Sample records for positive selection effects

  1. Selective Control of Attention Supports the Positivity Effect in Aging

    PubMed Central

    Sasse, Laura K.; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

    2014-01-01

    There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging. PMID:25093459

  2. Selective control of attention supports the positivity effect in aging.

    PubMed

    Sasse, Laura K; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

    2014-01-01

    There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

  3. 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.

  4. Is There a Paradox of Aging: When the Negative Aging Stereotype Meets the Positivity Effect in Older Adults.

    PubMed

    Zhou, Liqing; Lu, Jia; Chen, Guopeng; Dong, Li; Yao, Yujia

    2017-01-01

    Background/Study Context: Socioemotional selectivity theory (SST) states that the positivity effect is a result of older adults' emotion regulation and that older adults derive more emotional satisfaction from prioritizing positive information processing. The authors explored whether the positivity effect appeared when the negative aging stereotype was activated in older adults and also whether the effect differed between mixed and unmixed valence conditions. Sixty younger (18-23 years of age) and 60 older (60-87 years of age) adults were randomly assigned to a control group and a priming group, in which the negative aging stereotype was activated. All the participants were asked to select 15 words that best described the elderly from a mixed-word list (positive and negative words were mixed together) and from an unmixed-word list (positive and negative words were separated). Older adults in the control group selected more positive words, whereas among younger adults, selection did not differ by valence in either the mixed- or unmixed-word list conditions. There were no differences between the positive and negative word choices of the younger and older adults in the priming group. We calculated the differences between the numbers of positive and negative words, and the differences in the older adults' word choices were larger than those among the younger adults; the differences were also larger in the control group than in the priming group. The positivity effect worked by choosing positive stimuli rather than avoiding negative stimuli. The role of emotion regulation in older adults was limited, and when the positivity effect faced the effect of the negative aging stereotype, the negative stereotype effect was dominant. Future research should explore the changes in the positivity effect in the face of a positive aging stereotype and what roles other factors (e.g., activation level of the stereotype, arousal level of affective words) might play.

  5. SWITCHING TRANSMITTER POSITIONING OF SYNCHROS

    DOEpatents

    Wolff, H.

    1962-03-13

    A transformer apparatus is designed for effecting the step positioning of synchro motors. The apparatus is provided with ganged switches and pre- selected contacts to permit the units and tens selection of the desired angular position for the synchro motor rotor with only the movement of two selector knobs required. With the selection thus made, the appropriate pre-selected signal is delivered to the synchro motor for positioning the rotor of the latter as selected. The transformer apparatus is divided into smaller arrangements to conform with coraputed trigonometric relations which will give the desired results. (AEC)

  6. 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.

  7. Synergistic effect of acidity and extraframework position in faujasite on renewable p-xylene production

    PubMed Central

    2018-01-01

    p-Xylene is a commodity chemical used for the manufacture of plastic bottles and textiles. For the biomass-based route from 2,5-dimethylfuran (DMF) and ethylene, the properties of the catalyst such as acidity effect, product selectivity and catalyst activity play an important role. To determine the effect of acidity and extraframework position in faujasite zeolite on p-xylene selectivity, type Y (Si/Al = 40 and Si/Al = 2.55) and X (Si/Al = 1.25) zeolites containing the extraframework Lewis acids Na+, K+, Li+, Ag+ and Cu+, and a Brønsted acid-containing zeolite, HY (Si/Al = 40), were prepared and tested for p-xylene production under solvent-free conditions and at low conversions (less than 35%). Here it is reported that NaX zeolite catalyses DMF and ethylene conversion to p-xylene with 91% selectivity at 30% conversion, which is better than the 25% p-xylene selectivity obtained when using HY at similar conversion. ANOVA was used to show that there is a synergistic effect between acidity and extraframework position on the rate of p-xylene production. At 7% DMF conversion, Lewis acids were more selective than the Brønsted acid tested (50 versus 30% p-xylene selectivity). p-Xylene selectivity is optimal when using Lewis acids with moderate acidity and extraframework positions located in the faujasite supercage (sites II and III). PMID:29892435

  8. Estimating the parameters of background selection and selective sweeps in Drosophila in the presence of gene conversion

    PubMed Central

    Campos, José Luis; Charlesworth, Brian

    2017-01-01

    We used whole-genome resequencing data from a population of Drosophila melanogaster to investigate the causes of the negative correlation between the within-population synonymous nucleotide site diversity (πS) of a gene and its degree of divergence from related species at nonsynonymous nucleotide sites (KA). By using the estimated distributions of mutational effects on fitness at nonsynonymous and UTR sites, we predicted the effects of background selection at sites within a gene on πS and found that these could account for only part of the observed correlation between πS and KA. We developed a model of the effects of selective sweeps that included gene conversion as well as crossing over. We used this model to estimate the average strength of selection on positively selected mutations in coding sequences and in UTRs, as well as the proportions of new mutations that are selectively advantageous. Genes with high levels of selective constraint on nonsynonymous sites were found to have lower strengths of positive selection and lower proportions of advantageous mutations than genes with low levels of constraint. Overall, background selection and selective sweeps within a typical gene reduce its synonymous diversity to ∼75% of its value in the absence of selection, with larger reductions for genes with high KA. Gene conversion has a major effect on the estimates of the parameters of positive selection, such that the estimated strength of selection on favorable mutations is greatly reduced if it is ignored. PMID:28559322

  9. The happy spotlight: positive mood and selective attention to rewarding information.

    PubMed

    Tamir, Maya; Robinson, Michael D

    2007-08-01

    Positive mood states are thought to sensitize individuals to rewards in their environment, presumably in the service of approach-related decision making and behavior. From a selective attention standpoint, such mood-related effects should be associated with selective attention biases favoring rewarding stimuli. No prior results along these lines have been reported. Therefore, the authors conducted a systematic program of research designed to document such relations. Study 1 found that daily positive mood states were associated with attention to reward words in a spatial probe task. Studies 2-5 replicated this association in the context of mood manipulations. The latter studies also show that the effect generalizes across different mood manipulation procedures, is specific to positive mood states, and is particularly apparent in relation to rewarding (vs. non-rewarding) positive stimuli. The results extend our knowledge of mood-cognition relations and have important implications for understanding the social cognitive consequences of positive mood states.

  10. Deep sequencing in library selection projects: what insight does it bring?

    PubMed

    Glanville, J; D'Angelo, S; Khan, T A; Reddy, S T; Naranjo, L; Ferrara, F; Bradbury, A R M

    2015-08-01

    High throughput sequencing is poised to change all aspects of the way antibodies and other binders are discovered and engineered. Millions of available sequence reads provide an unprecedented sampling depth able to guide the design and construction of effective, high quality naïve libraries containing tens of billions of unique molecules. Furthermore, during selections, high throughput sequencing enables quantitative tracing of enriched clones and position-specific guidance to amino acid variation under positive selection during antibody engineering. Successful application of the technologies relies on specific PCR reagent design, correct sequencing platform selection, and effective use of computational tools and statistical measures to remove error, identify antibodies, estimate diversity, and extract signatures of selection from the clone down to individual structural positions. Here we review these considerations and discuss some of the remaining challenges to the widespread adoption of the technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Deep sequencing in library selection projects: what insight does it bring?

    PubMed Central

    Glanville, J; D’Angelo, S; Khan, T.A.; Reddy, S. T.; Naranjo, L.; Ferrara, F.; Bradbury, A.R.M.

    2015-01-01

    High throughput sequencing is poised to change all aspects of the way antibodies and other binders are discovered and engineered. Millions of available sequence reads provide an unprecedented sampling depth able to guide the design and construction of effective, high quality naïve libraries containing tens of billions of unique molecules. Furthermore, during selections, high throughput sequencing enables quantitative tracing of enriched clones and position-specific guidance to amino acid variation under positive selection during antibody engineering. Successful application of the technologies relies on specific PCR reagent design, correct sequencing platform selection, and effective use of computational tools and statistical measures to remove error, identify antibodies, estimate diversity, and extract signatures of selection from the clone down to individual structural positions. Here we review these considerations and discuss some of the remaining challenges to the widespread adoption of the technology. PMID:26451649

  12. 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.

  13. Selective positioning and integration of individual single-walled carbon nanotubes.

    PubMed

    Jiao, Liying; Xian, Xiaojun; Wu, Zhongyun; Zhang, Jin; Liu, Zhongfan

    2009-01-01

    We present a general selective positioning and integration technique for fabricating single-walled carbon nanotube (SWNT) circuits with preselected individual SWNTs as building blocks by utilizing poly(methyl methacrylate) (PMMA) thin film as a macroscopically handlable mediator. The transparency and marker-replicating capability of PMMA mediator allow the selective placement of chirality-specific nanotubes onto predesigned patterned surfaces with a resolution of ca. 1 mum. This technique is compatible with multiple operations and p-n conversion by chemical doping, which enables the construction of complex and logic circuits. As demonstrations of building SWNTs circuits, we fabricated a field effect inverter, a 2 x 2 all-SWNT crossbar field effect transistor (FET), and flexible FETs on plastic with this technique. This selective positioning approach can also be extended to construct purpose-directed architecture with various nanoscale building blocks.

  14. 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

  15. Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds

    PubMed Central

    Dean, Rebecca; Harrison, Peter W.; Wright, Alison E.; Zimmer, Fabian; Mank, Judith E.

    2015-01-01

    The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. PMID:26067773

  16. Does Navigation Always Predict Performance? Effects of Navigation on Digital Reading Are Moderated by Comprehension Skills

    ERIC Educational Resources Information Center

    Naumann, Johannes; Salmerón, Ladislao

    2016-01-01

    This study investigated interactive effects of navigation and offline comprehension skill on digital reading performance. As indicators of navigation, relevant page selection and irrelevant page selection were considered. In 533 Spanish high school students aged 11-17 positive effects of offline comprehension skill and relevant page selection on…

  17. The Relevance of Emotional Intelligence in Personnel Selection for High Emotional Labor Jobs

    PubMed Central

    Hock, Michael; Schütz, Astrid

    2016-01-01

    Although a large number of studies have pointed to the potential of emotional intelligence (EI) in the context of personnel selection, research in real-life selection contexts is still scarce. The aim of the present study was to examine whether EI would predict Assessment Center (AC) ratings of job-relevant competencies in a sample of applicants for the position of a flight attendant. Applicants’ ability to regulate emotions predicted performance in group exercises. However, there were inconsistent effects of applicants’ ability to understand emotions: Whereas the ability to understand emotions had a positive effect on performance in interview and role play, the effect on performance in group exercises was negative. We suppose that the effect depends on task type and conclude that tests of emotional abilities should be used judiciously in personnel selection procedures. PMID:27124201

  18. Impact of Surface Type, Wheelchair Weight, and Axle Position on Wheelchair Propulsion by Novice Older Adults

    PubMed Central

    Cowan, Rachel E.; Nash, Mark S.; Collinger, Jennifer L.; Koontz, Alicia M.; Boninger, Michael L.

    2009-01-01

    Objective To examine the impact of surface type, wheelchair weight, and rear axle position on older adult propulsion biomechanics. Design Crossover trial. Setting Biomechanics laboratory. Participants Convenience sample of 53 ambulatory older adults with minimal wheelchair experience (65−87y); men = 20, women = 33. Intervention Participants propelled 4 different wheelchair configurations over 4 surfaces; tile, low carpet, high carpet, and an 8% grade ramp (surface, chair order randomized). Chair configurations included: (1) unweighted chair with an anterior axle position, (2) 9.05kg weighted chair with an anterior axle position, (3) unweighted chair with a posterior axle position (Δ0.08m), and (4) 9.05kg weighted chair with a posterior axle position (Δ0.08m). Weight was added to a titanium folding chair, simulating the weight difference between very light and depot wheelchairs. Instrumented wheels measured propulsion kinetics. Main Outcome Measures Average self-selected velocity, push-frequency, stroke length, peak resultant and tangential force. Results Velocity decreased as surface rolling resistance or chair weight increased. Peak resultant and tangential forces increased as chair weight increased, surface resistance increased, and with a posterior axle position. The effect of a posterior axle position was greater on high carpet and the ramp. The effect of weight was constant, but more easily observed on high carpet and ramp. The effects of axle position and weight were independent of one another. Conclusion Increased surface resistance decreases self-selected velocity and increases peak forces. Increased weight decreases self-selected velocity and increases forces. Anterior axle positions decrease forces, more so on high carpet. Effects of weight and axle position are independent. Greatest reductions in peak forces occur in lighter chairs with anterior axle positions. PMID:19577019

  19. Inferring Selection on Amino Acid Preference in Protein Domains

    PubMed Central

    Durbin, Richard

    2009-01-01

    Models that explicitly account for the effect of selection on new mutations have been proposed to account for “codon bias” or the excess of “preferred” codons that results from selection for translational efficiency and/or accuracy. In principle, such models can be applied to any mutation that results in a preferred allele, but in most cases, the fitness effect of a specific mutation cannot be predicted. Here we show that it is possible to assign preferred and unpreferred states to amino acid changing mutations that occur in protein domains. We propose that mutations that lead to more common amino acids (at a given position in a domain) can be considered “preferred alleles” just as are synonymous mutations leading to codons for more abundant tRNAs. We use genome-scale polymorphism data to show that alleles for preferred amino acids in protein domains occur at higher frequencies in the population, as has been shown for preferred codons. We show that this effect is quantitative, such that there is a correlation between the shift in frequency of preferred alleles and the predicted fitness effect. As expected, we also observe a reduction in the numbers of polymorphisms and substitutions at more important positions in domains, consistent with stronger selection at those positions. We examine the derived allele frequency distribution and polymorphism to divergence ratios of preferred and unpreferred differences and find evidence for both negative and positive selections acting to maintain protein domains in the human population. Finally, we analyze a model for selection on amino acid preferences in protein domains and find that it is consistent with the quantitative effects that we observe. PMID:19095755

  20. Inference of epistatic effects in a key mitochondrial protein

    NASA Astrophysics Data System (ADS)

    Nelson, Erik D.; Grishin, Nick V.

    2018-06-01

    We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein—cytochrome c oxidase subunit 2—for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2 N s ≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.

  1. 5 CFR 330.609 - Exceptions to CTAP selection priority.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... position change of a surplus or displaced employee in the local commuting area; (n) Effect a position..., including all extensions; (d) Reassign agency employees between or among positions in the local commuting... an excepted service appointment under part 213 of this chapter; (f) Effect a personnel action under...

  2. 5 CFR 330.609 - Exceptions to CTAP selection priority.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... position change of a surplus or displaced employee in the local commuting area; (n) Effect a position..., including all extensions; (d) Reassign agency employees between or among positions in the local commuting... an excepted service appointment under part 213 of this chapter; (f) Effect a personnel action under...

  3. Automatic and controlled attentional orienting in the elderly: A dual-process view of the positivity effect.

    PubMed

    Gronchi, G; Righi, S; Pierguidi, L; Giovannelli, F; Murasecco, I; Viggiano, M P

    2018-04-01

    The positivity effect in the elderly consists of an attentional preference for positive information as well as avoidance of negative information. Extant theories predict either that the positivity effect depends on controlled attentional processes (socio-emotional selectivity theory), or on an automatic gating selection mechanism (dynamic integration theory). This study examined the role of automatic and controlled attention in the positivity effect. Two dot-probe tasks (with the duration of the stimuli lasting 100 ms and 500 ms, respectively) were employed to compare the attentional bias of 35 elderly people to that of 35 young adults. The stimuli used were expressive faces displaying neutral, disgusted, fearful, and happy expressions. In comparison to young people, the elderly allocated more attention to happy faces at 100 ms and they tended to avoid fearful faces at 500 ms. The findings are not predicted by either theory taken alone, but support the hypothesis that the positivity effect in the elderly is driven by two different processes: an automatic attention bias toward positive stimuli, and a controlled mechanism that diverts attention away from negative stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Identification of new antibacterial targets in RNA polymerase of Mycobacterium tuberculosis by detecting positive selection sites.

    PubMed

    Wang, QingBiao; Xu, Yiqin; Gu, Zhuoya; Liu, Nian; Jin, Ke; Li, Yao; Crabbe, M James C; Zhong, Yang

    2018-04-01

    Bacterial RNA polymerase (RNAP) is an effective target for antibacterial treatment. In order to search new potential targets in RNAP of Mycobacterium, we detected adaptive selections of RNAP related genes in 13 strains of Mycobacterium by phylogenetic analysis. We first collected sequences of 17 genes including rpoA, rpoB, rpoC, rpoZ, and sigma factor A-M. Then maximum likelihood trees were constructed, followed by positive selection detection. We found that sigG shows positive selection along the clade (M. tuberculosis, M. bovis), suggesting its important evolutionary role and its potential to be a new antibacterial target. Moreover, the regions near 933Cys and 935His on the rpoB subunit of M. tuberculosis showed significant positive selection, which could also be a new attractive target for anti-tuberculosis drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The cardiovascular pharmacology of ICI 170777 ((6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4- thiadiazin-2-one) a novel compound with positive inotropic and vasodilator effects.

    PubMed Central

    Collis, M. G.; Keddie, J. R.; Rouse, W.

    1989-01-01

    1. This paper describes the cardiovascular effects of ICI 170777, a novel compound which enhances cardiac contractility and causes arterial and venous dilatation. 2. The positive inotropic effects of ICI 170777 on the heart were demonstrated by an increase in left ventricular dP/dtmax in the anaesthetized and conscious dog, and by an increase in tension development in isolated papillary muscles from the cat. 3. In the anaesthetized dog, the positive inotropic effects of ICI 170777 and of isoprenaline were attenuated by atenolol (5 mg kg-1, i.v.). Atenolol displaced the dose-response curve to ICI 170777 to the right by 4 fold but displaced the isoprenaline dose-response curve to the right by 247 fold. In vitro, however, atenolol (10 microM) had no significant effect on the positive inotropic response to ICI 170777. In the ganglion-blocked anaesthetized dog, infusion of a low dose of ICI 170777 which had no effect on the basal left ventricular dP/dtmax, selectively potentiated the positive inotropic effects of isoprenaline. These results indicate that ICI 170777 has both a non-adrenoceptor-mediated positive inotropic effect on the heart and also facilitates the beta-adrenoceptor-mediated control of contractility. 4. In the denervated and perfused hind-limb of the dog, ICI 170777 reduced arterial perfusion pressure and increased limb circumference at a constant arterial flow and venous pressure. This indicates that ICI 170777 has direct dilator actions on both arterial and venous vessels. In this preparation, diazoxide exerted an arterial selective vasodilator effect and sodium nitroprusside was a relatively selective venous dilator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2758224

  6. 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.

  7. 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).

  8. Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences.

    PubMed

    Colonna, Vincenza; Ayub, Qasim; Chen, Yuan; Pagani, Luca; Luisi, Pierre; Pybus, Marc; Garrison, Erik; Xue, Yali; Tyler-Smith, Chris; Abecasis, Goncalo R; Auton, Adam; Brooks, Lisa D; DePristo, Mark A; Durbin, Richard M; Handsaker, Robert E; Kang, Hyun Min; Marth, Gabor T; McVean, Gil A

    2014-06-30

    Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

  9. Views of the Self and Others at Different Ages: Utility of Repertory Grid Technique in Detecting the Positivity Effect in Aging

    ERIC Educational Resources Information Center

    Williams, Ben D.; Harter, Stephanie Lewis

    2010-01-01

    Socioemotional selectivity theory (Carstensen, 1995) posits a "positivity effect" in older adults, describing an increasing tendency to attend to, process, interpret, and remember events and others in life in a positive fashion as one ages. Drawing on personal construct theory, Viney (1993) observes increasing integration of constructions of self…

  10. Selective arylation and vinylation at the α position of vinylarenes.

    PubMed

    Zou, Yinjun; Qin, Liena; Ren, Xinfeng; Lu, Yunpeng; Li, Yongxin; Zhou, Jianrong Steve

    2013-03-04

    In intermolecular Heck reactions of styrene and vinylarenes, the aryl and vinyl groups routinely insert at the β position. However, selective insertion at the α position has been very rare. Herein, we provide a missing piece in the palette of Heck reaction, which gave >20:1 α selectivity. The key to our success is a new ferrocene 1,1'-bisphosphane (dnpf) that carries 1-naphthyl groups. Our mechanistic studies revealed that the high α selectivity is partly attributable to the steric effect of dnpf. The rigid and bulky 1-naphthyl groups of dnpf sterically disfavor β insertion. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Robotic vehicle

    DOEpatents

    Box, W. Donald

    1998-01-01

    A robotic vehicle for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle.

  12. Robotic vehicle

    DOEpatents

    Box, W. Donald

    1997-01-01

    A robotic vehicle for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle.

  13. Natural Selection in the Great Apes

    PubMed Central

    Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M.

    2016-01-01

    Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. PMID:27795229

  14. Learning to select useful landmarks.

    PubMed

    Greiner, R; Isukapalli, R

    1996-01-01

    To navigate effectively, an autonomous agent must be able to quickly and accurately determine its current location. Given an initial estimate of its position (perhaps based on dead-reckoning) and an image taken of a known environment, our agent first attempts to locate a set of landmarks (real-world objects at known locations), then uses their angular separation to obtain an improved estimate of its current position. Unfortunately, some landmarks may not be visible, or worse, may be confused with other landmarks, resulting in both time wasted in searching for the undetected landmarks, and in further errors in the agent's estimate of its position. To address these problems, we propose a method that uses previous experiences to learn a selection function that, given the set of landmarks that might be visible, returns the subset that can be used to reliably provide an accurate registration of the agent's position. We use statistical techniques to prove that the learned selection function is, with high probability, effectively at a local optimum in the space of such functions. This paper also presents empirical evidence, using real-world data, that demonstrate the effectiveness of our approach.

