggested partial overlap of their temporal niches during crepuscular periods. PMID:28425474

  5. HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis.

    PubMed

    De Silvestri, Annalisa; Capittini, Cristina; Poddighe, Dimitri; Marseglia, Gian Luigi; Mascaretti, Luca; Bevilacqua, Elena; Scotti, Valeria; Rebuffi, Chiara; Pasi, Annamaria; Martinetti, Miryam; Tinelli, Carmine

    2017-12-01

    Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Detection of aflatoxin and surface mould contaminated figs by using Fourier transform near-infrared reflectance spectroscopy.

    PubMed

    Durmuş, Efkan; Güneş, Ali; Kalkan, Habil

    2017-01-01

    Aflatoxins are toxic metabolites that are mainly produced by members of the Aspergillus section Flavi on many agricultural products. Certain agricultural products such as figs are known to be high risk products for aflatoxin contamination. Aflatoxin contaminated figs may show a bright greenish yellow fluorescence (BGYF) under ultraviolet (UV) light at a wavelength of 365 nm. Traditionally, BGYF positive figs are manually selected by workers. However, manual selection depends on the expertise level of the workers and it may cause them skin-related health problems due to UV radiation. In this study, we propose a non-invasive approach to detect aflatoxin and surface mould contaminated figs by using Fourier transform near-infrared (FT-NIR) reflectance spectroscopy. A classification accuracy of 100% is achieved for classifying the figs into aflatoxin contaminated/uncontaminated and surface mould contaminated/uncontaminated categories. In addition, a strong correlation has been found between aflatoxin and surface mould. Combined with pattern classification methods, the NIR spectroscopy can be used to detect aflatoxin contaminated figs non-invasively. Furthermore, a positive correlation between surface mould and aflatoxin contamination leads to a promising alternative indicator for the detection of aflatoxin-contaminated figs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Nucleotide diversity, natural variation, and evolution of Flexible culm-1 and Strong culm-2 lodging resistance genes in rice.

    PubMed

    Rashid, Muhammad Abdul Rehman; Zhao, Yan; Zhang, Hongliang; Li, Jinjie; Li, Zichao

    2016-07-01

    Lodging resistance is one of the vital traits in yield improvement and sustainability. Culm wall thickness, diameter, and strength are different traits that can govern the lodging resistance in rice. The genes SCM2 and FC1 have been isolated for culm thickness, strength, and flexibility, but their functional nucleotide variations were still unknown. We used a 13× deep sequence of 795 diverse genotypes to present the functional variation and SNP diversity in SCM2 and FC1. The major functional variant for the SCM2 gene was at position 27480181 and for the FC1 gene at position 31072992. Haplotype analysis of both genes provided their various allelic differences among haplotypes. SCM2 alleles further presented the evolution of Oryza sativa L. subsp. indica and subsp. japonica genomes from common parent in different geographical zones, while the haplotypes of FC1 suggested their evolution from different strains of the common parent Oryza rufipogon. SCM2 showed purifying selection and functional associations with rare alleles, while FC1 displayed balanced selection favored by multiple heterozygous alleles. Genotypes with an allelic combination of SCM2-3 and FC1-2 in japonica background exhibited striking resistance against lodging, which can be used in further breeding programs.