  15. Age-related perspectives and emotion processing.

    PubMed

    Lynchard, Nicholas A; Radvansky, Gabriel A

    2012-12-01

    Emotion is processed differently in younger and older adults. Older adults show a positivity effect, whereas younger adults show a negativity effect. Socioemotional selectivity theory suggests that these effects can be elicited in any age group when age-related perspectives are manipulated. To examine this, younger and older adults were oriented to actual and age-contrasting possible selves. Emotion activations were assessed using lexical decision. In line with socioemotional selectivity theory, shifts in emotion orientation varied according to perspective, with both younger and older adults showing a negativity effect when a younger adult perspective was taken and a positivity effect when an older adult perspective was taken. 2013 APA, all rights reserved

  16. Positive Selection Underlies Faster-Z Evolution of Gene Expression in Birds.

    PubMed

    Dean, Rebecca; Harrison, Peter W; Wright, Alison E; Zimmer, Fabian; Mank, Judith E

    2015-10-01

    The elevated rate of evolution for genes on sex chromosomes compared with autosomes (Fast-X or Fast-Z evolution) can result either from positive selection in the heterogametic sex or from nonadaptive consequences of reduced relative effective population size. Recent work in birds suggests that Fast-Z of coding sequence is primarily due to relaxed purifying selection resulting from reduced relative effective population size. However, gene sequence and gene expression are often subject to distinct evolutionary pressures; therefore, we tested for Fast-Z in gene expression using next-generation RNA-sequencing data from multiple avian species. Similar to studies of Fast-Z in coding sequence, we recover clear signatures of Fast-Z in gene expression; however, in contrast to coding sequence, our data indicate that Fast-Z in expression is due to positive selection acting primarily in females. In the soma, where gene expression is highly correlated between the sexes, we detected Fast-Z in both sexes, although at a higher rate in females, suggesting that many positively selected expression changes in females are also expressed in males. In the gonad, where intersexual correlations in expression are much lower, we detected Fast-Z for female gene expression, but crucially, not males. This suggests that a large amount of expression variation is sex-specific in its effects within the gonad. Taken together, our results indicate that Fast-Z evolution of gene expression is the product of positive selection acting on recessive beneficial alleles in the heterogametic sex. More broadly, our analysis suggests that the adaptive potential of Z chromosome gene expression may be much greater than that of gene sequence, results which have important implications for the role of sex chromosomes in speciation and sexual selection. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Thinking about a limited future enhances the positivity of younger and older adults' recall: Support for socioemotional selectivity theory.

    PubMed

    Barber, Sarah J; Opitz, Philipp C; Martins, Bruna; Sakaki, Michiko; Mather, Mara

    2016-08-01

    Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the "positivity effect," and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants' recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults' recall is typically more positive than younger adults' recall may index naturally shifting time horizons and goals with age.

  18. Potent and selective oxytocin receptor agonists without disulfide bridges.

    PubMed

    Adachi, Yusuke; Sakimura, Katsuya; Shimizu, Yuji; Nakayama, Masaharu; Terao, Yasuko; Yano, Takahiko; Asami, Taiji

    2017-06-01

    Oxytocin (OT) is a neuropeptide involved in a wide variety of physiological actions, both peripherally and centrally. Many human studies have revealed the potential of OT to treat autism spectrum disorders and schizophrenia. OT interacts with the OT receptor (OTR) as well as vasopressin 1a and 1b receptors (V 1a R, V 1b R) as an agonist, and agonistic activity for V 1a R and V 1b R may have a negative impact on the therapeutic effects of OTR agonism in the CNS. An OTR-selective agonistic peptide, FE 202767, in which the structural differences from OT are a sulfide bond instead of a disulfide bond, and N-alkylglycine replacement for Pro at position 7, was reported. However, the effects of amino acid substitutions in OT have not been comprehensively investigated to compare OTR, V 1a R, and V 1b R activities. This led us to obtain a new OTR-selective analog by comprehensive amino acid substitutions of OT and replacement of the disulfide bond. A systematic amino acid scanning (Ala, Leu, Phe, Ser, Glu, or Arg) of desamino OT (dOT) at positions 2, 3, 4, 5, 7, and 8 revealed the tolerability for the substitution at positions 7 and 8. Further detailed study showed that trans-4-hydroxyproline (trans-Hyp) at position 7 and γ-methylleucine [Leu(Me)] at position 8 were markedly effective for improving receptor selectivity without decreasing the potency at the OTR. Subsequently, a combination of these amino acid substitutions with the replacement of the disulfide bond of dOT analogs with a sulfide bond (carba analog) or an amide bond (lactam analog) yielded several promising analogs, including carba-1-[trans-Hyp 7 ,Leu(Me) 8 ]dOT (14) with a higher potency (7.2pM) at OTR than that of OT and marked selectivity (>10,000-fold) over V 1a R and V 1b R. Hence, we investigated comprehensive modification of OT and obtained new OT analogs that exhibited high potency at OTR with marked selectivity. These OTR-selective agonists could be useful to investigate OTR-mediated effects on psychiatric disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Challenges Women Face in Leadership Positions and Organizational Effectiveness: An Investigation

    ERIC Educational Resources Information Center

    Elmuti, Dean; Jia, Heather; Davis, Henry H.

    2009-01-01

    This study was undertaken to discover working public thoughts about roles of United States women in leadership positions and to test the relationship between managerial leadership styles and organizational effectiveness. A survey of perceptions of leadership roles and effectiveness distributed 700 randomly selected entities from industries in the…

  20. 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.

  1. Robotic vehicle

    DOEpatents

    Box, W.D.

    1997-02-11

    A robotic vehicle is described for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle. 20 figs.

  2. Robotic vehicle

    DOEpatents

    Box, W.D.

    1998-08-11

    A robotic vehicle is described for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendible appendages, each of which is radially extendible relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendible members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle. 20 figs.

  3. Multi-instance learning based on instance consistency for image retrieval

    NASA Astrophysics Data System (ADS)

    Zhang, Miao; Wu, Zhize; Wan, Shouhong; Yue, Lihua; Yin, Bangjie

    2017-07-01

    Multiple-instance learning (MIL) has been successfully utilized in image retrieval. Existing approaches cannot select positive instances correctly from positive bags which may result in a low accuracy. In this paper, we propose a new image retrieval approach called multiple instance learning based on instance-consistency (MILIC) to mitigate such issue. First, we select potential positive instances effectively in each positive bag by ranking instance-consistency (IC) values of instances. Then, we design a feature representation scheme, which can represent the relationship among bags and instances, based on potential positive instances to convert a bag into a single instance. Finally, we can use a standard single-instance learning strategy, such as the support vector machine, for performing object-based image retrieval. Experimental results on two challenging data sets show the effectiveness of our proposal in terms of accuracy and run time.

  4. 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.

  5. 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.

  6. The prospects of selection for social genetic effects to improve welfare and productivity in livestock

    PubMed Central

    Ellen, Esther D.; Rodenburg, T. Bas; Albers, Gerard A. A.; Bolhuis, J. Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F.; Muir, William M.; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A. M.; Visscher, Jeroen; Bijma, Piter

    2014-01-01

    Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock. PMID:25426136

  7. The prospects of selection for social genetic effects to improve welfare and productivity in livestock.

    PubMed

    Ellen, Esther D; Rodenburg, T Bas; Albers, Gerard A A; Bolhuis, J Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F; Muir, William M; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A M; Visscher, Jeroen; Bijma, Piter

    2014-01-01

    Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock.

  8. The Relation between Recombination Rate and Patterns of Molecular Evolution and Variation in Drosophila melanogaster

    PubMed Central

    Campos, José L.; Halligan, Daniel L.; Haddrill, Penelope R.; Charlesworth, Brian

    2014-01-01

    Genetic recombination associated with sexual reproduction increases the efficiency of natural selection by reducing the strength of Hill–Robertson interference. Such interference can be caused either by selective sweeps of positively selected alleles or by background selection (BGS) against deleterious mutations. Its consequences can be studied by comparing patterns of molecular evolution and variation in genomic regions with different rates of crossing over. We carried out a comprehensive study of the benefits of recombination in Drosophila melanogaster, both by contrasting five independent genomic regions that lack crossing over with the rest of the genome and by comparing regions with different rates of crossing over, using data on DNA sequence polymorphisms from an African population that is geographically close to the putatively ancestral population for the species, and on sequence divergence from a related species. We observed reductions in sequence diversity in noncrossover (NC) regions that are inconsistent with the effects of hard selective sweeps in the absence of recombination. Overall, the observed patterns suggest that the recombination rate experienced by a gene is positively related to an increase in the efficiency of both positive and purifying selection. The results are consistent with a BGS model with interference among selected sites in NC regions, and joint effects of BGS, selective sweeps, and a past population expansion on variability in regions of the genome that experience crossing over. In such crossover regions, the X chromosome exhibits a higher rate of adaptive protein sequence evolution than the autosomes, implying a Faster-X effect. PMID:24489114

  9. 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.

  10. 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.

  11. Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB₂R selective benzimidazoles reveal unexpected intrinsic properties.

    PubMed

    Nimczick, Martin; Pemp, Daniela; Darras, Fouad H; Chen, Xinyu; Heilmann, Jörg; Decker, Michael

    2014-08-01

    The design of bivalent ligands targeting G protein-coupled receptors (GPCRs) often leads to the development of new, highly selective and potent compounds. To date, no bivalent ligands for the human cannabinoid receptor type 2 (hCB₂R) of the endocannabinoid system (ECS) are described. Therefore, two sets of homobivalent ligands containing as parent structure the hCB2R selective agonist 13a and coupled at different attachment positions were synthesized. Changes of the parent structure at these positions have a crucial effect on the potency and efficacy of the ligands. However, we discovered that bivalency has an influence on the effect at both cannabinoid receptors. Moreover, we found out that the spacer length and the attachment position altered the efficacy of the bivalent ligands at the receptors by turning agonists into antagonists and inverse agonists. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Thinking about a Limited Future Enhances the Positivity of Younger and Older Adults’ Recall: Support for Socioemotional Selectivity Theory

    PubMed Central

    Barber, Sarah J.; Opitz, Philipp C.; Martins, Bruna; Sakaki, Michiko; Mather, Mara

    2016-01-01

    Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants’ recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults’ recall is typically more positive than younger adults’ recall may index naturally shifting time horizons and goals with age. PMID:27112461

  13. Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622.

    PubMed

    Uslaner, Jason M; Kuduk, Scott D; Wittmann, Marion; Lange, Henry S; Fox, Steve V; Min, Chris; Pajkovic, Natasa; Harris, Dawn; Cilissen, Caroline; Mahon, Chantal; Mostoller, Kate; Warrington, Steve; Beshore, Douglas C

    2018-06-01

    The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at developing selective M 1 muscarinic receptor activators. In this work, we describe the preclinical and clinical pharmacodynamic effects of the M 1 muscarinic receptor-positive allosteric modulator, MK-7622. MK-7622 attenuated the cognitive-impairing effects of the muscarinic receptor antagonist scopolamine and altered quantitative electroencephalography (qEEG) in both rhesus macaque and human. For both scopolamine reversal and qEEG, the effective exposures were similar between species. However, across species the minimum effective exposures to attenuate the scopolamine impairment were lower than for qEEG. Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus versus human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in humans for a selective M 1 muscarinic receptor-positive allosteric modulator. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Genomic selection in plant breeding.

    PubMed

    Newell, Mark A; Jannink, Jean-Luc

    2014-01-01

    Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

  15. Characterization of Angiotensin II Molecular Determinants Involved in AT1 Receptor Functional Selectivity.

    PubMed

    Domazet, Ivana; Holleran, Brian J; Richard, Alexandra; Vandenberghe, Camille; Lavigne, Pierre; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

    2015-06-01

    The octapeptide angiotensin II (AngII) exerts a variety of cardiovascular effects through the activation of the AngII type 1 receptor (AT1), a G protein-coupled receptor. The AT1 receptor engages and activates several signaling pathways, including heterotrimeric G proteins Gq and G12, as well as the extracellular signal-regulated kinases (ERK) 1/2 pathway. Additionally, following stimulation, βarrestin is recruited to the AT1 receptor, leading to receptor desensitization. It is increasingly recognized that specific ligands selectively bind and favor the activation of some signaling pathways over others, a concept termed ligand bias or functional selectivity. A better understanding of the molecular basis of functional selectivity may lead to the development of better therapeutics with fewer adverse effects. In the present study, we developed assays allowing the measurement of six different signaling modalities of the AT1 receptor. Using a series of AngII peptide analogs that were modified in positions 1, 4, and 8, we sought to better characterize the molecular determinants of AngII that underlie functional selectivity of the AT1 receptor in human embryonic kidney 293 cells. The results reveal that position 1 of AngII does not confer functional selectivity, whereas position 4 confers a bias toward ERK signaling over Gq signaling, and position 8 confers a bias toward βarrestin recruitment over ERK activation and Gq signaling. Interestingly, the analogs modified in position 8 were also partial agonists of the protein kinase C (PKC)-dependent ERK pathway via atypical PKC isoforms PKCζ and PKCι. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Teacher Praise: Maximizing the Motivational Impact. Teaching Strategies.

    ERIC Educational Resources Information Center

    McVey, Mary D.

    2001-01-01

    Recognizes the influence of praise on human behavior, and provides specific suggestions on how to maximize the positive effects of praise when intended as positive reinforcement. Examines contingency, specificity, and selectivity aspects of praise. Cautions teachers to avoid the controlling effects of praise and the possibility that praise may…

  17. 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).

  18. Evolutionary genetic analyses of MEF2C gene: implications for learning and memory in Homo sapiens.

    PubMed

    Kalmady, Sunil V; Venkatasubramanian, Ganesan; Arasappa, Rashmi; Rao, Naren P

    2013-02-01

    MEF2C facilitates context-dependent fear conditioning (CFC) which is a salient aspect of hippocampus-dependent learning and memory. CFC might have played a crucial role in human evolution because of its advantageous influence on survival of species. In this study, we analyzed 23 orthologous mammalian gene sequences of MEF2C gene to examine the evidence for positive selection on this gene in Homo sapiens using Phylogenetic Analysis by Maximum Likelihood (PAML) and HyPhy software. Both PAML Bayes Empirical Bayes (BEB) and HyPhy Fixed Effects Likelihood (FEL) analyses supported significant positive selection on 4 codon sites in H. sapiens. Also, haplotter analysis revealed significant ongoing positive selection on this gene in Central European population. The study findings suggest that adaptive selective pressure on this gene might have influenced human evolution. Further research on this gene might unravel the potential role of this gene in learning and memory as well as its pathogenetic effect in certain hippocampal disorders with evolutionary basis like schizophrenia. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Facilitating Creative Idea Selection: The Combined Effects of Self-Affirmation, Promotion Focus and Positive Affect

    ERIC Educational Resources Information Center

    de Buisonjé, David R.; Ritter, Simone M.; de Bruin, Suze; ter Horst, J. Marie-Louise; Meeldijk, Arne

    2017-01-01

    Generating creative ideas in a brainstorm session `is a crucial part of innovation. However, for actual implementation, the most creative ideas must be selected from a pool of ideas. To date, idea selection has remained relatively unexplored and validated instruments to measure idea selection performance are not systematically employed. This study…

  20. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    PubMed

    Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J

    2018-01-01

    Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  1. 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.

  2. When is selective self-presentation effective? An investigation of the moderation effects of "self-esteem" and "social trust".

    PubMed

    Kim, Yoonkyung; Baek, Young Min

    2014-11-01

    This study investigates the relationship between selective self-presentation and online life satisfaction, and how this relationship is influenced by respondents' perceptions of "self" (operationalized by "self-esteem") and "others" (operationalized by "social trust"). Relying on survey data from 712 Korean online users, two important findings were detected in our study. First, the positive relationship between selective self-presentation and online life satisfaction becomes more prominent among people with low self-esteem compared to those with high self-esteem, and second, this positive relationship is enhanced among people with high levels of social trust compared to those with low trust levels. Theoretical and practical implications of our findings as well as potential limitations are discussed.

  3. Chiral catalysts immobilized on achiral polymers: effect of the polymer support on the performance of the catalyst.

    PubMed

    Altava, Belén; Burguete, M Isabel; García-Verdugo, Eduardo; Luis, Santiago V

    2018-04-23

    Positive effects of the polymeric support on the performance of supported chiral catalysts, in terms of activity, stability and selectivity-enantioselectivity, have been reported when the support is properly selected and optimized opening the way to the design of more efficient catalytic systems.

  4. Positive selection drives faster-Z evolution in silkmoths

    PubMed Central

    Sackton, Timothy B.; Corbett-Detig, Russell B.; Nagaraju, Javaregowda; Vaishna, R. Lakshmi; Arunkumar, Kallare P.; Hartl, Daniel L.

    2014-01-01

    Genes linked to X or Z chromosomes, which are hemizygous in the heterogametic sex, are predicted to evolve at different rates than those on autosomes. This “faster-X effect” can arise either as a consequence of hemizygosity, which leads to more efficient selection for recessive beneficial mutations in the heterogametic sex, or as a consequence of reduced effective population size of the hemizygous chromosome, which leads to increased fixation of weakly deleterious mutations due to genetic drift. Empirical results to date suggest that, while the overall pattern across taxa is complicated, systems with male-heterogamy show a faster-X effect attributable to more efficient selection, while the faster-Z effect in female-heterogametic taxa is attributable to increased drift. To test the generality of the faster-Z pattern seen in birds and snakes, we sequenced the genome of the Lepidopteran silkmoth Bombyx huttoni. We show that silkmoths experience faster-Z evolution, but unlike in birds and snakes, the faster-Z effect appears to be attributable to more efficient positive selection. These results suggest that female-heterogamy alone is unlikely to explain the reduced efficacy of selection on the bird Z chromosome. It is likely that many factors, including differences in overall effective population size, influence Z chromosome evolution. PMID:24826901

  5. Demand effects on positive response distortion by police officer applicants on the Revised NEO Personality Inventory.

    PubMed

    Detrick, Paul; Chibnall, John T; Call, Cynthia

    2010-09-01

    Understanding and detecting response distortion is important in the high-demand circumstances of personnel selection. In this article, we describe positive response distortion on the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992) among police officer applicants under high and low demand conditions. Positive response distortion primarily reflected denial/minimization of Neuroticism and accentuation of traits associated with moralistic bias (Agreeableness and Conscientiousness). Validity of the NEO PI-R research validity scale, Positive Presentation Management, was weakly supported with respect to the Neuroticism domain only. Results will be useful in interpreting personality inventory results in the police personnel selection process.

  6. 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

  7. Penis size interacts with body shape and height to influence male attractiveness.

    PubMed

    Mautz, Brian S; Wong, Bob B M; Peters, Richard A; Jennions, Michael D

    2013-04-23

    Compelling evidence from many animal taxa indicates that male genitalia are often under postcopulatory sexual selection for characteristics that increase a male's relative fertilization success. There could, however, also be direct precopulatory female mate choice based on male genital traits. Before clothing, the nonretractable human penis would have been conspicuous to potential mates. This observation has generated suggestions that human penis size partly evolved because of female choice. Here we show, based upon female assessment of digitally projected life-size, computer-generated images, that penis size interacts with body shape and height to determine male sexual attractiveness. Positive linear selection was detected for penis size, but the marginal increase in attractiveness eventually declined with greater penis size (i.e., quadratic selection). Penis size had a stronger effect on attractiveness in taller men than in shorter men. There was a similar increase in the positive effect of penis size on attractiveness with a more masculine body shape (i.e., greater shoulder-to-hip ratio). Surprisingly, larger penis size and greater height had almost equivalent positive effects on male attractiveness. Our results support the hypothesis that female mate choice could have driven the evolution of larger penises in humans. More broadly, our results show that precopulatory sexual selection can play a role in the evolution of genital traits.

  8. Penis size interacts with body shape and height to influence male attractiveness

    PubMed Central

    Mautz, Brian S.; Wong, Bob B. M.; Peters, Richard A.; Jennions, Michael D.

    2013-01-01

    Compelling evidence from many animal taxa indicates that male genitalia are often under postcopulatory sexual selection for characteristics that increase a male’s relative fertilization success. There could, however, also be direct precopulatory female mate choice based on male genital traits. Before clothing, the nonretractable human penis would have been conspicuous to potential mates. This observation has generated suggestions that human penis size partly evolved because of female choice. Here we show, based upon female assessment of digitally projected life-size, computer-generated images, that penis size interacts with body shape and height to determine male sexual attractiveness. Positive linear selection was detected for penis size, but the marginal increase in attractiveness eventually declined with greater penis size (i.e., quadratic selection). Penis size had a stronger effect on attractiveness in taller men than in shorter men. There was a similar increase in the positive effect of penis size on attractiveness with a more masculine body shape (i.e., greater shoulder-to-hip ratio). Surprisingly, larger penis size and greater height had almost equivalent positive effects on male attractiveness. Our results support the hypothesis that female mate choice could have driven the evolution of larger penises in humans. More broadly, our results show that precopulatory sexual selection can play a role in the evolution of genital traits. PMID:23569234

  9. Data-driven region-of-interest selection without inflating Type I error rate.

    PubMed

    Brooks, Joseph L; Zoumpoulaki, Alexia; Bowman, Howard

    2017-01-01

    In ERP and other large multidimensional neuroscience data sets, researchers often select regions of interest (ROIs) for analysis. The method of ROI selection can critically affect the conclusions of a study by causing the researcher to miss effects in the data or to detect spurious effects. In practice, to avoid inflating Type I error rate (i.e., false positives), ROIs are often based on a priori hypotheses or independent information. However, this can be insensitive to experiment-specific variations in effect location (e.g., latency shifts) reducing power to detect effects. Data-driven ROI selection, in contrast, is nonindependent and uses the data under analysis to determine ROI positions. Therefore, it has potential to select ROIs based on experiment-specific information and increase power for detecting effects. However, data-driven methods have been criticized because they can substantially inflate Type I error rate. Here, we demonstrate, using simulations of simple ERP experiments, that data-driven ROI selection can indeed be more powerful than a priori hypotheses or independent information. Furthermore, we show that data-driven ROI selection using the aggregate grand average from trials (AGAT), despite being based on the data at hand, can be safely used for ROI selection under many circumstances. However, when there is a noise difference between conditions, using the AGAT can inflate Type I error and should be avoided. We identify critical assumptions for use of the AGAT and provide a basis for researchers to use, and reviewers to assess, data-driven methods of ROI localization in ERP and other studies. © 2016 Society for Psychophysiological Research.

  10. 5 CFR 330.609 - Exceptions to CTAP selection priority.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... employee in the local commuting area; (n) Effect a position change of an employee under 5 U.S.C. 8337 or..., including all extensions; (d) Reassign agency employees between or among positions in the local commuting... Federal Career Intern Program; (f) Effect a personnel action under, or specifically in lieu of, part 351...

  11. Selective skepticism: American and Chinese children's reasoning about evaluative academic feedback.

    PubMed

    Heyman, Gail D; Fu, Genyue; Lee, Kang

    2013-03-01

    Children's reasoning about the credibility of positive and negative evaluations of academic performance was examined. Across 2 studies, 7- and 10-year-olds from the United States and China (N = 334) judged the credibility of academic evaluations that were directed toward an unfamiliar peer. In Study 1, participants from China responded that criticism should be accepted to a greater extent than did participants from the United States, and children from both countries demonstrated a selective skepticism effect by treating negative feedback more skeptically than positive feedback. Study 2 replicated the selective skepticism effect among children from both countries and ruled out the possibility that it can be explained as a rational analysis of perceived base rates. The results suggest that children are selective in their trust of evaluative feedback and that their credibility judgments may be influenced by the desirability of the information that is being conveyed or its anticipated consequences.

  12. Enzyme-like specificity in zeolites: a unique site position in mordenite for selective carbonylation of methanol and dimethyl ether with CO.

    PubMed

    Boronat, Mercedes; Martínez-Sánchez, Cristina; Law, David; Corma, Avelino

    2008-12-03

    The mechanism of methanol carbonylation at different positions of zeolite MOR is investigated by quantum-chemical methods in order to discover which are the active sites that can selectively catalyze the desired reaction. It is shown that when methanol carbonylation competes with hydrocarbon formation, the first reaction occurs preferentially within 8MR channels. However, the unique selectivity for the carbonylation of methanol and dimethyl ether in mordenite is not only due to the size of the 8MR channel: neither process occurs equally at the two T3-O31 and T3-O33 positions. We show that only the T3-O33 positions are selective and that this selectivity is due to the unusual orientation of the methoxy group in relation to the 8MR channel (parallel to the cylinder axis). Only in this situation does the transition state for the attack of CO fit perfectly in the 8MR channel, while the reaction with methanol or DME is sterically impeded. This result explains why T3-O31, while also located in the 8MR channel of mordenite, is not as selective as the T3-O33 position and why ferrierite, although it contains 8MR channels, is less selective than mordenite. The competing effect of water is explained at the molecular level, and the molecular microkinetic reaction model has been established.

  13. Characterizing Age-Related Positivity Effects in Situation Selection

    ERIC Educational Resources Information Center

    Sands, Molly; Livingstone, Kimberly M.; Isaacowitz, Derek M.

    2018-01-01

    Situation selection--choosing to enter or avoid situations based on how they will likely make you feel--is theorized to be a useful emotion regulation strategy, especially in older age. However, research on the use of situation selection for emotion regulation is limited, and the existing findings about age differences are mixed, with some studies…

  14. Attraction of position preference by spatial attention throughout human visual cortex.

    PubMed

    Klein, Barrie P; Harvey, Ben M; Dumoulin, Serge O

    2014-10-01

    Voluntary spatial attention concentrates neural resources at the attended location. Here, we examined the effects of spatial attention on spatial position selectivity in humans. We measured population receptive fields (pRFs) using high-field functional MRI (fMRI) (7T) while subjects performed an attention-demanding task at different locations. We show that spatial attention attracts pRF preferred positions across the entire visual field, not just at the attended location. This global change in pRF preferred positions systematically increases up the visual hierarchy. We model these pRF preferred position changes as an interaction between two components: an attention field and a pRF without the influence of attention. This computational model suggests that increasing effects of attention up the hierarchy result primarily from differences in pRF size and that the attention field is similar across the visual hierarchy. A similar attention field suggests that spatial attention transforms different neural response selectivities throughout the visual hierarchy in a similar manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family[W][OPEN

    PubMed Central

    Ren, Lin-Ling; Liu, Yan-Jing; Liu, Hai-Jing; Qian, Ting-Ting; Qi, Li-Wang; Wang, Xiao-Ru; Zeng, Qing-Yin

    2014-01-01

    Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families. PMID:24934172

  16. Mediator Effects of Positive Emotions on Social Support and Depression among Adolescents Suffering from Mobile Phone Addiction.

    PubMed

    Li, Menglong; Jiang, Xia; Ren, Yujia

    2017-06-01

    Depression is a common mental disorder that is widely seen among adolescents suffering from mobile phone addiction. While it is well known that both positive emtions in adolescents wiotions and social support can have a positive impact by helping individuals to maintain a positive attitude, the correlation between positive emotions, social support, and depression among these adolescents remains to be investigated. This study examined the mediator effects of positive emotions on the relationship between social support and depression among adolescents suffering from mobile phone addiction. For this study, conducted in 2016, we selected 1,346 adolescent students from three middle schools (ranging from Junior Grade One to Senior Grade Three) in Hunan Province of China, to participate in the survey. Participants were selected using the stratified cluster random sampling method, and all participants remained anonymous throughout the study. Each participant completed the Self-made General Situation Questionnaire, the Social Support Rating Scale, the Positive and Negative Affect Schedule, the Center for Epidemiological Studies Depression Scale, and the Mobile Phone Addiction Tendency Scale. There was significant positive correlation between positive emotions and social support. Both positive emotions and social support demonstrated significant negative correlation with depression. Positive emotions had partial mediator effects on the relationship between social support and depression (P<0.01). Both social support and positive emotions can lower levels of depression among adolescents suffering from mobile phone addiction. Social support contributes to positive emoth mobile phone addiction, thereby reducing their levels of depression. These findings suggest that more support and care should be given to this particular adolescent population.

  17. Parental effects and the evolution of phenotypic memory.

    PubMed

    Kuijper, B; Johnstone, R A

    2016-02-01

    Despite growing evidence for nongenetic inheritance, the ecological conditions that favour the evolution of heritable parental or grandparental effects remain poorly understood. Here, we systematically explore the evolution of parental effects in a patch-structured population with locally changing environments. When selection favours the production of a mix of offspring types, this mix differs according to the parental phenotype, implying that parental effects are favoured over selection for bet-hedging in which the mixture of offspring phenotypes produced does not depend on the parental phenotype. Positive parental effects (generating a positive correlation between parental and offspring phenotype) are favoured in relatively stable habitats and when different types of local environment are roughly equally abundant, and can give rise to long-term parental inheritance of phenotypes. By contrast, unstable habitats can favour negative parental effects (generating a negative correlation between parental and offspring phenotype), and under these circumstances, even slight asymmetries in the abundance of local environmental states select for marked asymmetries in transmission fidelity. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  18. Views of the self and others at different ages: utility of repertory grid technique in detecting the positivity effect in aging.

    PubMed

    Williams, Ben D; Harter, Stephanie Lewis

    2010-01-01

    Socioemotional selectivity theory (Carstensen, 1995) posits a "positivity effect" in older adults, describing an increasing tendency to attend to, process, interpret, and remember events and others in life in a positive fashion as one ages. Drawing on personal construct theory, Viney (1993) observes increasing integration of constructions of self with others across the lifespan. The current study extends assessment of the positivity effect, integrating it with personal construct theory, by use of Repertory Grid (RepGrid) analysis. Consistent with the positivity effect, older adults (ages 54-86) described others more positively on RepGrid measures in comparison to younger adults (ages 18-25). Older adults also described the self as more similar to others and tended to describe the self more positively. The age groups did not differ in measures of psychological distress or well being with the exception of older adults describing more autonomy.

  19. Signatures of co-evolutionary host-pathogen interactions in the genome of the entomopathogenic nematode Steinernema carpocapsae.

    PubMed

    Flores-Ponce, Mitzi; Vallebueno-Estrada, Miguel; González-Orozco, Eduardo; Ramos-Aboites, Hilda E; García-Chávez, J Noé; Simões, Nelson; Montiel, Rafael

    2017-04-26

    The entomopathogenic nematode Steinernema carpocapsae has been used worldwide as a biocontrol agent for insect pests, making it an interesting model for understanding parasite-host interactions. Two models propose that these interactions are co-evolutionary processes in such a way that equilibrium is never reached. In one model, known as "arms race", new alleles in relevant genes are fixed in both host and pathogens by directional positive selection, producing recurrent and alternating selective sweeps. In the other model, known as"trench warfare", persistent dynamic fluctuations in allele frequencies are sustained by balancing selection. There are some examples of genes evolving according to both models, however, it is not clear to what extent these interactions might alter genome-level evolutionary patterns and intraspecific diversity. Here we investigate some of these aspects by studying genomic variation in S. carpocapsae and other pathogenic and free-living nematodes from phylogenetic clades IV and V. To look for signatures of an arms-race dynamic, we conducted massive scans to detect directional positive selection in interspecific data. In free-living nematodes, we detected a significantly higher proportion of genes with sites under positive selection than in parasitic nematodes. However, in these genes, we found more enriched Gene Ontology terms in parasites. To detect possible effects of dynamic polymorphisms interactions we looked for signatures of balancing selection in intraspecific genomic data. The observed distribution of Tajima's D values in S. carpocapsae was more skewed to positive values and significantly different from the observed distribution in the free-living Caenorhabditis briggsae. Also, the proportion of significant positive values of Tajima's D was elevated in genes that were differentially expressed after induction with insect tissues as compared to both non-differentially expressed genes and the global scan. Our study provides a first portrait of the effects that lifestyle might have in shaping the patterns of selection at the genomic level. An arms-race between hosts and pathogens seems to be affecting specific genetic functions but not necessarily increasing the number of positively selected genes. Trench warfare dynamics seem to be acting more generally in the genome, likely focusing on genes responding to the interaction, rather than targeting specific genetic functions.

  20. Rethinking volitional control over task choice in multitask environments: use of a stimulus set selection strategy in voluntary task switching.

    PubMed

    Arrington, Catherine M; Weaver, Starla M

    2015-01-01

    Under conditions of volitional control in multitask environments, subjects may engage in a variety of strategies to guide task selection. The current research examines whether subjects may sometimes use a top-down control strategy of selecting a task-irrelevant stimulus dimension, such as location, to guide task selection. We term this approach a stimulus set selection strategy. Using a voluntary task switching procedure, subjects voluntarily switched between categorizing letter and number stimuli that appeared in two, four, or eight possible target locations. Effects of stimulus availability, manipulated by varying the stimulus onset asynchrony between the two target stimuli, and location repetition were analysed to assess the use of a stimulus set selection strategy. Considered across position condition, Experiment 1 showed effects of both stimulus availability and location repetition on task choice suggesting that only in the 2-position condition, where selection based on location always results in a target at the selected location, subjects may have been using a stimulus set selection strategy on some trials. Experiment 2 replicated and extended these findings in a visually more cluttered environment. These results indicate that, contrary to current models of task selection in voluntary task switching, the top-down control of task selection may occur in the absence of the formation of an intention to perform a particular task.

  1. Correlation and path coefficient analysis of quantitative characters in spine gourd (Momordica dioica Roxb.).

    PubMed

    Aliya, F; Begum, H; Reddy, M T; Sivaraj, N; Pandravada, S R; Narshimulu, G

    2014-05-01

    Fifty genotypes of spine gourd (Momordica dioica Roxb.) were evaluated in a randomized block design with two replications at the Vegetable Research Station, Rajendranagar, Hyderabad, Andhra Pradesh, India during kharif, 2012. Correlation and path coefficient analysis were carried out to study the character association and contribution, respectively for twelve quantitative characters namely vine length (m), number of stems per plant, days to first female flower appearance, first female flowering node, days to first fruit harvest, days to last fruit harvest, fruiting period (days), fruit length (cm), fruit width (cm), fruit weight (g), number of fruits per plant and fruit yield per plant (kg) for identification of the potential selection indices. Correlation and path coefficient analyses revealed that fruiting period and number of fruits per plant not only had positively significant correlation with fruit yield but also had positively high direct effect on it and are regarded as the main determinants of fruit yield. Days to first fruit harvest had positively moderate direct effect on fruit yield and its association was negatively significant, days to last fruit harvest had negatively high direct effect on fruit yield and its association was significant positively, hence restricted simultaneous selection can be made for days to first fruit harvest and days to last fruit harvest. The improvement in fruit yield can be effective if selection is based on days to first fruit harvest, days to last fruit harvest, fruiting period and number of fruits per plant.

  2. Money Changes Everything: Funding Shocks and Optimal Admissions and Financial Aid Policies in Higher Education

    ERIC Educational Resources Information Center

    Nagler, Matthew G.

    2006-01-01

    The paper examines the effect of a shock to university funding on tuition net of financial aid, admissions selectivity, and enrollment levels chosen by an optimizing university. Whereas a positive shock, such as a major donation, results in lower net tuition and greater selectivity with respect to all students, its effect on enrollment may not be…

  3. Effects of organizational citizenship behaviors on selection decisions in employment interviews.

    PubMed

    Podsakoff, Nathan P; Whiting, Steven W; Podsakoff, Philip M; Mishra, Paresh

    2011-03-01

    This article reports on an experiment examining the effects of job candidates' propensity to exhibit organizational citizenship behaviors (OCBs) on selection decisions made in the context of a job interview. We developed videos that manipulated candidate responses to interview questions tapping task performance and citizenship behavior content in 2 administrative positions. Results obtained from 480 undergraduates provided support for our hypotheses that job candidates who exhibited higher levels of helping, voice, and loyalty behaviors were generally rated as more competent, received higher overall evaluations, and received higher salary recommendations than job candidates who exhibited lower levels of these behaviors. These effects held even after taking into account candidate responses regarding task performance. We also found that candidate responses to OCB-related questions tended to have a greater effect on selection decisions for the higher level position (supervisor of administrative personnel) than for the lower level one (administrative assistant). Finally, content analyses of open-ended responses indicated that participants' selection decisions were particularly sensitive to candidates who exhibited low levels of voice and helping behaviors. Implications and future research are discussed. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  4. Alphabetical Order Effects in School Admissions

    ERIC Educational Resources Information Center

    Jurajda, Štepán; Münich, Daniel

    2016-01-01

    If school admission committees use alphabetically sorted lists of applicants in their evaluations, one's position in the alphabet according to last name initial may be important in determining access to selective schools. Jurajda and Münich (2010) "Admission to Selective Schools, Alphabetically". "Economics of Education…

  5. Expression Divergence Is Correlated with Sequence Evolution but Not Positive Selection in Conifers.

    PubMed

    Hodgins, Kathryn A; Yeaman, Sam; Nurkowski, Kristin A; Rieseberg, Loren H; Aitken, Sally N

    2016-06-01

    The evolutionary and genomic determinants of sequence evolution in conifers are poorly understood, and previous studies have found only limited evidence for positive selection. Using RNAseq data, we compared gene expression profiles to patterns of divergence and polymorphism in 44 seedlings of lodgepole pine (Pinus contorta) and 39 seedlings of interior spruce (Picea glauca × engelmannii) to elucidate the evolutionary forces that shape their genomes and their plastic responses to abiotic stress. We found that rapidly diverging genes tend to have greater expression divergence, lower expression levels, reduced levels of synonymous site diversity, and longer proteins than slowly diverging genes. Similar patterns were identified for the untranslated regions, but with some exceptions. We found evidence that genes with low expression levels had a larger fraction of nearly neutral sites, suggesting a primary role for negative selection in determining the association between evolutionary rate and expression level. There was limited evidence for differences in the rate of positive selection among genes with divergent versus conserved expression profiles and some evidence supporting relaxed selection in genes diverging in expression between the species. Finally, we identified a small number of genes that showed evidence of site-specific positive selection using divergence data alone. However, estimates of the proportion of sites fixed by positive selection (α) were in the range of other plant species with large effective population sizes suggesting relatively high rates of adaptive divergence among conifers. © 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.

  6. Positive Changes in Perceptions and Selections of Healthful Foods by College Students after a Short-Term Point-of-Selection Intervention at a Dining Hall

    ERIC Educational Resources Information Center

    Peterson, Sharon; Duncan, Diana Poovey; Null, Dawn Bloyd; Roth, Sara Long; Gill, Lynn

    2010-01-01

    Objective: Determine the effects of a short-term, multi-faceted, point-of-selection intervention on college students' perceptions and selection of 10 targeted healthful foods in a university dining hall and changes in their self-reported overall eating behaviors. Participants: 104 college students, (age 18-23) completed pre-I and post-I surveys.…

  7. The Effects of College Students' Positive Thinking, Learning Motivation and Self-Regulation through a Self-Reflection Intervention in Taiwan

    ERIC Educational Resources Information Center

    Wang, Hsin-Hui; Chen, Hsiang-Ting; Lin, Huann-Shyang; Hong, Zuway-R

    2017-01-01

    This quasi-experimental study examined the effects of a self-reflection intervention on college (college in this article refers to university-level education) students' positive thinking, learning motivation and self-regulation in Taiwan. One hundred and two college students were selected to participate in an 18-week intervention forming the…

  8. Effect of Items Direction (Positive or Negative) on the Factorial Construction and Criterion Related Validity in Likert Scale

    ERIC Educational Resources Information Center

    Naji Qasem, Mamun Ali; Ahmad Gul, Showkeen Bilal

    2014-01-01

    The study was conducted to know the effect of items direction (positive or negative) on the factorial construction and criterion related validity in Likert scale. The descriptive survey research method was used for the study and the sample consisted of 510 undergraduate students selected by used random sampling technique. A scale developed by…

  9. Effect of Items Direction (Positive or Negative) on the Reliability in Likert Scale. Paper-11

    ERIC Educational Resources Information Center

    Gul, Showkeen Bilal Ahmad; Qasem, Mamun Ali Naji; Bhat, Mehraj Ahmad

    2015-01-01

    In this paper an attempt was made to analyze the effect of items direction (positive or negative) on the Alpha Cronbach reliability coefficient and the Split Half reliability coefficient in Likert scale. The descriptive survey research method was used for the study and sample of 510 undergraduate students were selected by used random sampling…

  10. Situation Selection and Modification for Emotion Regulation in Younger and Older Adults.

    PubMed

    Livingstone, Kimberly M; Isaacowitz, Derek M

    2015-11-01

    This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or "just view" condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation.

  11. Improving the quality of the NHS workforce through values and competency-based selection.

    PubMed

    McGuire, Clare; Rankin, Jean; Matthews, Lynsay; Cerinus, Marie; Zaveri, Swati

    2016-07-01

    Robust selection processes are essential to ensure the best and most appropriate candidates for nursing, midwifery and allied health professional (NMAHP) positions are appointed, and subsequently enhance patient care. This article reports on a study that explored interviewers' and interviewees' experiences of using values and competency-based interview (VCBI) methods for NMAHPs. Results suggest that this resource could have a positive effect on the quality of the NMAHP workforce, and therefore on patient care. This method of selection could be used in other practice areas in health care, and refinement of the resource should focus on supporting interview panels to develop their VCBI skills and experience.

  12. Applicant Appearance and Selection Decision Making: Revitalizing Employment Interview Education.

    ERIC Educational Resources Information Center

    Ilkka, Richard J.

    1995-01-01

    Presents five instructional propositions based on employment interview research on the relationship between applicant appearance and interviewer selection decisions. Argues that educators should examine the process of appearance attribution, explore appearance and position expectations, invite dialog of alleged effects, and assess related…

  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. Permeability-Selectivity Analysis of Microfiltration and Ultrafiltration Membranes: Effect of Pore Size and Shape Distribution and Membrane Stretching.

    PubMed

    Siddiqui, Muhammad Usama; Arif, Abul Fazal Muhammad; Bashmal, Salem

    2016-08-06

    We present a modeling approach to determine the permeability-selectivity tradeoff for microfiltration and ultrafiltration membranes with a distribution of pore sizes and pore shapes. Using the formulated permeability-selectivity model, the effect of pore aspect ratio and pore size distribution on the permeability-selectivity tradeoff of the membrane is analyzed. A finite element model is developed to study the effect of membrane stretching on the distribution of pore sizes and shapes in the stretched membrane. The effect of membrane stretching on the permeability-selectivity tradeoff of membranes is also analyzed. The results show that increasing pore aspect ratio improves membrane performance while increasing the width of pore size distribution deteriorates the performance. It was also found that the effect of membrane stretching on the permeability-selectivity tradeoff is greatly affected by the uniformity of pore distribution in the membrane. Stretching showed a positive shift in the permeability-selectivity tradeoff curve of membranes with well-dispersed pores while in the case of pore clustering, a negative shift in the permeability-selectivity tradeoff curve was observed.