  8. The effect of environmental harshness on neurogenesis: a large-scale comparison.

    PubMed

    Chancellor, Leia V; Roth, Timothy C; LaDage, Lara D; Pravosudov, Vladimir V

    2011-03-01

    Harsh environmental conditions may produce strong selection pressure on traits, such as memory, that may enhance fitness. Enhanced memory may be crucial for survival in animals that use memory to find food and, thus, particularly important in environments where food sources may be unpredictable. For example, animals that cache and later retrieve their food may exhibit enhanced spatial memory in harsh environments compared with those in mild environments. One way that selection may enhance memory is via the hippocampus, a brain region involved in spatial memory. In a previous study, we established a positive relationship between environmental severity and hippocampal morphology in food-caching black-capped chickadees (Poecile atricapillus). Here, we expanded upon this previous work to investigate the relationship between environmental harshness and neurogenesis, a process that may support hippocampal cytoarchitecture. We report a significant and positive relationship between the degree of environmental harshness across several populations over a large geographic area and (1) the total number of immature hippocampal neurons, (2) the number of immature neurons relative to the hippocampal volume, and (3) the number of immature neurons relative to the total number of hippocampal neurons. Our results suggest that hippocampal neurogenesis may play an important role in environments where increased reliance on memory for cache recovery is critical. Copyright © 2010 Wiley Periodicals, Inc.

  9. Association between mandibular retrognathia and TMJ disorders in adult females.

    PubMed

    Miller, James R; Burgess, Jeffrey A; Critchlow, Cathy W

    2004-01-01

    This study assesses the association between temporomandibular joint (TMJ) disorders and mandibular retrognathia. We conducted a case-control study among women, aged 18-70 years, recruited from Kaiser Permanente Northwest Division (KPNW, Portland, OR) and Group Health Cooperative of Puget Sound (GHC, Seattle, WA). Cases (N= 160) were women seeking treatment for TMJ disorders at KPNW and GHC clinics. Controls (N=151) were women without TMJ disorders, selected from among adult female dental hygiene patients at KPNW or GHC enrollees. Case status was determined by questionnaire; mandibular sagittal position (orthognathic, mildly retrognathic, severely retrognathic, or prognathic) was measured using digitized facial photographs. Odds ratios (OR) and associated 95 percent confidence intervals (CI) estimated the magnitude of the association between TMJ disorders and mandibular sagittal position. Women with TMJ disorders were 4.0 times (95% CI=1.5, 10.8) more likely than controls to have severe retrognathia; no association with mild retrognathia or prognathia was seen. Results were similar when cases were restricted to those with recent onset of TMJ pain (OR=6.3; 95% CI=1.8, 21.8). We found a strong association between TMJ disorders and severe mandibular retrognathia in adult females. In some women this likely resulted from TMJ disorders influencing mandibular development over time. However, among a subset of women, our data support the reverse hypothesis--that severe mandibular retrognathia may influence the development of TMJ disorders. Despite this strong association, abnormal mandibular position contributed only a small portion to the overall rate at which women sought treatment for TMJ disorders.

  10. A comparative evaluation of in vitro skin sensitisation tests: the human cell-line activation test (h-CLAT) versus the local lymph node assay (LLNA).

    PubMed

    Ashikaga, Takao; Sakaguchi, Hitoshi; Sono, Sakiko; Kosaka, Nanae; Ishikawa, Makie; Nukada, Yuko; Miyazawa, Masaaki; Ito, Yuichi; Nishiyama, Naohiro; Itagaki, Hiroshi

    2010-08-01

    We previously developed the human cell-line activation test (h-CLAT) in vitro skin sensitisation test, based on our reported finding that a 24-hour exposure of THP-1 cells (a human monocytic leukaemia cell line) to sensitisers is sufficient to induce the augmented expression of CD86 and CD54. The aim of this study is to confirm the predictive value of h-CLAT for skin sensitisation activity by employing a larger number of test chemicals. One hundred chemicals were selected, according to their categorisation in the local lymph node assay (LLNA), as being: extreme, strong, moderate and weak sensitisers, and non-sensitisers. The correlation of the h-CLAT results with the LLNA results was 84%. There were some false negatives (e.g. benzoyl peroxide, hexyl cinnamic aldehyde) and some false positives (e.g. 1-bromobutane, diethylphthalate). Eight out of the 9 false negatives (89%) were water-insoluble chemicals. The h-CLAT could positively predict not only extreme and strong sensitisers, but also moderate and weak sensitisers, though the detection rates of weak sensitisers and non-sensitisers were comparatively low. Some sensitisers enhanced both CD86 and CD54 levels, and some enhanced the level of only one of them. The use of the combination of CD86 and CD54 induction as a positive indicator, improved the accuracy of the test. In conclusion, the h-CLAT is expected to be a useful cell-based in vitro method for predicting skin sensitisation potential. 2010 FRAME.