  15. Take a look at the bright side: Effects of positive body exposure on selective visual attention in women with high body dissatisfaction.

    PubMed

    Glashouwer, Klaske A; Jonker, Nienke C; Thomassen, Karen; de Jong, Peter J

    2016-08-01

    Women with high body dissatisfaction look less at their 'beautiful' body parts than their 'ugly' body parts. This study tested the robustness of this selective viewing pattern and examined the influence of positive body exposure on body-dissatisfied women's attention for 'ugly' and 'beautiful' body parts. In women with high body dissatisfaction (N = 28) and women with low body dissatisfaction (N = 14) eye-tracking was used to assess visual attention towards pictures of their own and other women's bodies. Participants with high body dissatisfaction were randomly assigned to 5 weeks positive body exposure (n = 15) or a no-treatment condition (n = 13). Attention bias was assessed again after 5 weeks. Body-dissatisfied women looked longer at 'ugly' than 'beautiful' body parts of themselves and others, while participants with low body dissatisfaction attended equally long to own/others' 'beautiful' and 'ugly' body parts. Although positive body exposure was very effective in improving participants' body satisfaction, it did not systematically change participants' viewing pattern. The tendency to preferentially allocate attention towards one's 'ugly' body parts seems a robust phenomenon in women with body dissatisfaction. Yet, modifying this selective viewing pattern seems not a prerequisite for successfully improving body satisfaction via positive body exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Memory for faces with emotional expressions in Alzheimer's disease and healthy older participants: positivity effect is not only due to familiarity.

    PubMed

    Sava, Alina-Alexandra; Krolak-Salmon, Pierre; Delphin-Combe, Floriane; Cloarec, Morgane; Chainay, Hanna

    2017-01-01

    Young individuals better memorize initially seen faces with emotional rather than neutral expressions. Healthy older participants and Alzheimer's disease (AD) patients show better memory for faces with positive expressions. The socioemotional selectivity theory postulates that this positivity effect in memory reflects a general age-related preference for positive stimuli, subserving emotion regulation. Another explanation might be that older participants use compensatory strategies, often considering happy faces as previously seen. The question about the existence of this effect in tasks not permitting such compensatory strategies is still open. Thus, we compared the performance of healthy participants and AD patients for positive, neutral, and negative faces in such tasks. Healthy older participants and AD patients showed a positivity effect in memory, but there was no difference between emotional and neutral faces in young participants. Our results suggest that the positivity effect in memory is not entirely due to the sense of familiarity for smiling faces.

  17. 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.

  18. Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure.

    PubMed

    Panthee, Nirmal; Okada, Jun-ichi; Washio, Takumi; Mochizuki, Youhei; Suzuki, Ryohei; Koyama, Hidekazu; Ono, Minoru; Hisada, Toshiaki; Sugiura, Seiryo

    2016-07-01

    Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P<0.01) or the maximum value of the derivative of left ventricular pressure (P<0.01). The optimal lead positions produced better outcomes compared with the worst positioning in all dogs studied, although there were significant variations in responses. Variations in ventricular wall thickness among the dogs may have contributed to these responses. Thus CRT simulations using the individualized three-dimensional heart models can predict acute hemodynamic improvement, and help determine the optimal positions of the pacing lead. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Cloning, expression of, and evidence of positive selection for, the prolactin receptor gene in Chinese giant salamander (Andrias davidianus).

    PubMed

    Hu, Qiaomu; Meng, Yan; Tian, Haifeng; Chen, Songlin; Xiao, Hanbing

    2015-12-01

    Prolactin receptor (PRLR) is a protein associated with reproduction in mammals and with osmoregulation in fish. In this study, the complete length of Chinese giant salamander Andrias davidianus prolactin receptor (AD-prlr) was cloned. Andrias davidianus prlr expression was high in the kidney, pituitary, and ovary and low in other examined tissues. The AD-prlr levels were higher in ovary than in testis, and increased in ovaries with age from 1 to 6 years. To determine effect of exogenous androgen and aromatase inhibitor on AD-prlr expression, methyltestosterone (MT) and letrozole (LE) were injected, resulting in decreased AD-prlr in both brain and ovary, with MT repressing prlr transcription more rapidly than did LE. The molecular evolution of prlr was assessed, and found to have undergone a complex evolution process. The obranch-site test detected four positively selected sites in ancestral lineages prior to the separation of mammals and birds. Fourteen sites underwent positive selection in ancestral lineages of birds and six were positively selected in amphibians. The site model showed that 16, 7, and 30 sites underwent positive selection in extant mammals, amphibians, and birds, respectively. The positively selected sites in amphibians were located outside the transmembrane domain, with four in the extracellular and three in the intracellular domain, indicating that the transmembrane region might be conserved and essential for protein function. Our findings provide a basis for further studies of AD-prlr function and molecular evolution in Chinese giant salamander. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 707-719, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Neural Codes for One's Own Position and Direction in a Real-World "Vista" Environment.

    PubMed

    Sulpizio, Valentina; Boccia, Maddalena; Guariglia, Cecilia; Galati, Gaspare

    2018-01-01

    Humans, like animals, rely on an accurate knowledge of one's spatial position and facing direction to keep orientated in the surrounding space. Although previous neuroimaging studies demonstrated that scene-selective regions (the parahippocampal place area or PPA, the occipital place area or OPA and the retrosplenial complex or RSC), and the hippocampus (HC) are implicated in coding position and facing direction within small-(room-sized) and large-scale navigational environments, little is known about how these regions represent these spatial quantities in a large open-field environment. Here, we used functional magnetic resonance imaging (fMRI) in humans to explore the neural codes of these navigationally-relevant information while participants viewed images which varied for position and facing direction within a familiar, real-world circular square. We observed neural adaptation for repeated directions in the HC, even if no navigational task was required. Further, we found that the amount of knowledge of the environment interacts with the PPA selectivity in encoding positions: individuals who needed more time to memorize positions in the square during a preliminary training task showed less neural attenuation in this scene-selective region. We also observed adaptation effects, which reflect the real distances between consecutive positions, in scene-selective regions but not in the HC. When examining the multi-voxel patterns of activity we observed that scene-responsive regions and the HC encoded both spatial information and that the RSC classification accuracy for positions was higher in individuals scoring higher to a self-reported questionnaire of spatial abilities. Our findings provide new insight into how the human brain represents a real, large-scale "vista" space, demonstrating the presence of neural codes for position and direction in both scene-selective and hippocampal regions, and revealing the existence, in the former regions, of a map-like spatial representation reflecting real-world distance between consecutive positions.

  1. 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.

  2. Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.

    PubMed

    Tuplin, Erin W; Holahan, Matthew R

    2017-11-14

    The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes. To identify evidence in the literature that elucidates the pharmacological profile of aripiprazole.s. We searched PubMed for peer reviewed articles on aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects in animal models of schizophrenia symptoms. Aripiprazole is a newer atypical antipsychotic that displays a unique pharmacological profile, including partial D2 agonism and functionally selective properties. Aripiprazole is effective at treating the positive symptoms of schizophrenia and has the potential to treat negative and cognitive symptoms at least as well as other atypical antipsychotics. The drug has a favorable side-effect profile and has a low propensity to result in EPS or metabolic syndromes. Animal models of schizophrenia have been used to determine the efficacy of aripiprazole in symptom management. In these instances, aripiprazole resulted in the reversal of deficits in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole requires a greater than 90% occupancy rate at D2 receptors to be clinically active and does not produce EPS, this suggests a functionally selective effect on intracellular signaling pathways. A combination of factors such as dopamine system stabilization via partial agonism, functional selectivity at D2 receptors, and serotonin-dopamine system interaction may contribute to the ability of aripiprazole to successfully manage schizophrenia symptoms. This review examines these mechanisms of action to further clarify the pharmacological actions of aripiprazole. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Selection, Training, and Manpower Recruitment in Rehabilitation.

    ERIC Educational Resources Information Center

    Shapiro, Jeffrey G.

    The critical shortage of trained personnel for rehabilitation work can be alleviated by careful selection of non-professionals to fill the existing positions. Research suggests that certain personal characteristics of counselors contribute substantially to the effectiveness of changing the behavior of clients. Traits of genuineness, empathy and…

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

    Blume-Kohout, Robin J; Scholten, Travis L.

    Quantum state tomography on a d-dimensional system demands resources that grow rapidly with d. They may be reduced by using model selection to tailor the number of parameters in the model (i.e., the size of the density matrix). Most model selection methods typically rely on a test statistic and a null theory that describes its behavior when two models are equally good. Here, we consider the loglikelihood ratio. Because of the positivity constraint ρ ≥ 0, quantum state space does not generally satisfy local asymptotic normality (LAN), meaning the classical null theory for the loglikelihood ratio (the Wilks theorem) shouldmore » not be used. Thus, understanding and quantifying how positivity affects the null behavior of this test statistic is necessary for its use in model selection for state tomography. We define a new generalization of LAN, metric-projected LAN, show that quantum state space satisfies it, and derive a replacement for the Wilks theorem. In addition to enabling reliable model selection, our results shed more light on the qualitative effects of the positivity constraint on state tomography.« less

  5. Fragrance allergy in patients with hand eczema - a clinical study.

    PubMed

    Heydorn, Siri; Johansen, Jeanne Duus; Andersen, Klaus E; Bruze, Magnus; Svedman, Cecilia; White, Ian R; Basketter, David A; Menné, Torkil

    2003-06-01

    Fragrance allergy and hand eczema are both common among dermatological patients. Fragrance mix (FM) and its constituents have a recognized relevance to exposure to fine fragrances and cosmetic products. Based on extensive chemical analysis and database search, a new selection of fragrances was established, including 14 known fragrance allergens present in products to which hand exposure would occur. A non-irritating patch-test concentration for some fragrances was established in 212 consecutive patients. 658 consecutive patients presenting with hand eczema were patch tested with the European standard series and the developed selection of fragrances. 67 (10.2%) of the 658 patients had a positive reaction to 1 or more of our selection of fragrance chemicals present in the new selection. The most common reactions to fragrances not included in the FM were to citral, Lyral (hydroxyisohexyl-3-cyclohexene carboxaldehyde) and oxidized l-limonene. A concomitant reaction to the FM identified potential fragrance allergy in less than (1/2) of these patients. Exposure assessment and a statistically significant association between a positive patch test to our selected fragrances and patients' history support the relevance of this selection of fragrances. Those with a positive reaction to our selected fragrances were significantly more likely to have 1 or more positive patch tests in the standard series. This observation is the basis for the hypothesis concerning cross-reactivity and the effect of simultaneous exposure. The study found that fragrance allergy could be a common problem in patients with eczema on the hands.

  6. The effect of parasites on sex differences in selection.

    PubMed

    Sharp, N P; Vincent, C M

    2015-04-01

    The life history strategies of males and females are often divergent, creating the potential for sex differences in selection. Deleterious mutations may be subject to stronger selection in males, owing to sexual selection, which can improve the mean fitness of females and reduce mutation load in sexual populations. However, sex differences in selection might also maintain sexually antagonistic genetic variation, creating a sexual conflict load. The overall impact of separate sexes on fitness is unclear, but the net effect is likely to be positive when there is a large sex difference in selection against deleterious mutations. Parasites can also have sex-specific effects on fitness, and there is evidence that parasites can intensify the fitness consequences of deleterious mutations. Using lines that accumulated mutations for over 60 generations, we studied the effect of the pathogenic bacterium Pseudomonas aeruginosa on sex differences in selection in the fruit fly Drosophila melanogaster. Pseudomonas infection increased the sex difference in selection, but may also have weakened the intersexual correlation for fitness. Our results suggest that parasites may increase the benefits of sexual selection.

  7. Mediators of effects of a selective family-focused violence prevention approach for middle school students.

    PubMed

    2012-02-01

    This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N = 1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student's valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth.

  8. RELAX: detecting relaxed selection in a phylogenetic framework.

    PubMed

    Wertheim, Joel O; Murrell, Ben; Smith, Martin D; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2015-03-01

    Relaxation of selective strength, manifested as a reduction in the efficiency or intensity of natural selection, can drive evolutionary innovation and presage lineage extinction or loss of function. Mechanisms through which selection can be relaxed range from the removal of an existing selective constraint to a reduction in effective population size. Standard methods for estimating the strength and extent of purifying or positive selection from molecular sequence data are not suitable for detecting relaxed selection, because they lack power and can mistake an increase in the intensity of positive selection for relaxation of both purifying and positive selection. Here, we present a general hypothesis testing framework (RELAX) for detecting relaxed selection in a codon-based phylogenetic framework. Given two subsets of branches in a phylogeny, RELAX can determine whether selective strength was relaxed or intensified in one of these subsets relative to the other. We establish the validity of our test via simulations and show that it can distinguish between increased positive selection and a relaxation of selective strength. We also demonstrate the power of RELAX in a variety of biological scenarios where relaxation of selection has been hypothesized or demonstrated previously. We find that obligate and facultative γ-proteobacteria endosymbionts of insects are under relaxed selection compared with their free-living relatives and obligate endosymbionts are under relaxed selection compared with facultative endosymbionts. Selective strength is also relaxed in asexual Daphnia pulex lineages, compared with sexual lineages. Endogenous, nonfunctional, bornavirus-like elements are found to be under relaxed selection compared with exogenous Borna viruses. Finally, selection on the short-wavelength sensitive, SWS1, opsin genes in echolocating and nonecholocating bats is relaxed only in lineages in which this gene underwent pseudogenization; however, selection on the functional medium/long-wavelength sensitive opsin, M/LWS1, is found to be relaxed in all echolocating bats compared with nonecholocating bats. © The Author 2014. 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.

  9. The effect of prenatal care on birthweight: a full-information maximum likelihood approach.

    PubMed

    Rous, Jeffrey J; Jewell, R Todd; Brown, Robert W

    2004-03-01

    This paper uses a full-information maximum likelihood estimation procedure, the Discrete Factor Method, to estimate the relationship between birthweight and prenatal care. This technique controls for the potential biases surrounding both the sample selection of the pregnancy-resolution decision and the endogeneity of prenatal care. In addition, we use the actual number of prenatal care visits; other studies have normally measured prenatal care as the month care is initiated. We estimate a birthweight production function using 1993 data from the US state of Texas. The results underscore the importance of correcting for estimation problems. Specifically, a model that does not control for sample selection and endogeneity overestimates the benefit of an additional visit for women who have relatively few visits. This overestimation may indicate 'positive fetal selection,' i.e., women who did not abort may have healthier babies. Also, a model that does not control for self-selection and endogenity predicts that past 17 visits, an additional visit leads to lower birthweight, while a model that corrects for these estimation problems predicts a positive effect for additional visits. This result shows the effect of mothers with less healthy fetuses making more prenatal care visits, known as 'adverse selection' in prenatal care. Copyright 2003 John Wiley & Sons, Ltd.

  10. Activity in human visual and parietal cortex reveals object-based attention in working memory.

    PubMed

    Peters, Benjamin; Kaiser, Jochen; Rahm, Benjamin; Bledowski, Christoph

    2015-02-25

    Visual attention enables observers to select behaviorally relevant information based on spatial locations, features, or objects. Attentional selection is not limited to physically present visual information, but can also operate on internal representations maintained in working memory (WM) in service of higher-order cognition. However, only little is known about whether attention to WM contents follows the same principles as attention to sensory stimuli. To address this question, we investigated in humans whether the typically observed effects of object-based attention in perception are also evident for object-based attentional selection of internal object representations in WM. In full accordance with effects in visual perception, the key behavioral and neuronal characteristics of object-based attention were observed in WM. Specifically, we found that reaction times were shorter when shifting attention to memory positions located on the currently attended object compared with equidistant positions on a different object. Furthermore, functional magnetic resonance imaging and multivariate pattern analysis of visuotopic activity in visual (areas V1-V4) and parietal cortex revealed that directing attention to one position of an object held in WM also enhanced brain activation for other positions on the same object, suggesting that attentional selection in WM activates the entire object. This study demonstrated that all characteristic features of object-based attention are present in WM and thus follows the same principles as in perception. Copyright © 2015 the authors 0270-6474/15/353360-10$15.00/0.

  11. Role Appropriateness of Educational Fields: Bias in Selection.

    ERIC Educational Resources Information Center

    Smith, Elizabeth P.; And Others

    Bias towards women exists in the selection of applicants to professional and other positions. This research investigated the effects of two rater variables--sex and attitude toward women--and three applicant variables--sex, field (engineering-dietetics), and attributes--(feminine-masculine) upon ratings of competency and personal charm. Analyses…

  12. 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.

  13. Long-term sickness absence during pregnancy and the gender balance of workplaces.

    PubMed

    Melsom, Anne M

    2014-11-01

    This study addresses how the gender composition of workplaces affects pregnant women's sickness absence. It also assesses whether an observed association may be explaine by differential selection to female- or male-dominated workplaces. The analyses are based on Norwegian registry data from 2003-2011. Using Poisson regressions with detailed control for occupational categories, I examine whether the number of absence days are associated with the proportion of females at the workplace. I address possible selection effects by Poisson regressions with fixed individual effects using only within-individual variation on women with two or more pregnancies during the time window. The analyses indicate a positive and significant relationship between the female proportion in workplaces and sickness absence rates during pregnancy. Analyses limited to within-individual variation also show positive and significant effects of similar strength, indicating that the observed relationship is not due to differential selection of absence-prone pregnant workers to female-dominated workplaces. The proportion of female individuals at workplaces is positively associated with sickness absence rates during pregnancy this association is not likely explained by occupational nor individual characteristics the results are consistent with absence culture theory and more lenient norms concerning sickness absence during pregnancy at female-dominated workplaces. © 2014 the Nordic Societies of Public Health.

  14. Genetic selection for a highly functional cysteine-less membrane protein using site-saturation mutagenesis

    PubMed Central

    Arendt, Cassandra S.; Ri, Keirei; Yates, Phillip A.; Ullman, Buddy

    2007-01-01

    We describe an efficient method for generating highly functional membrane proteins with variant amino acids at defined positions that couples a modified site-saturation strategy with functional genetic selection. We applied this method to the production of a cysteine-less variant of the Crithidia fasciculata inosine-guanosine permease CfNT2, in order to facilitate biochemical studies using thiol-specific modifying reagents. Of ten endogenous cysteine residues in CfNT2, two cannot be replaced with serine or alanine without loss of function. High-quality single- and double-mutant libraries were produced by combining a previously reported site-saturation mutagenesis scheme based on the Quikchange method with a novel gel purification step that effectively eliminated template DNA from the products. Following selection for functional complementation in S. cerevisiae cells auxotrophic for purines, several highly functional non-cysteine substitutions were efficiently identified at each desired position, allowing the construction of cysteine-less variants of CfNT2 that retained wild-type affinity for inosine. This combination of an improved site-saturation mutagenesis technique and positive genetic selection provides a simple and efficient means to identify functional and perhaps unexpected amino acid variants at a desired position. PMID:17481563

  15. Peptide selectivity between the PDZ domains of human pregnancy-related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes.

    PubMed

    Sun, Mei-Ling; Sun, Li-Mei; Wang, Yong-Qing

    2018-06-01

    The human HtrA family of serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) are the key enzymes associated with pregnancy and closely related to the development and progression of many pathological events. Previously, it was found that halogen substitution at the indole moiety of peptide Trp-1 residue can form a geometrically satisfactory halogen bond with the Drosophila discs large, zona occludens-1 (PDZ) domain of HtrA proteases. Here, we attempt to systematically investigate the effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains. The complex structures, interaction energies, halogen-bonding strength, and binding affinity of domain-peptide systems were modeled, analyzed, and measured via computational modeling and fluorescence-based assay. It is revealed that there is a compromise between the local rearrangement of halogen bond involving different halogen atoms and the global optimization of domain-peptide interaction; the substitution position is fundamentally important for peptide-binding affinity, while the halogen type can effectively shift peptide selectivity between the 4 domains. The HtrA1-PDZ and HtrA4-PDZ as well as HtrA2-PDZ and HtrA3-PDZ respond similarly to different halogen substitutions of peptide; -Br substitution at R2-position and -I substitution at R4-position are most effective in improving peptide selectivity for HtrA1-PDZ/HtrA4-PDZ and HtrA2-PDZ/HtrA3-PDZ, respectively; -F substitution would not address substantial effect on peptide selectivity for all the 4 domains. Consequently, the binding affinities of a native peptide ligand DSRIWWV -COOH as well as its 4 R2-halogenated counterparts were determined as 1.9, 1.4, 0.5, 0.27, and 0.92 μM, which are basically consistent with computational analysis. This study would help to rationally design selective peptide inhibitors of HtrA family members by using different halogen substitutions. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Inference of Evolutionary Forces Acting on Human Biological Pathways

    PubMed Central

    Daub, Josephine T.; Dupanloup, Isabelle; Robinson-Rechavi, Marc; Excoffier, Laurent

    2015-01-01

    Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures. PMID:25971280

  17. Polygenic variation maintained by balancing selection: pleiotropy, sex-dependent allelic effects and G x E interactions.

    PubMed Central

    Turelli, Michael; Barton, N H

    2004-01-01

    We investigate three alternative selection-based scenarios proposed to maintain polygenic variation: pleiotropic balancing selection, G x E interactions (with spatial or temporal variation in allelic effects), and sex-dependent allelic effects. Each analysis assumes an additive polygenic trait with n diallelic loci under stabilizing selection. We allow loci to have different effects and consider equilibria at which the population mean departs from the stabilizing-selection optimum. Under weak selection, each model produces essentially identical, approximate allele-frequency dynamics. Variation is maintained under pleiotropic balancing selection only at loci for which the strength of balancing selection exceeds the effective strength of stabilizing selection. In addition, for all models, polymorphism requires that the population mean be close enough to the optimum that directional selection does not overwhelm balancing selection. This balance allows many simultaneously stable equilibria, and we explore their properties numerically. Both spatial and temporal G x E can maintain variation at loci for which the coefficient of variation (across environments) of the effect of a substitution exceeds a critical value greater than one. The critical value depends on the correlation between substitution effects at different loci. For large positive correlations (e.g., rho(ij)2>3/4), even extreme fluctuations in allelic effects cannot maintain variation. Surprisingly, this constraint on correlations implies that sex-dependent allelic effects cannot maintain polygenic variation. We present numerical results that support our analytical approximations and discuss our results in connection to relevant data and alternative variance-maintaining mechanisms. PMID:15020487

  18. Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

    PubMed

    Robinson, Reeder; Franceschini, Stefano; Fedkenheuer, Michael; Rodriguez, Pedro J; Ellerbrock, Jacob; Romero, Elvira; Echandi, Maria Paulina; Martin Del Campo, Julia S; Sobrado, Pablo

    2014-04-01

    Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the KD values, as no major changes on the kcat or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP⁺ in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy.

    PubMed

    Byars, Sean G; Huang, Qin Qin; Gray, Lesley-Ann; Bakshi, Andrew; Ripatti, Samuli; Abraham, Gad; Stearns, Stephen C; Inouye, Michael

    2017-06-01

    Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

  20. Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs

    PubMed Central

    Freedman, Adam H.; Schweizer, Rena M.; Ortega-Del Vecchyo, Diego; Han, Eunjung; Davis, Brian W.; Gronau, Ilan; Silva, Pedro M.; Galaverni, Marco; Fan, Zhenxin; Marx, Peter; Lorente-Galdos, Belen; Ramirez, Oscar; Hormozdiari, Farhad; Alkan, Can; Vilà, Carles; Squire, Kevin; Geffen, Eli; Kusak, Josip; Boyko, Adam R.; Parker, Heidi G.; Lee, Clarence; Tadigotla, Vasisht; Siepel, Adam; Bustamante, Carlos D.; Harkins, Timothy T.; Nelson, Stanley F.; Marques-Bonet, Tomas; Ostrander, Elaine A.; Wayne, Robert K.; Novembre, John

    2016-01-01

    Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. PMID:26943675

  1. Use of data mining techniques to classify soil CO2 emission induced by crop management in sugarcane field.

    PubMed

    Farhate, Camila Viana Vieira; Souza, Zigomar Menezes de; Oliveira, Stanley Robson de Medeiros; Tavares, Rose Luiza Moraes; Carvalho, João Luís Nunes

    2018-01-01

    Soil CO2 emissions are regarded as one of the largest flows of the global carbon cycle and small changes in their magnitude can have a large effect on the CO2 concentration in the atmosphere. Thus, a better understanding of this attribute would enable the identification of promoters and the development of strategies to mitigate the risks of climate change. Therefore, our study aimed at using data mining techniques to predict the soil CO2 emission induced by crop management in sugarcane areas in Brazil. To do so, we used different variable selection methods (correlation, chi-square, wrapper) and classification (Decision tree, Bayesian models, neural networks, support vector machine, bagging with logistic regression), and finally we tested the efficiency of different approaches through the Receiver Operating Characteristic (ROC) curve. The original dataset consisted of 19 variables (18 independent variables and one dependent (or response) variable). The association between cover crop and minimum tillage are effective strategies to promote the mitigation of soil CO2 emissions, in which the average CO2 emissions are 63 kg ha-1 day-1. The variables soil moisture, soil temperature (Ts), rainfall, pH, and organic carbon were most frequently selected for soil CO2 emission classification using different methods for attribute selection. According to the results of the ROC curve, the best approaches for soil CO2 emission classification were the following: (I)-the Multilayer Perceptron classifier with attribute selection through the wrapper method, that presented rate of false positive of 13,50%, true positive of 94,20% area under the curve (AUC) of 89,90% (II)-the Bagging classifier with logistic regression with attribute selection through the Chi-square method, that presented rate of false positive of 13,50%, true positive of 94,20% AUC of 89,90%. However, the (I) approach stands out in relation to (II) for its higher positive class accuracy (high CO2 emission) and lower computational cost.

  2. Use of data mining techniques to classify soil CO2 emission induced by crop management in sugarcane field

    PubMed Central

    de Souza, Zigomar Menezes; Oliveira, Stanley Robson de Medeiros; Tavares, Rose Luiza Moraes; Carvalho, João Luís Nunes

    2018-01-01

    Soil CO2 emissions are regarded as one of the largest flows of the global carbon cycle and small changes in their magnitude can have a large effect on the CO2 concentration in the atmosphere. Thus, a better understanding of this attribute would enable the identification of promoters and the development of strategies to mitigate the risks of climate change. Therefore, our study aimed at using data mining techniques to predict the soil CO2 emission induced by crop management in sugarcane areas in Brazil. To do so, we used different variable selection methods (correlation, chi-square, wrapper) and classification (Decision tree, Bayesian models, neural networks, support vector machine, bagging with logistic regression), and finally we tested the efficiency of different approaches through the Receiver Operating Characteristic (ROC) curve. The original dataset consisted of 19 variables (18 independent variables and one dependent (or response) variable). The association between cover crop and minimum tillage are effective strategies to promote the mitigation of soil CO2 emissions, in which the average CO2 emissions are 63 kg ha-1 day-1. The variables soil moisture, soil temperature (Ts), rainfall, pH, and organic carbon were most frequently selected for soil CO2 emission classification using different methods for attribute selection. According to the results of the ROC curve, the best approaches for soil CO2 emission classification were the following: (I)–the Multilayer Perceptron classifier with attribute selection through the wrapper method, that presented rate of false positive of 13,50%, true positive of 94,20% area under the curve (AUC) of 89,90% (II)–the Bagging classifier with logistic regression with attribute selection through the Chi-square method, that presented rate of false positive of 13,50%, true positive of 94,20% AUC of 89,90%. However, the (I) approach stands out in relation to (II) for its higher positive class accuracy (high CO2 emission) and lower computational cost. PMID:29513765

  3. Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells

    NASA Astrophysics Data System (ADS)

    Aires, Antonio; Ocampo, Sandra M.; Simões, Bruno M.; Josefa Rodríguez, María; Cadenas, Jael F.; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B.; Carrascosa, José L.; Cortajarena, Aitziber L.

    2016-02-01

    Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.

  4. 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.

  5. SOC Strategies and Organizational Citizenship Behaviors toward the Benefits of Co-workers: A Multi-Source Study.

    PubMed

    Müller, Andreas; Weigl, Matthias

    2017-01-01

    Background: Individuals' behavioral strategies like selection, optimization, and compensation (SOC) contribute to efficient use of available resources. In the work context, previous studies revealed positive associations between employees' SOC use and favorable individual outcomes, like engagement and job performance. However, the social implications of self-directed behaviors like SOC that are favorable for the employee but may imply consequences for coworkers have not been investigated yet in an interpersonal work context. Objective: This study aimed to assess associations between employees' use of SOC behaviors at work and their organizational citizenship behaviors (OCB) toward the benefits of co-workers rated by their peers at work. We further sought to identify age-specific associations between SOC use and OCB. Design and Method: A cross-sectional design combining multi-source data was applied in primary school teachers (age range: 23-58 years) who frequently teach in dyads. N = 114 dyads were finally included. Teachers reported on their SOC strategies at work. Their peer colleagues evaluated teachers' OCB. Control variables were gender, workload, working hours, and perceived proximity of relationship between the dyads. Results: We observed a positive effect of loss-based selection behaviors on peer-rated OCB. Moreover, there was a significant two-way interaction effect between the use of compensation strategies and age on OCB, such that there was a positive association for older employees and a negative association for younger employees. There were no significant main and age-related interaction effects of elective selection, optimization, and of overall SOC strategies on OCB. Conclusion: Our study suggests that high use of loss-based selection and high use of compensation strategies in older employees is positively related with OCB as perceived by their colleagues. However, high use of compensation strategies in younger employees is perceived negatively related with OCB. Our findings contribute to a better understanding of the age-differentiated interpersonal effects of successful aging strategies in terms of SOC in organizations.

  6. SOC Strategies and Organizational Citizenship Behaviors toward the Benefits of Co-workers: A Multi-Source Study

    PubMed Central

    Müller, Andreas; Weigl, Matthias

    2017-01-01

    Background: Individuals’ behavioral strategies like selection, optimization, and compensation (SOC) contribute to efficient use of available resources. In the work context, previous studies revealed positive associations between employees’ SOC use and favorable individual outcomes, like engagement and job performance. However, the social implications of self-directed behaviors like SOC that are favorable for the employee but may imply consequences for coworkers have not been investigated yet in an interpersonal work context. Objective: This study aimed to assess associations between employees’ use of SOC behaviors at work and their organizational citizenship behaviors (OCB) toward the benefits of co-workers rated by their peers at work. We further sought to identify age-specific associations between SOC use and OCB. Design and Method: A cross-sectional design combining multi-source data was applied in primary school teachers (age range: 23–58 years) who frequently teach in dyads. N = 114 dyads were finally included. Teachers reported on their SOC strategies at work. Their peer colleagues evaluated teachers’ OCB. Control variables were gender, workload, working hours, and perceived proximity of relationship between the dyads. Results: We observed a positive effect of loss-based selection behaviors on peer-rated OCB. Moreover, there was a significant two-way interaction effect between the use of compensation strategies and age on OCB, such that there was a positive association for older employees and a negative association for younger employees. There were no significant main and age-related interaction effects of elective selection, optimization, and of overall SOC strategies on OCB. Conclusion: Our study suggests that high use of loss-based selection and high use of compensation strategies in older employees is positively related with OCB as perceived by their colleagues. However, high use of compensation strategies in younger employees is perceived negatively related with OCB. Our findings contribute to a better understanding of the age-differentiated interpersonal effects of successful aging strategies in terms of SOC in organizations. PMID:29085315

  7. An event-related brain potential study of visual selective attention to conjunctions of color and shape.

    PubMed

    Smid, H G; Jakob, A; Heinze, H J

    1999-03-01

    What cognitive processes underlie event-related brain potential (ERP) effects related to visual multidimensional selective attention and how are these processes organized? We recorded ERPs when participants attended to one conjunction of color, global shape and local shape and ignored other conjunctions of these attributes in three discriminability conditions. Attending to color and shape produced three ERP effects: frontal selection positivity (FSP), central negativity (N2b), and posterior selection negativity (SN). The results suggested that the processes underlying SN and N2b perform independent within-dimension selections, whereas the process underlying the FSP performs hierarchical between-dimension selections. At posterior electrodes, manipulation of discriminability changed the ERPs to the relevant but not to the irrelevant stimuli, suggesting that the SN does not concern the selection process itself but rather a cognitive process initiated after selection is finished. Other findings suggested that selection of multiple visual attributes occurs in parallel.

  8. Detection of Fundus Lesions Using Classifier Selection

    NASA Astrophysics Data System (ADS)

    Nagayoshi, Hiroto; Hiramatsu, Yoshitaka; Sako, Hiroshi; Himaga, Mitsutoshi; Kato, Satoshi

    A system for detecting fundus lesions caused by diabetic retinopathy from fundus images is being developed. The system can screen the images in advance in order to reduce the inspection workload on doctors. One of the difficulties that must be addressed in completing this system is how to remove false positives (which tend to arise near blood vessels) without decreasing the detection rate of lesions in other areas. To overcome this difficulty, we developed classifier selection according to the position of a candidate lesion, and we introduced new features that can distinguish true lesions from false positives. A system incorporating classifier selection and these new features was tested in experiments using 55 fundus images with some lesions and 223 images without lesions. The results of the experiments confirm the effectiveness of the proposed system, namely, degrees of sensitivity and specificity of 98% and 81%, respectively.

  9. The mere exposure effect is modulated by selective attention but not visual awareness.

    PubMed

    Huang, Yu-Feng; Hsieh, Po-Jang

    2013-10-18

    Repeated exposures to an object will lead to an enhancement of evaluation toward that object. Although this mere exposure effect may occur when the objects are presented subliminally, the role of conscious perception per se on evaluation has never been examined. Here we use a binocular rivalry paradigm to investigate whether a variance in conscious perceptual duration of faces has an effect on their subsequent evaluation, and how selective attention and memory interact with this effect. Our results show that face evaluation is positively biased by selective attention but not affected by visual awareness. Furthermore, this effect is not due to participants recalling which face had been attended to. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Research on detecting spot selection and signal pretreatment of four-quadrant detector

    NASA Astrophysics Data System (ADS)

    Liu, Wenli; Han, Shaokun

    2018-01-01

    The four-quadrant detector is a photoelectric position sensor based on the photovoltaic effect. It is widely used in many fields such as target azimuth measurement, end-guided weapon and so on. The selection of the spot and the calculation of the center position are one of the main factors that affect the accuracy of the position measurement of the fourquadrant detector. In order to improve the positioning accuracy of the four-quadrant detector, the method of determining the best spot size is obtained from the theoretical research. The output signal of the four-quadrant detector is a weak narrow pulse signal, which needs to be magnified and widened at high magnitudes. The signal preprocessing method is simulated and experimentally studied. Detecting the spot and the signal processing is realized by the four-quadrant detector, which is important for the use of quadrant detectors for high-precision position measurements.

  11. GABAB Receptor Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

    PubMed Central

    Lhuillier, Loic; Mombereau, Cedric; Cryan, John F.; Kaupmann, Klemens

    2006-01-01

    Exposure to cocaine induces selective behavioral and molecular adaptations. In rodents, acute cocaine induces increased locomotor activity whereas prolonged drug exposure results in behavioral locomotor sensitization, which is thought to be a consequence of drug–induced neuroadaptive changes. Recent attention has been given to compounds activating GABAB receptors as potential anti-addictive therapies. In particular the principle of allosteric positive GABAB receptor modulators is very promising in this respect, as positive modulators lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. Here we investigated the effects of systemic application of the GABAB receptor positive modulator GS39783 in animals treated with acute and chronic cocaine administration. Both GS39783 and baclofen dose-dependently attenuated acute cocaine-induced hyperlocomotion. Furthermore, both compounds also efficiently blocked cocaine-induced Fos induction in the striatal complex. In chronic studies GS39783 induced a modest attenuation of cocaine-induced locomotor sensitization. Chronic cocaine induces the accumulation of the transcription factor ΔFosB and up regulates cAMP-response-element-binding-protein (CREB) and dopamine-and-cAMP-regulated-phosphoprotein of 32 kd (DARPP-32). GS39783 blocked the induction/activation of DARPP-32 and CREB in the nucleus accumbens and dorsal striatum and partially inhibited ΔFosB accumulation in the dorsal striatum. In summary our data provide evidence that GS39783 attenuates the acute behavioral effects of cocaine exposure in rodents and in addition prevents the induction of selective long-term adaptive changes in dopaminergic signaling pathways. Further investigation of GABAB receptor positive modulation as a novel therapeutic strategy for the treatment of cocaine dependence and possibly other drugs of abuse is therefore warranted. PMID:16710312

  12. Situation Selection and Modification for Emotion Regulation in Younger and Older Adults

    PubMed Central

    Livingstone, Kimberly M.; Isaacowitz, Derek M.

    2016-01-01

    This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or “just view” condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation. PMID:26998196

  13. Signatures of positive selection in the cis-regulatory sequences of the human oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes.

    PubMed

    Schaschl, Helmut; Huber, Susanne; Schaefer, Katrin; Windhager, Sonja; Wallner, Bernard; Fieder, Martin

    2015-05-13

    The evolutionary highly conserved neurohypophyseal hormones oxytocin and arginine vasopressin play key roles in regulating social cognition and behaviours. The effects of these two peptides are meditated by their specific receptors, which are encoded by the oxytocin receptor (OXTR) and arginine vasopressin receptor 1a genes (AVPR1A), respectively. In several species, polymorphisms in these genes have been linked to various behavioural traits. Little, however, is known about whether positive selection acts on sequence variants in genes influencing variation in human behaviours. We identified, in both neuroreceptor genes, signatures of balancing selection in the cis-regulative acting sequences such as transcription factor binding and enhancer sequences, as well as in a transcriptional repressor sequence motif. Additionally, in the intron 3 of the OXTR gene, the SNP rs59190448 appears to be under positive directional selection. For rs59190448, only one phenotypical association is known so far, but it is in high LD' (>0.8) with loci of known association; i.e., variants associated with key pro-social behaviours and mental disorders in humans. Only for one SNP on the OXTR gene (rs59190448) was a sign of positive directional selection detected with all three methods of selection detection. For rs59190448, however, only one phenotypical association is known, but rs59190448 is in high LD' (>0.8), with variants associated with important pro-social behaviours and mental disorders in humans. We also detected various signatures of balancing selection on both neuroreceptor genes.

  14. 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

  15. 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.

  16. Higher Education: Reputation Effects, Signal Distortions, and Propitious Selection

    ERIC Educational Resources Information Center

    Savitskaya, E. V.; Altunina, N. S.

    2017-01-01

    We attempt to prove the hypothesis that, under certain conditions, a phenomenon of propitious selection may arise on the higher education market: When talented university entrants favor applying to branded universities, the latter are able to automatically build up a positive reputation without having to actually improve the quality of their…

  17. Isolation Effect in Immediate and Delayed Recall

    ERIC Educational Resources Information Center

    Bellezza, Francis S.; Cheney, Terry L.

    1973-01-01

    If the hypothesis of selective rehearsal is used to account for the isolation effect, then the recall of isolated items will depend both on the serial position of the isolated item and on whether recall is immediate or delayed. (Author)

  18. Attentional control mediates the effect of social anxiety on positive affect☆

    PubMed Central

    Morrison, Amanda S.; Heimberg, Richard G.

    2015-01-01

    The goal of the present studies was to examine whether attentional control, a self-regulatory attentional mechanism, mediates the effect of social anxiety on positive affect. We tested this mediation in two studies using undergraduate students selected to represent a broad range of severity of social anxiety. Self-report assessments of social anxiety, attentional control, and positive affect were collected in a cross-sectional design (Study 1) and in a longitudinal design with three assessment points (Study 2). Results of both studies supported the hypothesized mediational model. Specifically, social anxiety was inversely related to attentional control, which itself positively predicted positive affect. This mediation remained significant even when statistically controlling for the effects of depression. Additionally, the hypothesized model provided superior model fit to theoretically-grounded equivalent models in both studies. Implications of these findings for understanding diminished positive affect in social anxiety are discussed. PMID:23254261

  19. Mediators of Effects of a Selective Family-Focused Violence Prevention Approach for Middle School Students

    PubMed Central

    2013-01-01

    This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N=1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student’s valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth. PMID:21932067

  20. Light climate and dissolved organic carbon concentration influence species-specific changes in fish zooplanktivory

    USGS Publications Warehouse

    Weidel, Brian C.; Baglini, Katherine; Jones, Stuart E.; Kelly, Patrick T.; Solomon, Christopher T.; Zwart, Jacob A.

    2017-01-01

    Dissolved organic carbon (DOC) in lakes reduces light penetration and limits fish production in low nutrient lakes, reportedly via reduced primary and secondary production. Alternatively, DOC and light reductions could influence fish by altering their visual feeding. Previous studies report mixed effects of DOC on feeding rates of zooplanktivorous fish, but most investigators tested effects of a single concentration of DOC against clear-water, turbid, or algal treatments. We used a controlled laboratory study to quantify the effects of a DOC gradient (3–19 mg L−1) on average light climate and the zooplankton feeding rate of 3 common, north temperate fishes. Light availability, which was inversely related to DOC concentration, had a positive and linear effect on zooplankton consumption by juvenile largemouth bass (Micropterus salmoides) and bluegill (Lepomis macrochirus), explaining 22% and 28% of the variation in consumption, respectively. By contrast, zooplankton feeding rates by fathead minnow (Pimephales promelas) were best predicted by a nonlinear, negative influence of light (R2 = 0.13). In bluegill feeding trials we found a general trend for positive selection of larger zooplankton (Cladocera and Chaoboridae); however, the light climate did not influence the selection of prey type. Largemouth bass selected for larger-bodied zooplankton, with weak evidence that selectivity for large Cladocera changed from negative to neutral selection based on electivity values across the light gradient. Our results suggest that the effect of DOC on the light climate of lakes may directly influence fish zooplanktivory and that this influence may vary among fish species.

  1. 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.

  2. Aromatic Substitution Reactions: When You've Said Ortho, Meta, and Para, You Haven't Said It All.

    ERIC Educational Resources Information Center

    Traynham, James G.