  11. Background parenchymal enhancement in preoperative breast MRI.

    PubMed

    Kohara, Satoko; Ishigaki, Satoko; Satake, Hiroko; Kawamura, Akiko; Kawai, Hisashi; Kikumori, Toyone; Naganawa, Shinji

    2015-08-01

    We aimed to assess the influence of background parenchymal enhancement (BPE) on surgical planning performed using preoperative MRI for breast cancer evaluation. Between January 2009 and December 2010, 91 newly diagnosed breast cancer patients (mean age, 55.5 years; range, 30-88 years) who underwent preoperative bilateral breast MRI followed by planned breast conservation therapy were retrospectively enrolled. MRI was performed to assess the tumor extent in addition to mammography and breast ultrasonography. BPE in the contralateral normal breast MRI at the early dynamic phase was visually classified as follows: minimal (n=49), mild (n=27), moderate (n=7), and marked (n=8). The correlations between the BPE grade and age, menopausal status, index tumor size, changes in surgical management based on MRI results, positive predictive value (PPV) of MRI, and surgical margins were assessed. Patients in the strong BPE groups were significantly younger (p=0.002) and generally premenopausal (p<0.001). Surgical treatment was not changed in 67 cases (73.6%), while extended excision and mastectomy were performed in 12 cases (13.2%), each based on additional lesions on MRI. Six of 79 (7.6%) patients who underwent breast conservation therapy had tumor-positive resection margins. In cases where surgical management was changed, the PPV for MRI-detected foci was high in the minimal (91.7%) and mild groups (66.7%), and 0% in the moderate and marked groups (p=0.002). Strong BPE causes false-positive MRI findings and may lead to overly extensive surgery, whereas MRI may be beneficial in select patients with weak BPE.

  12. Assessing the chemotaxis behavior of Physarum polycephalum to a range of simple volatile organic chemicals.

    PubMed

    de Lacy Costello, Ben P J; Adamatzky, Andrew I

    2013-09-01

    The chemotaxis behavior of the plasmodial stage of the true slime mold Physarum Polycephalum was assessed when given a binary choice between two volatile organic chemicals (VOCs) placed in its environment. All possible binary combinations were tested between 19 separate VOCs selected due to their prevalence and biological activity in common plant and insect species. The slime mold exhibited positive chemotaxis toward a number of VOCs with the following order of preference:   Farnesene > β-myrcene > tridecane > limonene > p-cymene > 3-octanone > β-pinene > m-cresol > benzylacetate > cis-3-hexenylacetate. For the remaining compounds, no positive chemotaxis was observed in any of the experiments, and for most compounds there was an inhibitory effect on the growth of the slime mold. By assessing this lack of growth or failure to propagate, it was possible to produce a list of compounds ranked in terms of their inhibitory effect: nonanal > benzaldehyde > methylbenzoate > linalool > methyl-p-benzoquinone > eugenol > benzyl alcohol > geraniol > 2-phenylethanol. This analysis shows a distinct preference of the slime mold for non-oxygenated terpene and terpene-like compounds (farnesene, β-myrcene, limonene, p-cymene and β-pinene). In contrast, terpene-based alcohols such as geraniol and linalool were found to have a strong inhibitory effect on the slime mold. Both the aldehydes utilized in this study had the strongest inhibitory effect on the slime mold of all the 19 VOCs tested. Interestingly, 3-octanone, which has a strong association with a "fungal odor," was the only compound with an oxygenated functionality where Physarum Polycephalum exhibits distinct positive chemotaxis.