    1983-01-01

    Recent investigations show that the ipso position competes effectively with unsubstituted positions in many aromatic substitution reactions, regardless of charge type of reaction. Selected examples available for nucleophilic, electrophilic, and free radical reactions are reviewed to suggest the range of ipso reactions. (JN)

  3. Behavior of the maximum likelihood in quantum state tomography

    NASA Astrophysics Data System (ADS)

    Scholten, Travis L.; Blume-Kohout, Robin

    2018-02-01

    Quantum state tomography on a d-dimensional system demands resources that grow rapidly with d. They may be reduced by using model selection to tailor the number of parameters in the model (i.e., the size of the density matrix). Most model selection methods typically rely on a test statistic and a null theory that describes its behavior when two models are equally good. Here, we consider the loglikelihood ratio. Because of the positivity constraint ρ ≥ 0, quantum state space does not generally satisfy local asymptotic normality (LAN), meaning the classical null theory for the loglikelihood ratio (the Wilks theorem) should not be used. Thus, understanding and quantifying how positivity affects the null behavior of this test statistic is necessary for its use in model selection for state tomography. We define a new generalization of LAN, metric-projected LAN, show that quantum state space satisfies it, and derive a replacement for the Wilks theorem. In addition to enabling reliable model selection, our results shed more light on the qualitative effects of the positivity constraint on state tomography.

  4. Behavior of the maximum likelihood in quantum state tomography

    DOE PAGES

    Blume-Kohout, Robin J; Scholten, Travis L.

    2018-02-22

    Quantum state tomography on a d-dimensional system demands resources that grow rapidly with d. They may be reduced by using model selection to tailor the number of parameters in the model (i.e., the size of the density matrix). Most model selection methods typically rely on a test statistic and a null theory that describes its behavior when two models are equally good. Here, we consider the loglikelihood ratio. Because of the positivity constraint ρ ≥ 0, quantum state space does not generally satisfy local asymptotic normality (LAN), meaning the classical null theory for the loglikelihood ratio (the Wilks theorem) shouldmore » not be used. Thus, understanding and quantifying how positivity affects the null behavior of this test statistic is necessary for its use in model selection for state tomography. We define a new generalization of LAN, metric-projected LAN, show that quantum state space satisfies it, and derive a replacement for the Wilks theorem. In addition to enabling reliable model selection, our results shed more light on the qualitative effects of the positivity constraint on state tomography.« less

  5. Behavior of the maximum likelihood in quantum state tomography

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

    Blume-Kohout, Robin J; Scholten, Travis L.

    Quantum state tomography on a d-dimensional system demands resources that grow rapidly with d. They may be reduced by using model selection to tailor the number of parameters in the model (i.e., the size of the density matrix). Most model selection methods typically rely on a test statistic and a null theory that describes its behavior when two models are equally good. Here, we consider the loglikelihood ratio. Because of the positivity constraint ρ ≥ 0, quantum state space does not generally satisfy local asymptotic normality (LAN), meaning the classical null theory for the loglikelihood ratio (the Wilks theorem) shouldmore » not be used. Thus, understanding and quantifying how positivity affects the null behavior of this test statistic is necessary for its use in model selection for state tomography. We define a new generalization of LAN, metric-projected LAN, show that quantum state space satisfies it, and derive a replacement for the Wilks theorem. In addition to enabling reliable model selection, our results shed more light on the qualitative effects of the positivity constraint on state tomography.« less

  6. 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.

  7. Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

    PubMed

    Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

    2012-01-01

    The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

  8. Visual working memory modulates low-level saccade target selection: Evidence from rapidly generated saccades in the global effect paradigm

    PubMed Central

    Hollingworth, Andrew; Matsukura, Michi; Luck, Steven J.

    2013-01-01

    In three experiments, we examined the influence of visual working memory (VWM) on the metrics of saccade landing position in a global effect paradigm. Participants executed a saccade to the more eccentric object in an object pair appearing on the horizontal midline, to the left or right of central fixation. While completing the saccade task, participants maintained a color in VWM for an unrelated memory task. Either the color of the saccade target matched the memory color (target match), the color of the distractor matched the memory color (distractor match), or the colors of neither object matched the memory color (no match). In the no-match condition, saccades tended to land at the midpoint between the two objects: the global, or averaging, effect. However, when one of the two objects matched VWM, the distribution of landing position shifted toward the matching object, both for target match and for distractor match. VWM modulation of landing position was observed even for the fastest quartile of saccades, with a mean latency as low as 112 ms. Effects of VWM on such rapidly generated saccades, with latencies in the express-saccade range, indicate that VWM interacts with the initial sweep of visual sensory processing, modulating perceptual input to oculomotor systems and thereby biasing oculomotor selection. As a result, differences in memory match produce effects on landing position similar to the effects generated by differences in physical salience. PMID:24190909

  9. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

    PubMed Central

    Byars, Sean G.; Gray, Lesley-Ann; Ripatti, Samuli; Stearns, Stephen C.; Inouye, Michael

    2017-01-01

    Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD. PMID:28640878

  10. Effect of framing on adolescents' decision making.

    PubMed

    Chien, Y C; Lin, C; Worthley, J

    1996-12-01

    92 young adolescents were tested using Tversky and Kahneman's (1981) decision problems for framing effects. A notable number of young adolescents tested were not influenced by the context of the decision problems, thus they selected the same response option for positively and negatively framed problems. Parallel information was not available in Tversky and Kahneman's study for adults because they used a between-subjects design. However, for present adolescents who selected different response options for different framing problems, the response pattern exhibited by them resembled the general pattern exhibited by the adults tested in Tversky and Kahneman's study-negative frames led them to accept risk to avoid certain loss; positive frames prevented them from risking what they were certain to gain. Boys and girls were similar in their susceptibility to framing effects as were honors students in mathematics as compared to nonhonors students. Although the positive vs negative framing only influenced some of the young adolescents tested in this study, because the influence was consistent, researchers and educators interested in adolescents' decisions involving risky choices might use framing principles to design and assess cognitive interventions for high-risk behaviors among young adolescents.

  11. Determining the Effect of Natural Selection on Linked Neutral Divergence across Species

    PubMed Central

    Phung, Tanya N.; Lohmueller, Kirk E.

    2016-01-01

    A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation. PMID:27508305

  12. Determining the Effect of Natural Selection on Linked Neutral Divergence across Species.

    PubMed

    Phung, Tanya N; Huber, Christian D; Lohmueller, Kirk E

    2016-08-01

    A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation.

  13. 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

  14. Designing Superoxide-Generating Quantum Dots for Selective Light-Activated Nanotherapy.

    PubMed

    Goodman, Samuel M; Levy, Max; Li, Fei-Fei; Ding, Yuchen; Courtney, Colleen M; Chowdhury, Partha P; Erbse, Annette; Chatterjee, Anushree; Nagpal, Prashant

    2018-01-01

    The rapid emergence of superbugs, or multi-drug resistant (MDR) organisms, has prompted a search for novel antibiotics, beyond traditional small-molecule therapies. Nanotherapeutics are being investigated as alternatives, and recently superoxide-generating quantum dots (QDs) have been shown as important candidates for selective light-activated therapy, while also potentiating existing antibiotics against MDR superbugs. Their therapeutic action is selective, can be tailored by simply changing their quantum-confined conduction-valence band (CB-VB) positions and alignment with different redox half-reactions-and hence their ability to generate specific radical species in biological media. Here, we show the design of superoxide-generating QDs using optimal QD material and size well-matched to superoxide redox potential, charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs with conduction band (CB) position at -0.5 V with respect to Normal Hydrogen Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective superoxide radicals, thereby demonstrating the effective light-activated therapy. Although the positively charged QDs demonstrate large cellular uptake, they bind indiscriminately to cell surfaces and cause non-selective cell death, while negatively charged and zwitterionic QD ligands reduce the uptake and allow selective therapeutic action via interaction with redox species. The stability of designed QDs in biologically-relevant media increases with the formation of core-shell QD structures, but an appropriate design of core-shell structures is needed to minimize any reduction in charge injection efficiency to adsorbed oxygen molecules (to form superoxide) and maintain similar quantitative generation of tailored redox species, as measured using electron paramagnetic resonance (EPR) spectroscopy and electrochemical impedance spectroscopy (EIS). Using these findings, we demonstrate the rational design of QDs as selective therapeutic to kill more than 99% of a priority class I pathogen, thus providing an effective therapy against MDR superbugs.

  15. The effects of memory load and stimulus relevance on the EEG during a visual selective memory search task: an ERP and ERD/ERS study.

    PubMed

    Gomarus, H Karin; Althaus, Monika; Wijers, Albertus A; Minderaa, Ruud B

    2006-04-01

    Psychophysiological correlates of selective attention and working memory were investigated in a group of 18 healthy children using a visually presented selective memory search task. Subjects had to memorize one (load1) or 3 (load3) letters (memory set) and search for these among a recognition set consisting of 4 letters only if the letters appeared in the correct (relevant) color. Event-related potentials (ERPs) as well as alpha and theta event-related synchronization and desynchronization (ERD/ERS) were derived from the EEG that was recorded during the task. In the ERP to the memory set, a prolonged load-related positivity was found. In response to the recognition set, effects of relevance were manifested in an early frontal positivity and a later frontal negativity. Effects of load were found in a search-related negativity within the attended category and a suppression of the P3-amplitude. Theta ERS was most pronounced for the most difficult task condition during the recognition set, whereas alpha ERD showed a load-effect only during memorization. The manipulation of stimulus relevance and memory load affected both ERP components and ERD/ERS. The present paradigm may supply a useful method for studying processes of selective attention and working memory and can be used to examine group differences between healthy controls and children showing psychopathology.

  16. 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

  17. Disentangling the Effect of Valence and Arousal on Judgments Concerning Moral Transgressions.

    PubMed

    de la Viña, Luis; Garcia-Burgos, David; Okan, Yasmina; Cándido, Antonio; González, Felisa

    2015-08-10

    An increasing body of research has investigated the effect of emotions on judgments concerning moral transgressions. Yet, few studies have controlled for arousal levels associated with the emotions. High arousal may affect moral processing by triggering attention to salient features of transgressions, independently of valence. Therefore previously documented differences in effects of negative and positive emotions may have been confounded by differences in arousal. We conducted two studies to shed light on this issue. In Study 1 we developed a questionnaire including vignettes selected on the basis of psychometrical properties (i.e., mean ratings of the actions and variability). This questionnaire was administered to participants in Study 2, after presenting them with selected pictures inducing different valence but equivalent levels of arousal. Negative pictures led to more severe moral judgments than neutral (p = .054, d = 0.60) and positive pictures (p = .002, d = 1.02), for vignettes that were not associated with extreme judgments. In contrast, positive pictures did not reliably affect judgments concerning such vignettes. These findings suggest that the observed effects of emotions cannot be accounted for by an increase in attention linked to the arousal which accompanies these emotions.

  18. Nonmathematical models for evolution of altruism, and for group selection (peck order-territoriality-ant colony-dual-determinant model-tri-determinant model).

    PubMed

    Darlington, P J

    1972-02-01

    Mathematical biologists have failed to produce a satisfactory general model for evolution of altruism, i.e., of behaviors by which "altruists" benefit other individuals but not themselves; kin selection does not seem to be a sufficient explanation of nonreciprocal altruism. Nonmathematical (but mathematically acceptable) models are now proposed for evolution of negative altruism in dual-determinant and of positive altruism in tri-determinant systems. Peck orders, territorial systems, and an ant society are analyzed as examples. In all models, evolution is primarily by individual selection, probably supplemented by group selection. Group selection is differential extinction of populations. It can act only on populations preformed by selection at the individual level, but can either cancel individual selective trends (effecting evolutionary homeostasis) or supplement them; its supplementary effect is probably increasingly important in the evolution of increasingly organized populations.

  19. Magnetic Resonance Imaging Assessment of Intra-Articular Structures in the Canine Stifle Joint after Implantation of a Titanium Tibial Plateau Levelling Osteotomy Plate.

    PubMed

    Feichtenschlager, Christian; Gerwing, Martin; Failing, Klaus; Peppler, Christine; Kása, Andreas; Kramer, Martin; von Pückler, Kerstin H

    2018-06-02

     To determine the effectiveness of magnetic resonance imaging (MRI) in the evaluation of anatomical stifle structures with respect to implant positioning after tibial plateau levelling osteotomy (TPLO) using a titanium plate.  Selected sagittal and dorsal sequences of pre- and postoperative MRI (1.0 T scanner) of 13 paired ( n  = 26) sound cadaveric stifle joints were evaluated. The effect of susceptibility artifact on adjacent anatomical stifle structures was graded from 0 to 5. The impact of implant positioning regarding assessment score was calculated using Spearman's rank correlation coefficient.  Sagittal turbo spin echo (TSE)-acquired images enabled interpretation of most soft tissue, osseous and cartilage structures without detrimental effect of susceptibility artifact distortions. In T2-weighted TSE images, the cranial cruciate ligament and caudal horn of the medial meniscus could be evaluated, independent of implant position, without any susceptibility artifact in all specimens. T2-weighted fast field echo, water selective, balanced fast field echo and short tau inversion recovery were most markedly affected by susceptibility artifact.  In selected TSE sequences, MRI allows evaluation of critical intra-articular structures after titanium TPLO plate implantation. Further investigations with confirmed stifle pathologies in dogs are required, to evaluate the accuracy of MRI after TPLO in clinical cases in this context. Schattauer GmbH Stuttgart.

  20. Selection of Drought Tolerant Maize Hybrids Using Path Coefficient Analysis and Selection Index.

    PubMed

    Dao, Abdalla; Sanou, Jacob; V S Traore, Edgar; Gracen, Vernon; Danquah, Eric Y

    2017-01-01

    In drought-prone environments, direct selection for yield is not adequate because of the variable environment and genotype x environment interaction. Therefore, the use of secondary traits in addition to yield has been suggested. The relative usefulness of secondary traits as indirect selection criteria for maize grain yield is determined by the magnitudes of their genetic variance, heritability and genetic correlation with the grain yield. Forty eight testcross hybrids derived from lines with different genetic background and geographical origins plus 7 checks were evaluated in both well-watered and water-stressed conditions over two years for grain yield and secondary traits to determine the most appropriate secondary traits and select drought tolerant hybrids. Study found that broad-sense heritability of grain yield and Ear Per Plant (EPP) increased under drought stress. Ear aspect (EASP) and ear height (EHT) had larger correlation coefficients and direct effect on grain yield but in opposite direction, negative and positive respectively. Traits like, EPP, Tassel Size (TS) and Plant Recovery (PR) contributed to increase yield via EASP by a large negative indirect effect. Under drought stress, EHT had positive and high direct effect and negative indirect effect via plant height on grain yield indicating that the ratio between ear and plant heights (R-EPH) was associated to grain yield. Path coefficient analysis showed that traits EPP, TS, PR, EASP, R-EPH were important secondary traits in the present experiment. These traits were used in a selection index to classify hybrids according to their performance under drought. The selection procedure included also a Relative Decrease in Yield (RDY) index. Some secondary traits reported as significant selection criteria for selection under drought stress were not finally established in the present study. This is because the relationship between grain and secondary traits can be affected by various factors including germplasm, environment and applied statistical analysis. Therefore, different traits and selection procedure should be applied in the selection process of drought tolerant genotypes for diverse genetic materials and growing conditions.

  1. Cone of Darkness: Finding Blank-sky Positions for Multi-object Wide-field Observations

    NASA Astrophysics Data System (ADS)

    Lorente, N. P. F.

    2014-05-01

    We present the Cone of Darkness, an application to automatically configure blank-sky positions for a series of stacked, wide-field observations, such as those carried out by the SAMI instrument on the Anglo-Australian Telescope (AAT). The Sydney-AAO Multi-object Integral field spectrograph (SAMI) uses a plug-plate to mount its 13×61 core imaging fibre bundles (hexabundles) in the optical plane at the telescope's prime focus. To make the most efficient use of each plug-plate, several observing fields are typically stacked to produce a single plate. When choosing blank-sky positions for the observations it is most effective to select these such that one set of 26 holes gives valid sky positions for all fields on the plate. However, when carried out manually this selection process is tedious and includes a significant risk of error. The Cone of Darkness software aims to provide uniform blank-sky position coverage over the field of observation, within the limits set by the distribution of target positions and the chosen input catalogs. This will then facilitate the production of the best representative median sky spectrum for use in sky subtraction. The application, written in C++, is configurable, making it usable for a range of instruments. Given the plate characteristics and the positions of target holes, the software segments the unallocated space on the plate and determines the position which best fits the uniform distribution requirement. This position is checked, for each field, against the selected catalog using a TAP ADQL search. The process is then repeated until the desired number of sky positions is attained.

  2. Selection for intramuscular fat and lean meat yield will improve the bloomed colour of Australian lamb loin meat.

    PubMed

    Calnan, H B; Jacob, R H; Pethick, D W; Gardner, G E

    2017-09-01

    The colour of bloomed m. longissimus was measured 24h post slaughter for 8165 lamb carcasses produced over 5years across 8 sites in Australia. Intramuscular fat across a 2 to 8% range and shortloin fat weight were positively associated with meat lightness (L*), redness (a*), yellowness (b*), hue and chroma (P<0.01). Shortloin muscle weight was negatively associated with these meat colour parameters (P<0.01), although this was largely accounted for by correlated changes in intramuscular fat (P<0.01). The effect of sire breeding values for lamb weight, shortloin muscle depth and fat depth on loin L*, a*, b*, hue and chroma were small and varied between lambs of different sire type, dam breed and sex. Thus selection for lean meat yield will have neutral or positive effects on meat colour, while selection for increased intramuscular fat will make the bloomed colour of lamb meat lighter and redder. Copyright © 2017. Published by Elsevier Ltd.

  3. Forest fragmentation and selective logging have inconsistent effects on multiple animal-mediated ecosystem processes in a tropical forest.

    PubMed

    Schleuning, Matthias; Farwig, Nina; Peters, Marcell K; Bergsdorf, Thomas; Bleher, Bärbel; Brandl, Roland; Dalitz, Helmut; Fischer, Georg; Freund, Wolfram; Gikungu, Mary W; Hagen, Melanie; Garcia, Francisco Hita; Kagezi, Godfrey H; Kaib, Manfred; Kraemer, Manfred; Lung, Tobias; Naumann, Clas M; Schaab, Gertrud; Templin, Mathias; Uster, Dana; Wägele, J Wolfgang; Böhning-Gaese, Katrin

    2011-01-01

    Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the functionality of tropical forests can be maintained in moderately disturbed forest fragments. Conservation concepts for tropical forests should thus include not only remaining pristine forests but also functionally viable forest remnants.

  4. Forest Fragmentation and Selective Logging Have Inconsistent Effects on Multiple Animal-Mediated Ecosystem Processes in a Tropical Forest

    PubMed Central

    Schleuning, Matthias; Farwig, Nina; Peters, Marcell K.; Bergsdorf, Thomas; Bleher, Bärbel; Brandl, Roland; Dalitz, Helmut; Fischer, Georg; Freund, Wolfram; Gikungu, Mary W.; Hagen, Melanie; Garcia, Francisco Hita; Kagezi, Godfrey H.; Kaib, Manfred; Kraemer, Manfred; Lung, Tobias; Schaab, Gertrud; Templin, Mathias; Uster, Dana; Wägele, J. Wolfgang; Böhning-Gaese, Katrin

    2011-01-01

    Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the functionality of tropical forests can be maintained in moderately disturbed forest fragments. Conservation concepts for tropical forests should thus include not only remaining pristine forests but also functionally viable forest remnants. PMID:22114695

  5. Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression

    PubMed Central

    Wells, Tony T.; Clerkin, Elise M.; Ellis, Alissa J.; Beevers, Christopher G.

    2013-01-01

    Objective Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy participants. This effect is likely relevant to the therapeutic actions of these medications, but has not been studied in patients with Major Depressive Disorder (MDD) taking antidepressants as typically prescribed in the community. Method The authors examined the effects of antidepressant medication on selective attention for emotional stimuli using eye tracking in a sample of 47 participants (21 medicated; 26 non-medicated) with MDD and 47 matched, non-depressed controls. Participants completed a passive viewing eye tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Results: Depressed participants currently taking antidepressant medication and non-depressed healthy control participants demonstrated greater total gaze duration and more fixations for positive stimuli, compared to non-medicated depressed participants. Depressed participants on medication (vs. depressed participants not on medication) also had fewer fixations for dysphoric stimuli. Conclusions Antidepressants, as prescribed in the community to depressed patients, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with prior work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication. PMID:24030200

  6. Effect of antidepressant medication use on emotional information processing in major depression.

    PubMed

    Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J; Beevers, Christopher G

    2014-02-01

    Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

  7. Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

    PubMed Central

    Liu, J; Turnbough, C L

    1994-01-01

    In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

  8. Education and the Transition to Fatherhood: The Role of Selection Into Union.

    PubMed

    Trimarchi, Alessandra; Van Bavel, Jan

    2017-02-01

    Although advanced education has been found to be consistently associated with a later transition to parenthood for women, findings about education and the transition to parenthood have been much less consistent for men, and no stylized fact has emerged from the literature. We argue that the inconsistency of findings for men is due to the fact that the selection process involved in union formation has been disregarded in earlier studies. We hypothesize that men's educational attainment consistently and positively affects the transition to fatherhood via higher rates of union formation. We apply multiprocess event-history analysis to data from the Generations and Gender Surveys for 10 European countries. Our results show indeed a consistent positive effect of education on the transition to fatherhood, but it operates chiefly through selection into union. Failing to account for this selection process leads to a major underestimation of the salience of education for the transition to fatherhood.

  9. 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.

  10. How voluntary prenatal diagnosis and selective abortion increase the abnormal human gene pool.

    PubMed

    Boss, J A

    1990-06-01

    It is often assumed that prenatal diagnosis followed by the selective abortion of "defective" fetuses has a positive eugenic effect. Although mandatory selective abortion of "defective" fetuses and, more important, carriers would tend to reduce the number of deleterious genes in the gene pool, the present program of voluntary prenatal diagnosis and selective abortion actually increases the number of deleterious genes. This raises the issue of freedom of choice regarding selective abortion and societal pressure on parents to undergo prenatal testing and to abort their fetus should it have a genetic disorder or be a carrier of one.

  11. 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.

  12. Seeing the world through rose-colored glasses: People who are happy and satisfied with life preferentially attend to positive stimuli.

    PubMed

    Raila, Hannah; Scholl, Brian J; Gruber, June

    2015-08-01

    Given the many benefits conferred by trait happiness and life satisfaction, a primary goal is to determine how these traits relate to underlying cognitive processes. For example, visual attention acts as a gateway to awareness, raising the question of whether happy and satisfied people attend to (and therefore see) the world differently. Previous work suggests that biases in selective attention are associated with both trait negativity and with positive affect states, but to our knowledge, no previous work has explored whether trait-happy individuals attend to the world differently. Here, we employed eye tracking as a continuous measure of sustained overt attention during passive viewing of displays containing positive and neutral photographs to determine whether selective attention to positive scenes is associated with measures of trait happiness and life satisfaction. Both trait measures were significantly correlated with selective attention for positive (vs. neutral) scenes, and this general pattern was robust across several types of positive stimuli (achievement, social, and primary reward), and not because of positive or negative state affect. Such effects were especially prominent during the later phases of sustained viewing. This suggests that people who are happy and satisfied with life may literally see the world in a more positive light, as if through rose-colored glasses. Future work should investigate the causal relationship between such attention biases and one's happiness and life satisfaction. (c) 2015 APA, all rights reserved).

  13. Validation of candidate gene markers for marker-assisted selection of potato cultivars with improved tuber quality.

    PubMed

    Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane

    2013-04-01

    Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were identified that significantly improved average chip quality after cold storage and tuber starch content. In F1 progeny of a single-cross combination, MAS with six markers did not give the expected result. Reasons and implications for MAS in potato are discussed.

  14. Avian responses to selective logging shaped by species traits and logging practices

    PubMed Central

    Burivalova, Zuzana; Lee, Tien Ming; Giam, Xingli; Şekercioğlu, Çağan Hakkı; Wilcove, David S.; Koh, Lian Pin

    2015-01-01

    Selective logging is one of the most common forms of forest use in the tropics. Although the effects of selective logging on biodiversity have been widely studied, there is little agreement on the relationship between life-history traits and tolerance to logging. In this study, we assessed how species traits and logging practices combine to determine species responses to selective logging, based on over 4000 observations of the responses of nearly 1000 bird species to selective logging across the tropics. Our analysis shows that species traits, such as feeding group and body mass, and logging practices, such as time since logging and logging intensity, interact to influence a species' response to logging. Frugivores and insectivores were most adversely affected by logging and declined further with increasing logging intensity. Nectarivores and granivores responded positively to selective logging for the first two decades, after which their abundances decrease below pre-logging levels. Larger species of omnivores and granivores responded more positively to selective logging than smaller species from either feeding group, whereas this effect of body size was reversed for carnivores, herbivores, frugivores and insectivores. Most importantly, species most negatively impacted by selective logging had not recovered approximately 40 years after logging cessation. We conclude that selective timber harvest has the potential to cause large and long-lasting changes in avian biodiversity. However, our results suggest that the impacts can be mitigated to a certain extent through specific forest management strategies such as lengthening the rotation cycle and implementing reduced impact logging. PMID:25994673

  15. Crystal-Site-Selective Spectrum of Fe3BO6 by Synchrotron Mössbauer Diffraction with Pure Nuclear Bragg Scattering

    NASA Astrophysics Data System (ADS)

    Nakamura, Shin; Mitsui, Takaya; Fujiwara, Kosuke; Ikeda, Naoshi; Kurokuzu, Masayuki; Shimomura, Susumu

    2017-08-01

    We have succeeded in obtaining the crystal-site-selective spectra of the collinear antiferromagnet Fe3BO6 using a synchrotron Mössbauer diffractometer with pure nuclear Bragg scattering at SPring-8 BL11XU. Well-resolved 300, 500, and 700 reflection spectra, having asymmetric line shapes owing to the higher-order interference effect between the nuclear energy levels, were quantitatively analyzed using a formula based on the dynamical theory of diffraction. Reasonable hyperfine parameters were obtained. The intensity ratio of Fe1 to Fe2 subspectra is in accordance with the nuclear structure factor. However, when the spectrum is measured at the peak position of the rocking curve (very near the Bragg position), the value of the center shift deviates from its intrinsic value. This is also due to the dynamical effect of γ-ray diffraction. To avoid this problem, it is necessary to use diffraction angles near the foot of the rocking curve, approximately 0.02° apart from the peak position.

  16. Amnesia, rehearsal, and temporal distinctiveness models of recall.

    PubMed

    Brown, Gordon D A; Della Sala, Sergio; Foster, Jonathan K; Vousden, Janet I

    2007-04-01

    Classical amnesia involves selective memory impairment for temporally distant items in free recall (impaired primacy) together with relative preservation of memory for recency items. This abnormal serial position curve is traditionally taken as evidence for a distinction between different memory processes, with amnesia being associated with selectively impaired long-term memory. However recent accounts of normal serial position curves have emphasized the importance of rehearsal processes in giving rise to primacy effects and have suggested that a single temporal distinctiveness mechanism can account for both primacy and recency effects when rehearsal is considered. Here we explore the pattern of strategic rehearsal in a patient with very severe amnesia. When the patient's rehearsal pattern is taken into account, a temporal distinctiveness model can account for the serial position curve in both amnesic and control free recall. The results are taken as consistent with temporal distinctiveness models of free recall, and they motivate an emphasis on rehearsal patterns in understanding amnesic deficits in free recall.

  17. Goal-Side Selection in Soccer Penalty Kicking When Viewing Natural Scenes

    PubMed Central

    Weigelt, Matthias; Memmert, Daniel

    2012-01-01

    The present study investigates the influence of goalkeeper displacement on goal-side selection in soccer penalty kicking. Facing a penalty situation, participants viewed photo-realistic images of a goalkeeper and a soccer goal. In the action selection task, they were asked to kick to the greater goal-side, and in the perception task, they indicated the position of the goalkeeper on the goal line. To this end, the goalkeeper was depicted in a regular goalkeeping posture, standing either in the exact middle of the goal or being displaced at different distances to the left or right of the goal’s center. Results showed that the goalkeeper’s position on the goal line systematically affected goal-side selection, even when participants were not aware of the displacement. These findings provide further support for the notion that the implicit processing of the stimulus layout in natural scenes can effect action selection in complex environments, such in soccer penalty shooting. PMID:22973246

  18. Serial Position Curves in Free Recall

    ERIC Educational Resources Information Center

    Laming, Donald

    2010-01-01

    The scenario for free recall set out in Laming (2009) is developed to provide models for the serial position curves from 5 selected sets of data, for final free recall, and for multitrial free recall. The 5 sets of data reflect the effects of rate of presentation, length of list, delay of recall, and suppression of rehearsal. Each model…

  19. The Efficacy of Positive Behavioural Support with the Most Challenging Behaviour: The Evidence and Its Implications

    ERIC Educational Resources Information Center

    LaVigna, Gary W.; Willis, Thomas J.

    2012-01-01

    Background: Positive behaviour support (PBS) is behaviour analysis applied in support of people with challenging behaviour. Questions have been raised as to PBS effectiveness, costs, and accessibility. Method: Outcome studies meeting specified criteria for PBS were selected for review. All told, 12 outcome studies encompassing 423 cases were…

  20. Default Bayes Factors for Model Selection in Regression

    ERIC Educational Resources Information Center

    Rouder, Jeffrey N.; Morey, Richard D.

    2012-01-01

    In this article, we present a Bayes factor solution for inference in multiple regression. Bayes factors are principled measures of the relative evidence from data for various models or positions, including models that embed null hypotheses. In this regard, they may be used to state positive evidence for a lack of an effect, which is not possible…

  1. Sexual Orientation and Spatial Position Effects on Selective Forms of Object Location Memory

    ERIC Educational Resources Information Center

    Rahman, Qazi; Newland, Cherie; Smyth, Beatrice Mary

    2011-01-01

    Prior research has demonstrated robust sex and sexual orientation-related differences in object location memory in humans. Here we show that this sexual variation may depend on the spatial position of target objects and the task-specific nature of the spatial array. We tested the recovery of object locations in three object arrays (object…

  2. Processing Distracting Non-face Emotional Images: No Evidence of an Age-Related Positivity Effect

    PubMed Central

    Madill, Mark; Murray, Janice E.

    2017-01-01

    Cognitive aging may be accompanied by increased prioritization of social and emotional goals that enhance positive experiences and emotional states. The socioemotional selectivity theory suggests this may be achieved by giving preference to positive information and avoiding or suppressing negative information. Although there is some evidence of a positivity bias in controlled attention tasks, it remains unclear whether a positivity bias extends to the processing of affective stimuli presented outside focused attention. In two experiments, we investigated age-related differences in the effects of to-be-ignored non-face affective images on target processing. In Experiment 1, 27 older (64–90 years) and 25 young adults (19–29 years) made speeded valence judgments about centrally presented positive or negative target images taken from the International Affective Picture System. To-be-ignored distractor images were presented above and below the target image and were either positive, negative, or neutral in valence. The distractors were considered task relevant because they shared emotional characteristics with the target stimuli. Both older and young adults responded slower to targets when distractor valence was incongruent with target valence relative to when distractors were neutral. Older adults responded faster to positive than to negative targets but did not show increased interference effects from positive distractors. In Experiment 2, affective distractors were task irrelevant as the target was a three-digit array and did not share emotional characteristics with the distractors. Twenty-six older (63–84 years) and 30 young adults (18–30 years) gave speeded responses on a digit disparity task while ignoring the affective distractors positioned in the periphery. Task performance in either age group was not influenced by the task-irrelevant affective images. In keeping with the socioemotional selectivity theory, these findings suggest that older adults preferentially process task-relevant positive non-face images but only when presented within the main focus of attention. PMID:28450848

  3. Processing Distracting Non-face Emotional Images: No Evidence of an Age-Related Positivity Effect.

    PubMed

    Madill, Mark; Murray, Janice E

    2017-01-01

    Cognitive aging may be accompanied by increased prioritization of social and emotional goals that enhance positive experiences and emotional states. The socioemotional selectivity theory suggests this may be achieved by giving preference to positive information and avoiding or suppressing negative information. Although there is some evidence of a positivity bias in controlled attention tasks, it remains unclear whether a positivity bias extends to the processing of affective stimuli presented outside focused attention. In two experiments, we investigated age-related differences in the effects of to-be-ignored non-face affective images on target processing. In Experiment 1, 27 older (64-90 years) and 25 young adults (19-29 years) made speeded valence judgments about centrally presented positive or negative target images taken from the International Affective Picture System. To-be-ignored distractor images were presented above and below the target image and were either positive, negative, or neutral in valence. The distractors were considered task relevant because they shared emotional characteristics with the target stimuli. Both older and young adults responded slower to targets when distractor valence was incongruent with target valence relative to when distractors were neutral. Older adults responded faster to positive than to negative targets but did not show increased interference effects from positive distractors. In Experiment 2, affective distractors were task irrelevant as the target was a three-digit array and did not share emotional characteristics with the distractors. Twenty-six older (63-84 years) and 30 young adults (18-30 years) gave speeded responses on a digit disparity task while ignoring the affective distractors positioned in the periphery. Task performance in either age group was not influenced by the task-irrelevant affective images. In keeping with the socioemotional selectivity theory, these findings suggest that older adults preferentially process task-relevant positive non-face images but only when presented within the main focus of attention.

  4. Transcriptome sequencing of Eucalyptus camaldulensis seedlings subjected to water stress reveals functional single nucleotide polymorphisms and genes under selection

    PubMed Central

    2012-01-01

    Background Water stress limits plant survival and production in many parts of the world. Identification of genes and alleles responding to water stress conditions is important in breeding plants better adapted to drought. Currently there are no studies examining the transcriptome wide gene and allelic expression patterns under water stress conditions. We used RNA sequencing (RNA-seq) to identify the candidate genes and alleles and to explore the evolutionary signatures of selection. Results We studied the effect of water stress on gene expression in Eucalyptus camaldulensis seedlings derived from three natural populations. We used reference-guided transcriptome mapping to study gene expression. Several genes showed differential expression between control and stress conditions. Gene ontology (GO) enrichment tests revealed up-regulation of 140 stress-related gene categories and down-regulation of 35 metabolic and cell wall organisation gene categories. More than 190,000 single nucleotide polymorphisms (SNPs) were detected and 2737 of these showed differential allelic expression. Allelic expression of 52% of these variants was correlated with differential gene expression. Signatures of selection patterns were studied by estimating the proportion of nonsynonymous to synonymous substitution rates (Ka/Ks). The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that most of the genes are under purifying selection. Among the positively selected genes (Ka/Ks > 1.5) apoptosis and cell death categories were enriched. Of the 287 positively selected genes, ninety genes showed differential expression and 27 SNPs from 17 positively selected genes showed differential allelic expression between treatments. Conclusions Correlation of allelic expression of several SNPs with total gene expression indicates that these variants may be the cis-acting variants or in linkage disequilibrium with such variants. Enrichment of apoptosis and cell death gene categories among the positively selected genes reveals the past selection pressures experienced by the populations used in this study. PMID:22853646

  5. Correlation, path analysis and heritability estimation for agronomic traits contribute to yield on soybean

    NASA Astrophysics Data System (ADS)

    Sulistyo, A.; Purwantoro; Sari, K. P.

    2018-01-01

    Selection is a routine activity in plant breeding programs that must be done by plant breeders in obtaining superior plant genotypes. The use of appropriate selection criteria will determine the effectiveness of selection activities. The purpose of this study was to analysis the inheritable agronomic traits that contribute to soybean yield. A total of 91 soybean lines were planted in Muneng Experimental Station, Probolinggo District, East Java Province, Indonesia in 2016. All soybean lines were arranged in randomized complete block design with two replicates. Correlation analysis, path analysis and heritability estimation were performed on days to flowering, days to maturing, plant height, number of branches, number of fertile nodes, number of filled pods, weight of 100 seeds, and yield to determine selection criteria on soybean breeding program. The results showed that the heritability value of almost all agronomic traits observed is high except for the number of fertile nodes with low heritability. The result of correlation analysis shows that days to flowering, plant height and number of fertile nodes have positive correlation with seed yield per plot (0.056, 0.444, and 0.100, respectively). In addition, path analysis showed that plant height and number of fertile nodes have highest positive direct effect on soybean yield. Based on this result, plant height can be selected as one of selection criteria in soybean breeding program to obtain high yielding soybean variety.

  6. A highly sensitive and selective fluorescent sensor for detection of sulfide anion based on the steric hindrance effect

    NASA Astrophysics Data System (ADS)

    Chen, Guanfan; Tang, Mengzhuo; Fu, Xiufang; Cheng, Fenmin; Zou, Xianghua; Wang, Jingpei; Zeng, Rongjin

    2018-01-01

    Sulfide anions are not only generated as a byproduct from industrial processes but also as a crucial kind of element in biological systems. Therefore, fluorescent probes for detecting sulfide anion with sensitive and selective characters are highly popular. In this study, we report a highly sensitive and selective fluorescent sensor M1 for detection of sulfide anion based on the steric hindrance effect, where the recognition unit, dinitrobenzenesulfonate ester group is linked to aromatic ortho-position in the porphyrin, and correspondingly the fluorescence of fluorescein is efficiently quenched. Compared with the sensors with recognition unit linked to the other aromatic positions, the fluorescent sensor M1 has a lower fluorescence background. Furthermore, the corresponding fluorescence responses (F/F0) of M1 for mercapto amino-acid GSH, Hcy and Cys, were all far lower than the relative fluorescence ratio F/F0 values for S2-. It means that M1 is sensitive and selective to detection of S2-, and has an anti-disturbance ability to the biologically-relevant thiols, GSH, Hcy and Cys, and has the prospect of application in the exact detection of sulfide anions in living organisms. This approach offers some useful insights for realizing sensitive and selective fluorescent turn-on sensing in the detection assays for other analytes.

  7. Intraspecific genetic diversity and composition modify species-level diversity-productivity relationships.

    PubMed

    Schöb, Christian; Kerle, Sarah; Karley, Alison J; Morcillo, Luna; Pakeman, Robin J; Newton, Adrian C; Brooker, Rob W

    2015-01-01

    Biodiversity regulates ecosystem functions such as productivity, and experimental studies of species mixtures have revealed selection and complementarity effects driving these responses. However, the impacts of intraspecific genotypic diversity in these studies are unknown, despite it forming a substantial part of the biodiversity. In a glasshouse experiment we constructed plant communities with different levels of barley (Hordeum vulgare) genotype and weed species diversity and assessed their relative biodiversity effects through additive partitioning into selection and complementarity effects. Barley genotype diversity had weak positive effects on aboveground biomass through complementarity effects, whereas weed species diversity increased biomass predominantly through selection effects. When combined, increasing genotype diversity of barley tended to dilute the selection effect of weeds. We interpret these different effects of barley genotype and weed species diversity as the consequence of small vs large trait variation associated with intraspecific barley diversity and interspecific weed diversity, respectively. The different effects of intra- vs interspecific diversity highlight the underestimated and overlooked role of genetic diversity for ecosystem functioning. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  8. Marker-Assisted Introgression in Backcross Breeding Programs

    PubMed Central

    Visscher, P. M.; Haley, C. S.; Thompson, R.

    1996-01-01

    The efficiency of marker-assisted introgression in backcross populations derived from inbred lines was investigated by simulation. Background genotypes were simulated assuming that a genetic model of many genes of small effects in coupling phase explains the observed breed difference and variance in backcross populations. Markers were efficient in introgression backcross programs for simultaneously introgressing an allele and selecting for the desired genomic background. Using a marker spacing of 10-20 cM gave an advantage of one to two backcross generations selection relative to random or phenotypic selection. When the position of the gene to be introgressed is uncertain, for example because its position was estimated from a trait gene mapping experiment, a chromosome segment should be introgressed that is likely to include the allele of interest. Even for relatively precisely mapped quantitative trait loci, flanking markers or marker haplotypes should cover ~10-20 cM around the estimated position of the gene, to ensure that the allele frequency does not decline in later backcross generations. PMID:8978075

  9. Weak lensing magnification in the Dark Energy Survey Science Verification data

    NASA Astrophysics Data System (ADS)

    Garcia-Fernandez, M.; Sanchez, E.; Sevilla-Noarbe, I.; Suchyta, E.; Huff, E. M.; Gaztanaga, E.; Aleksić, J.; Ponce, R.; Castander, F. J.; Hoyle, B.; Abbott, T. M. C.; Abdalla, F. B.; Allam, S.; Annis, J.; Benoit-Lévy, A.; Bernstein, G. M.; Bertin, E.; Brooks, D.; Buckley-Geer, E.; Burke, D. L.; Carnero Rosell, A.; Carrasco Kind, M.; Carretero, J.; Crocce, M.; Cunha, C. E.; D'Andrea, C. B.; da Costa, L. N.; DePoy, D. L.; Desai, S.; Diehl, H. T.; Eifler, T. F.; Evrard, A. E.; Fernandez, E.; Flaugher, B.; Fosalba, P.; Frieman, J.; García-Bellido, J.; Gerdes, D. W.; Giannantonio, T.; Gruen, D.; Gruendl, R. A.; Gschwend, J.; Gutierrez, G.; James, D. J.; Jarvis, M.; Kirk, D.; Krause, E.; Kuehn, K.; Kuropatkin, N.; Lahav, O.; Lima, M.; MacCrann, N.; Maia, M. A. G.; March, M.; Marshall, J. L.; Melchior, P.; Miquel, R.; Mohr, J. J.; Plazas, A. A.; Romer, A. K.; Roodman, A.; Rykoff, E. S.; Scarpine, V.; Schubnell, M.; Smith, R. C.; Soares-Santos, M.; Sobreira, F.; Tarle, G.; Thomas, D.; Walker, A. R.; Wester, W.; DES Collaboration

    2018-05-01

    In this paper, the effect of weak lensing magnification on galaxy number counts is studied by cross-correlating the positions of two galaxy samples, separated by redshift, using the Dark Energy Survey Science Verification data set. This analysis is carried out for galaxies that are selected only by its photometric redshift. An extensive analysis of the systematic effects, using new methods based on simulations is performed, including a Monte Carlo sampling of the selection function of the survey.

  10. Multistep Resistance Selection and Postantibiotic-Effect Studies of the Antipneumococcal Activity of LBM415 Compared to Other Agents▿

    PubMed Central

    Kosowska-Shick, Klaudia; Credito, Kim L.; Pankuch, Glenn A.; DeWasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

    2007-01-01

    LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h. PMID:17116666

  11. Multistep resistance selection and postantibiotic-effect studies of the antipneumococcal activity of LBM415 compared to other agents.

    PubMed

    Kosowska-Shick, Klaudia; Credito, Kim L; Pankuch, Glenn A; DeWasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C

    2007-02-01

    LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h.