  13. Assessing the chemotaxis behavior of Physarum polycephalum to a range of simple volatile organic chemicals

    PubMed Central

    de Lacy Costello, Ben P.J.; Adamatzky, Andrew I.

    2013-01-01

    The chemotaxis behavior of the plasmodial stage of the true slime mold Physarum Polycephalum was assessed when given a binary choice between two volatile organic chemicals (VOCs) placed in its environment. All possible binary combinations were tested between 19 separate VOCs selected due to their prevalence and biological activity in common plant and insect species. The slime mold exhibited positive chemotaxis toward a number of VOCs with the following order of preference:   Farnesene > β-myrcene > tridecane > limonene > p-cymene > 3-octanone > β-pinene > m-cresol > benzylacetate > cis-3-hexenylacetate. For the remaining compounds, no positive chemotaxis was observed in any of the experiments, and for most compounds there was an inhibitory effect on the growth of the slime mold. By assessing this lack of growth or failure to propagate, it was possible to produce a list of compounds ranked in terms of their inhibitory effect: nonanal > benzaldehyde > methylbenzoate > linalool > methyl-p-benzoquinone > eugenol > benzyl alcohol > geraniol > 2-phenylethanol. This analysis shows a distinct preference of the slime mold for non-oxygenated terpene and terpene-like compounds (farnesene, β-myrcene, limonene, p-cymene and β-pinene). In contrast, terpene-based alcohols such as geraniol and linalool were found to have a strong inhibitory effect on the slime mold. Both the aldehydes utilized in this study had the strongest inhibitory effect on the slime mold of all the 19 VOCs tested. Interestingly, 3-octanone, which has a strong association with a “fungal odor,” was the only compound with an oxygenated functionality where Physarum Polycephalum exhibits distinct positive chemotaxis. PMID:24265848

  14. Effect of Phytoplankton Richness on Phytoplankton Biomass Is Weak Where the Distribution of Herbivores is Patchy.

    PubMed

    Weis, Jerome J

    2016-01-01

    Positive effects of competitor species richness on competitor productivity can be more pronounced at a scale that includes heterogeneity in 'bottom-up' environmental factors, such as the supply of limiting nutrients. The effect of species richness is not well understood in landscapes where variation in 'top-down' factors, such as the abundance of predators or herbivores, has a strong influence competitor communities. I asked how phytoplankton species richness directly influenced standing phytoplankton biomass in replicate microcosm regions where one patch had a population of herbivores (Daphnia pulicaria) and one patch did not have herbivores. The effect of phytoplankton richness on standing phytoplankton biomass was positive but weak and not statistically significant at this regional scale. Among no-Daphnia patches, there was a significant positive effect of phytoplankton richness that resulted from positive selection effects for two dominant and productive species in polycultures. Among with-Daphnia patches there was not a significant effect of phytoplankton richness. The same two species dominated species-rich polycultures in no- and with-Daphnia patches but both species were relatively vulnerable to consumption by Daphnia. Consistent with previous studies, this experiment shows a measurable positive influence of primary producer richness on biomass when herbivores were absent. It also shows that given the patchy distribution of herbivores at a regional scale, a regional positive effect was not detected.

  15. Effect of Phytoplankton Richness on Phytoplankton Biomass Is Weak Where the Distribution of Herbivores is Patchy

    PubMed Central

    Weis, Jerome J.

    2016-01-01

    Positive effects of competitor species richness on competitor productivity can be more pronounced at a scale that includes heterogeneity in ‘bottom-up’ environmental factors, such as the supply of limiting nutrients. The effect of species richness is not well understood in landscapes where variation in ‘top-down’ factors, such as the abundance of predators or herbivores, has a strong influence competitor communities. I asked how phytoplankton species richness directly influenced standing phytoplankton biomass in replicate microcosm regions where one patch had a population of herbivores (Daphnia pulicaria) and one patch did not have herbivores. The effect of phytoplankton richness on standing phytoplankton biomass was positive but weak and not statistically significant at this regional scale. Among no-Daphnia patches, there was a significant positive effect of phytoplankton richness that resulted from positive selection effects for two dominant and productive species in polycultures. Among with-Daphnia patches there was not a significant effect of phytoplankton richness. The same two species dominated species-rich polycultures in no- and with-Daphnia patches but both species were relatively vulnerable to consumption by Daphnia. Consistent with previous studies, this experiment shows a measurable positive influence of primary producer richness on biomass when herbivores were absent. It also shows that given the patchy distribution of herbivores at a regional scale, a regional positive effect was not detected. PMID:27196376

  16. A systematic review of the diagnostic performance of orthopedic physical examination tests of the hip

    PubMed Central

    2013-01-01

    Background Previous reviews of the diagnostic performances of physical tests of the hip in orthopedics have drawn limited conclusions because of the low to moderate quality of primary studies published in the literature. This systematic review aims to build on these reviews by assessing a broad range of hip pathologies, and employing a more selective approach to the inclusion of studies in order to accurately gauge diagnostic performance for the purposes of making recommendations for clinical practice and future research. It specifically identifies tests which demonstrate strong and moderate diagnostic performance. Methods A systematic search of Medline, Embase, Embase Classic and CINAHL was conducted to identify studies of hip tests. Our selection criteria included an analysis of internal and external validity. We reported diagnostic performance in terms of sensitivity, specificity, predictive values and likelihood ratios. Likelihood ratios were used to identify tests with strong and moderate diagnostic utility. Results Only a small proportion of tests reported in the literature have been assessed in methodologically valid primary studies. 16 studies were included in our review, producing 56 independent test-pathology combinations. Two tests demonstrated strong clinical utility, the patellar-pubic percussion test for excluding radiologically occult hip fractures (negative LR 0.05, 95% Confidence Interval [CI] 0.03-0.08) and the hip abduction sign for diagnosing sarcoglycanopathies in patients with known muscular dystrophies (positive LR 34.29, 95% CI 10.97-122.30). Fifteen tests demonstrated moderate diagnostic utility for diagnosing and/or excluding hip fractures, symptomatic osteoarthritis and loosening of components post-total hip arthroplasty. Conclusions We have identified a number of tests demonstrating strong and moderate diagnostic performance. These findings must be viewed with caution as there are concerns over the methodological quality of the primary studies from which we have extracted our data. Future studies should recruit larger, representative populations and allow for the construction of complete 2×2 contingency tables. PMID:23987589

  17. A systematic review of the diagnostic performance of orthopedic physical examination tests of the hip.

    PubMed

    Rahman, Labib Ataur; Adie, Sam; Naylor, Justine Maree; Mittal, Rajat; So, Sarah; Harris, Ian Andrew

    2013-08-30

    Previous reviews of the diagnostic performances of physical tests of the hip in orthopedics have drawn limited conclusions because of the low to moderate quality of primary studies published in the literature. This systematic review aims to build on these reviews by assessing a broad range of hip pathologies, and employing a more selective approach to the inclusion of studies in order to accurately gauge diagnostic performance for the purposes of making recommendations for clinical practice and future research. It specifically identifies tests which demonstrate strong and moderate diagnostic performance. A systematic search of Medline, Embase, Embase Classic and CINAHL was conducted to identify studies of hip tests. Our selection criteria included an analysis of internal and external validity. We reported diagnostic performance in terms of sensitivity, specificity, predictive values and likelihood ratios. Likelihood ratios were used to identify tests with strong and moderate diagnostic utility. Only a small proportion of tests reported in the literature have been assessed in methodologically valid primary studies. 16 studies were included in our review, producing 56 independent test-pathology combinations. Two tests demonstrated strong clinical utility, the patellar-pubic percussion test for excluding radiologically occult hip fractures (negative LR 0.05, 95% Confidence Interval [CI] 0.03-0.08) and the hip abduction sign for diagnosing sarcoglycanopathies in patients with known muscular dystrophies (positive LR 34.29, 95% CI 10.97-122.30). Fifteen tests demonstrated moderate diagnostic utility for diagnosing and/or excluding hip fractures, symptomatic osteoarthritis and loosening of components post-total hip arthroplasty. We have identified a number of tests demonstrating strong and moderate diagnostic performance. These findings must be viewed with caution as there are concerns over the methodological quality of the primary studies from which we have extracted our data. Future studies should recruit larger, representative populations and allow for the construction of complete 2×2 contingency tables.

  18. Identification of positive selection in disease response genes within members of the Poaceae.

    PubMed

    Rech, Gabriel E; Vargas, Walter A; Sukno, Serenella A; Thon, Michael R

    2012-12-01

    Millions of years of coevolution between plants and pathogens can leave footprints on their genomes and genes involved on this interaction are expected to show patterns of positive selection in which novel, beneficial alleles are rapidly fixed within the population. Using information about upregulated genes in maize during Colletotrichum graminicola infection and resources available in the Phytozome database, we looked for evidence of positive selection in the Poaceae lineage, acting on protein coding sequences related with plant defense. We found six genes with evidence of positive selection and another eight with sites showing episodic selection. Some of them have already been described as evolving under positive selection, but others are reported here for the first time including genes encoding isocitrate lyase, dehydrogenases, a multidrug transporter, a protein containing a putative leucine-rich repeat and other proteins with unknown functions. Mapping positively selected residues onto the predicted 3-D structure of proteins showed that most of them are located on the surface, where proteins are in contact with other molecules. We present here a set of Poaceae genes that are likely to be involved in plant defense mechanisms and have evidence of positive selection. These genes are excellent candidates for future functional validation.

  19. Organizational culture in cardiovascular care in Chinese hospitals: a descriptive cross-sectional study.

    PubMed

    Yin, Emily S; Downing, Nicholas S; Li, Xi; Singer, Sara J; Curry, Leslie A; Li, Jing; Krumholz, Harlan M; Jiang, Lixin

    2015-12-21

    Organizational learning, the process by which a group changes its behavior in response to newly acquired knowledge, is critical to outstanding organizational performance. In hospitals, strong organizational learning culture is linked with improved health outcomes for patients. This study characterizes the organizational learning culture of hospitals in China from the perspective of a cardiology service. Using a modified Abbreviated Learning Organization Survey (27 questions), we characterized organizational learning culture in a nationally representative sample of 162 Chinese hospitals, selecting 2 individuals involved with cardiovascular care at each hospital. Responses were analyzed at the hospital level by calculating the average of the two responses to each question. Responses were categorized as positive if they were 5+ on a 7-point scale or 4+ on a 5-point scale. Univariate and multiple regression analyses were used to assess the relationship between selected hospital characteristics and perceptions of organizational learning culture. Of the 324 participants invited to take the survey, 316 responded (98 % response rate). Perceptions of organizational learning culture varied among items, among domains, and both among and within hospitals. Overall, the median proportion of positive responses was 82 % (interquartile range = 59 % to 93 %). "Training," "Performance Monitoring," and "Leadership that Reinforces Learning" were characterized as the most favorable domains, while "Time for Reflection" was the least favorable. Multiple regression analyses showed that region was the only factor significantly correlated with overall positive response rate. This nationally representative survey demonstrated variation in hospital organizational learning culture among hospitals in China. The variation was not substantially explained by hospital characteristics. Organizational learning culture domains with lower positive response rates reveal important areas for improvement.

  20. The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma.

    PubMed

    Wong, Andrew T; Shao, Meng; Rineer, Justin; Lee, Anna; Schwartz, David; Schreiber, David

    2017-06-01

    The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy ± postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node-positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins.

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