  12. Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells

    PubMed Central

    Fink, Brian D.; O'Malley, Yunxia; Dake, Brian L.; Ross, Nicolette C.; Prisinzano, Thomas E.; Sivitz, William I.

    2009-01-01

    Background Previously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and Results To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. Conclusions In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level. PMID:19158951

  13. Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in endothelial cells.

    PubMed

    Fink, Brian D; O'Malley, Yunxia; Dake, Brian L; Ross, Nicolette C; Prisinzano, Thomas E; Sivitz, William I

    2009-01-01

    Previously, we reported that the "antioxidant" compound "mitoQ" (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level.

  14. Influence of culture on contraceptive utilization among HIV-positive women in Brazil, Kenya, and South Africa.

    PubMed

    Todd, Catherine S; Stibich, Mark A; Laher, Fatima; Malta, Monica S; Bastos, Francisco I; Imbuki, Kennedy; Shaffer, Douglas N; Sinei, Samuel K; Gray, Glenda E

    2011-02-01

    Contraceptive choice and discontinuation are poorly understood among HIV-positive women, and HIV disease and culture may influence decisions. We assessed factors influencing contraceptive decision-making among HIV-positive women in three countries. This qualitative assessment of 108 HIV-positive women (36/site, selected by age and parity strata) was conducted in Rio de Janeiro, Brazil; Kericho, Kenya; and Soweto, South Africa. Freelist interviews assessed knowledge and attitudes towards contraception and were analyzed enumerating frequency and saliency of mentions. There was intersite consensus around list items but priority and themes varied. Site-specific factors influencing contraceptive choice were male partner wishes and fertility desire (Brazil), side-effects (South Africa), and impact on health and HIV progression (Kenya). Age, parity, and taking antiretroviral therapy (ART) impacted some themes. Contraceptive use among HIV-positive women is substantially influenced by culture and other factors. Counseling efforts should consider individual factors in method selection and offer method variety to accommodate changing needs.

  15. The effect of genetic selection for Johne's disease resistance in dairy cattle: Results of a genetic-epidemiological model.

    PubMed

    van Hulzen, K J E; Koets, A P; Nielen, M; Heuven, H C M; van Arendonk, J A M; Klinkenberg, D

    2014-03-01

    The objective of this study was to model genetic selection for Johne's disease resistance and to study the effect of different selection strategies on the prevalence in the dairy cattle population. In the Netherlands, a certification-and-surveillance program is in use to reduce prevalence and presence of sources of infection in milk by culling ELISA-positive dairy cows in infected herds. To investigate the additional genetic effect of this program, a genetic-epidemiological model was developed to assess the effect of selection of cows that test negative for Johne's disease (dam selection). The genetic effect of selection at the sire level was also considered (sire selection), assuming selection of 80% of sires producing the most resistant offspring based on their breeding values, as well as the combined effect. Parameters assumed to be affected by genetic selection were the length of the latent period, susceptibility (i.e., the number of infectious doses needed to become infected), or the length of susceptible period as a calf. The effect of selection was measured by the time in years required to eliminate infection. Sensitivity analysis was performed for heritability, accuracy of selection, and intensity of selection. For dam selection, responses to selection were small, requiring 379 to 702 yr for elimination. For sire selection, responses were much larger, although elimination still required 147 to 223 yr. The response to selection was largest if genetic selection affected the length of the susceptible period, followed by the susceptibility, and finally the length of the latent period. Genetic selection for Johne's disease resistance by certification and surveillance is too slow for practical purpose, but that selection on the sire level is able to contribute to the control of Johne's disease in the long run. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Exploiting persistent infection for selection of bovine herpesvirus 4 recombinants.

    PubMed

    Donofrio, G; Martignani, E; Cavirani, S; Flammini, C F

    2005-09-01

    Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus with no clear disease association, and due to its biological characteristics, has been suggested as a gene delivery vector. It was demonstrated previously that recombinant BoHV-4 carrying a neomycin-resistance gene was able to infect a human rhabdomyosarcoma cell line (RD-4), resulting in no detectable cytopathic effect (CPE) and allowing selection of G418-resistant persistently-infected cells containing circular episomal viral DNA [Donofrio, G., Cavirani, S., van Santen, V.L., 2000a. Establishment of a cell line persistently infected with recombinant BoHV-4. J. Gen. Virol. 81, 1807-1814.]. Those cells produce infectious virus and infection is predominantly non-permissive and non-cytopathic. Starting from these results, the ability of RD-4 cells to sustain persistent infection was combined with positive selection activity conferred by the neomycin-expression cassette insert, as an easier way to select recombinants of BoHV-4 following homologous recombination in permissive cells. A tool for selecting BoHV-4 recombinants was developed by drug positive selection.

  17. Positive selection on D-lactate dehydrogenases of Lactobacillus delbrueckii subspecies bulgaricus.

    PubMed

    Zhang, Jifeng; Gong, Guangyu; Wang, Xiao; Zhang, Hao; Tian, Weidong

    2015-08-01

    Lactobacillus delbrueckii has been widely used for yogurt fermentation. It has genes encoding both D- and L-type lactate dehydrogenases (LDHs) that catalyse the production of L(+) or D(-) stereoisomer of lactic acid. D-lactic acid is the primary lactate product by L. delbrueckii, yet it cannot be metabolised by human intestine. Since it has been domesticated for long time, an interesting question arises regarding to whether the selection pressure has affected the evolution of both L-LDH and D-LDH genes in the genome. To answer this question, in this study the authors first investigated the evolution of these two genes by constructing phylogenetic trees. They found that D-LDH-based phylogenetic tree could better represent the phylogenetic relationship in the acidophilus complex than L-LDH-based tree. They next investigated the evolutions of LDH genes of L. delbrueckii at amino acid level, and found that D-LDH gene in L. delbrueckii is positively selected, possibly a consequence of long-term domestication. They further identified four amino acids that are under positive selection. One of them, V261, is located at the centre of three catalytic active sites, indicating likely functional effects on the enzyme activity. The selection from the domestication process thus provides direction for future engineering of D-LDH.

  18. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes.

    PubMed

    Dasmeh, Pouria; Kepp, Kasper P

    2017-08-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of -6 at physiological pH, whereas the closely related gibbons and macaques have -3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.

  19. 5 CFR 2638.202 - Responsibilities of agency head.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and shall exercise personal leadership in establishing, maintaining, and carrying out the agency's... program in a positive and effective manner. (b) Selection of a designated agency ethics official. The head...

  20. Adjustable small-incision selective tenotomy and plication for correction of incomitant vertical strabismus and torsion

    PubMed Central

    Chang, Melinda Y.; Pineles, Stacy L.; Velez, Federico G.

    2015-01-01

    PURPOSE To evaluate the effectiveness of adjustable small-incision selective tenotomy and plication of vertical rectus muscles in correcting vertical strabismus incomitant in horizontal gaze positions and cyclotorsion. METHODS The medical records of all patients who underwent adjustable small-incision selective tenotomy or plication of a vertical rectus muscle for correction of horizontally incomitant vertical strabismus or cyclotorsion by a single surgeon at a single eye institute from July 2013 to September 2014 were retrospectively reviewed. Selective tenotomy and plication were performed on either the nasal or temporal side of vertical rectus muscles, based on the direction of cyclotorsion and incomitance of vertical strabismus. RESULTS Of 9 patients identified, 8 (89%) had successful correction of horizontally incomitant vertical strabismus, with postoperative vertical alignment within 4Δ of orthotropia in primary position, lateral gazes, and downgaze. Of the 8 patients with preoperative cyclotorsion, 4 (50%) were successfully corrected, with <5° of cyclotorsion postoperatively. Of the 4 patients in whom cyclotorsion did not improve, 3 had undergone prior strabismus surgery, and 2 had restrictive strabismus. Eight of the 9 patients (89%) reported postoperative resolution of diplopia. CONCLUSIONS Adjustable small-incision selective tenotomy and plication effectively treat horizontally incomitant vertical strabismus. These surgeries may be less effective for correcting cyclotorsion in patients with restriction or prior strabismus surgery. Advantages are that they may be performed in an adjustable manner and, in some cases, under topical anesthesia. PMID:26486021

  1. Occipital Alpha and Gamma Oscillations Support Complementary Mechanisms for Processing Stimulus Value Associations.

    PubMed

    Marshall, Tom R; den Boer, Sebastiaan; Cools, Roshan; Jensen, Ole; Fallon, Sean James; Zumer, Johanna M

    2018-01-01

    Selective attention is reflected neurally in changes in the power of posterior neural oscillations in the alpha (8-12 Hz) and gamma (40-100 Hz) bands. Although a neural mechanism that allows relevant information to be selectively processed has its advantages, it may lead to lucrative or dangerous information going unnoticed. Neural systems are also in place for processing rewarding and punishing information. Here, we examine the interaction between selective attention (left vs. right) and stimulus's learned value associations (neutral, punished, or rewarded) and how they compete for control of posterior neural oscillations. We found that both attention and stimulus-value associations influenced neural oscillations. Whereas selective attention had comparable effects on alpha and gamma oscillations, value associations had dissociable effects on these neural markers of attention. Salient targets (associated with positive and negative outcomes) hijacked changes in alpha power-increasing hemispheric alpha lateralization when salient targets were attended, decreasing it when they were being ignored. In contrast, hemispheric gamma-band lateralization was specifically abolished by negative distractors. Source analysis indicated occipital generators of both attentional and value effects. Thus, posterior cortical oscillations support both the ability to selectively attend while at the same time retaining the ability to remain sensitive to valuable features in the environment. Moreover, the versatility of our attentional system to respond separately to salient from merely positively valued stimuli appears to be carried out by separate neural processes reflected in different frequency bands.

  2. Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

    PubMed

    Galloway, Claire R; Lebois, Evan P; Shagarabi, Shezza L; Hernandez, Norma A; Manns, Joseph R

    2014-01-01

    Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

  3. Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

    2015-06-01

    Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

  4. Does Learning or Instinct Shape Habitat Selection?

    PubMed Central

    Nielsen, Scott E.; Shafer, Aaron B. A.; Boyce, Mark S.; Stenhouse, Gordon B.

    2013-01-01

    Habitat selection is an important behavioural process widely studied for its population-level effects. Models of habitat selection are, however, often fit without a mechanistic consideration. Here, we investigated whether patterns in habitat selection result from instinct or learning for a population of grizzly bears (Ursus arctos) in Alberta, Canada. We found that habitat selection and relatedness were positively correlated in female bears during the fall season, with a trend in the spring, but not during any season for males. This suggests that habitat selection is a learned behaviour because males do not participate in parental care: a genetically predetermined behaviour (instinct) would have resulted in habitat selection and relatedness correlations for both sexes. Geographic distance and home range overlap among animals did not alter correlations indicating that dispersal and spatial autocorrelation had little effect on the observed trends. These results suggest that habitat selection in grizzly bears are partly learned from their mothers, which could have implications for the translocation of wildlife to novel environments. PMID:23341983

  5. Does learning or instinct shape habitat selection?

    PubMed

    Nielsen, Scott E; Shafer, Aaron B A; Boyce, Mark S; Stenhouse, Gordon B

    2013-01-01

    Habitat selection is an important behavioural process widely studied for its population-level effects. Models of habitat selection are, however, often fit without a mechanistic consideration. Here, we investigated whether patterns in habitat selection result from instinct or learning for a population of grizzly bears (Ursus arctos) in Alberta, Canada. We found that habitat selection and relatedness were positively correlated in female bears during the fall season, with a trend in the spring, but not during any season for males. This suggests that habitat selection is a learned behaviour because males do not participate in parental care: a genetically predetermined behaviour (instinct) would have resulted in habitat selection and relatedness correlations for both sexes. Geographic distance and home range overlap among animals did not alter correlations indicating that dispersal and spatial autocorrelation had little effect on the observed trends. These results suggest that habitat selection in grizzly bears are partly learned from their mothers, which could have implications for the translocation of wildlife to novel environments.

  6. Weighted Geometric Dilution of Precision Calculations with Matrix Multiplication

    PubMed Central

    Chen, Chien-Sheng

    2015-01-01

    To enhance the performance of location estimation in wireless positioning systems, the geometric dilution of precision (GDOP) is widely used as a criterion for selecting measurement units. Since GDOP represents the geometric effect on the relationship between measurement error and positioning determination error, the smallest GDOP of the measurement unit subset is usually chosen for positioning. The conventional GDOP calculation using matrix inversion method requires many operations. Because more and more measurement units can be chosen nowadays, an efficient calculation should be designed to decrease the complexity. Since the performance of each measurement unit is different, the weighted GDOP (WGDOP), instead of GDOP, is used to select the measurement units to improve the accuracy of location. To calculate WGDOP effectively and efficiently, the closed-form solution for WGDOP calculation is proposed when more than four measurements are available. In this paper, an efficient WGDOP calculation method applying matrix multiplication that is easy for hardware implementation is proposed. In addition, the proposed method can be used when more than exactly four measurements are available. Even when using all-in-view method for positioning, the proposed method still can reduce the computational overhead. The proposed WGDOP methods with less computation are compatible with global positioning system (GPS), wireless sensor networks (WSN) and cellular communication systems. PMID:25569755

  7. Lateral decubitus position vs. lithotomy position: which is the best way to minimize patient's pain perception during transrectal prostate biopsy?

    PubMed

    Song, Phil Hyun; Ko, Young Hwii

    2017-01-01

    Considering the distinctive nature in terms of psychological stress and anal tone of position which is generally selected between lithotomy and left lateral decubitus (LLD), we postulated its effect on pain perception during biopsy, and investigated their association. A prospective study for comparison of two biopsy positions which were perform in a different working day was conducted for 208 men (lithotomy position=86, LLD=122). The decision on the position was made solely based on the patient's preference for the biopsy day, and all procedures were performed according to the identical protocol (12-core biopsy with intrarectal lidocaine gel), probe, and needle. The maximal degree of pain during the entire process was assessed using a visual analogue scale (VAS), immediately after biopsy. After propensity matching, a total of 152 patients were finally selected (lithotomy group=76, LLD=76), then peri-biopsy parameters were compared. Between groups, no differences were observed across all variables including age, obesity, prostate volume, serum PSA, international prostate symptom score, and cancer detection rate, except mean (±standard deviation) VAS score (3.89±2.01 vs. 4.58±2.22, p=0.049). VAS score showed significant association solely with patient's position (Pearson's coefficient=-0.165, p=0.042). In multiple linear regression models regarding the effect of clinical variables on VAS score, patient position was a single independent predictor favoring lithotomy position to decrease perceived pain (B=-0.928, p=0.024). These data suggest lithotomy position as a proper way to perform transrectal prostate biopsy with routine use of topical lidocaine gel in comparison with conventional LLD position. Copyright® by the International Brazilian Journal of Urology.

  8. Towards functional selectivity for α6β3γ2 GABAA receptors: a series of novel pyrazoloquinolinones

    PubMed Central

    Treven, Marco; Siebert, David C B; Holzinger, Raphael; Bampali, Konstantina; Fabjan, Jure; Varagic, Zdravko; Wimmer, Laurin; Steudle, Friederike; Scholze, Petra; Schnürch, Michael; Mihovilovic, Marko D

    2017-01-01

    Background and Purpose The GABAA receptors are ligand‐gated ion channels, which play an important role in neurotransmission. Their variety of binding sites serves as an appealing target for many clinically relevant drugs. Here, we explored the functional selectivity of modulatory effects at specific extracellular α+/β− interfaces, using a systematically varied series of pyrazoloquinolinones. Experimental Approach Recombinant GABAA receptors were expressed in Xenopus laevis oocytes and modulatory effects on GABA‐elicited currents by the newly synthesized and reference compounds were investigated by the two‐electrode voltage clamp method. Key Results We identified a new compound which, to the best of our knowledge, shows the highest functional selectivity for positive modulation at α6β3γ2 GABAA receptors with nearly no residual activity at the other αxβ3γ2 (x = 1–5) subtypes. This modulation was independent of affinity for α+/γ− interfaces. Furthermore, we demonstrated for the first time a compound that elicits a negative modulation at specific extracellular α+/β− interfaces. Conclusion and Implications These results constitute a major step towards a potential selective positive modulation of certain α6‐containing GABAA receptors, which might be useful to elicit their physiological role. Furthermore, these studies pave the way towards insights into molecular principles that drive positive versus negative allosteric modulation of specific GABAA receptor isoforms. PMID:29127702

  9. 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.

  10. Effective motion planning strategy for space robot capturing targets under consideration of the berth position

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Liu, Jinguo

    2018-07-01

    Although many motion planning strategies for missions involving space robots capturing floating targets can be found in the literature, relatively little has discussed how to select the berth position where the spacecraft base hovers. In fact, the berth position is a flexible and controllable factor, and selecting a suitable berth position has a great impact on improving the efficiency of motion planning in the capture mission. Therefore, to make full use of the manoeuvrability of the space robot, this paper proposes a new viewpoint that utilizes the base berth position as an optimizable parameter to formulate a more comprehensive and effective motion planning strategy. Considering the dynamic coupling, the dynamic singularities, and the physical limitations of space robots, a unified motion planning framework based on the forward kinematics and parameter optimization technique is developed to convert the planning problem into the parameter optimization problem. For getting rid of the strict grasping position constraints in the capture mission, a new conception of grasping area is proposed to greatly simplify the difficulty of the motion planning. Furthermore, by utilizing the penalty function method, a new concise objective function is constructed. Here, the intelligent algorithm, Particle Swarm Optimization (PSO), is worked as solver to determine the free parameters. Two capturing cases, i.e., capturing a two-dimensional (2D) planar target and capturing a three-dimensional (3D) spatial target, are studied under this framework. The corresponding simulation results demonstrate that the proposed method is more efficient and effective for planning the capture missions.

  11. Effects of the sitting position on the body posture of children aged 11 to 13 years.

    PubMed

    Drza-Grabiec, Justyna; Snela, Sławomir; Rykała, Justyna; Podgórska, Justyna; Rachwal, Maciej

    2015-01-01

    Nowadays, children spend increasingly more time in a seated position, both at school during class and at home in front of a computer or television. The aim of this study was to compare selected parameters describing body posture and scoliosis among children in sitting and standing positions. It was an observational, cross-sectional study involving 91 primary school children aged 11-13 years. The children's backs were photographed in standing and sitting positions. The values of selected parameters were calculated using photogrammetric examination based on the Moire projection phenomenon. The results show significant statistical differences for the parameters defining the anteroposterior curves of the spine. The sitting position resulted in a decreased angle of inclination of the thoracolumbar spine, reduced depths of thoracic kyphosis and lumbar lordosis, and pelvic asymmetry. Maintaining a sitting position for a long time results in advanced asymmetries of the trunk and scoliosis, and causes a decrease in lumbar lordosis and kyphosis of a child's entire spine. Therefore, we advocate the introduction of posture education programs for schoolchildren.

  12. Sensitive and selective culture medium for detection of environmental Clostridium difficile isolates without requirement for anaerobic culture conditions.

    PubMed

    Cadnum, Jennifer L; Hurless, Kelly N; Deshpande, Abhishek; Nerandzic, Michelle M; Kundrapu, Sirisha; Donskey, Curtis J

    2014-09-01

    Effective and easy-to-use methods for detecting Clostridium difficile spore contamination would be useful for identifying environmental reservoirs and monitoring the effectiveness of room disinfection. Culture-based detection methods are sensitive for detecting C. difficile, but their utility is limited due to the requirement of anaerobic culture conditions and microbiological expertise. We developed a low-cost selective broth medium containing thioglycolic acid and l-cystine, termed C. difficile brucella broth with thioglycolic acid and l-cystine (CDBB-TC), for the detection of C. difficile from environmental specimens under aerobic culture conditions. The sensitivity and specificity of CDBB-TC (under aerobic culture conditions) were compared to those of CDBB (under anaerobic culture conditions) for the recovery of C. difficile from swabs collected from hospital room surfaces. CDBB-TC was significantly more sensitive than CDBB for recovering environmental C. difficile (36/41 [88%] versus 21/41 [51%], respectively; P = 0.006). C. difficile latex agglutination, an enzyme immunoassay for toxins A and B or glutamate dehydrogenase, and a PCR for toxin B genes were all effective as confirmatory tests. For 477 total environmental cultures, the specificity of CDBB-TC versus that of CDBB based upon false-positive yellow-color development of the medium without recovery of C. difficile was 100% (0 false-positive results) versus 96% (18 false-positive results), respectively. False-positive cultures for CDBB were attributable to the growth of anaerobic non-C. difficile organisms that did not grow in CDBB-TC. Our results suggest that CDBB-TC provides a sensitive and selective medium for the recovery of C. difficile organisms from environmental samples, without the need for anaerobic culture conditions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Context-specific control and the Stroop negative priming effect.

    PubMed

    Milliken, Bruce; Thomson, David R; Bleile, Karmen; MacLellan, Ellen; Giammarco, Maria

    2012-01-01

    The present study highlights the utility of context-specific learning for different probe types in accounting for the commonly observed dependence of negative priming on probe selection. Using a Stroop priming procedure, Experiments 1a and 1b offered a demonstration that Stroop priming effects can differ qualitatively for selection and no-selection probes when probe selection is manipulated between subjects, but not when it is manipulated randomly from trial to trial within subject (see also Moore, 1994). In Experiments 2 and 3, selection and no-selection probes served as two contexts that varied randomly from trial to trial, but for which proportion repeated was manipulated separately. A context-specific proportion repeated effect was observed in Experiment 2, characterized by modest quantitative shifts in the repetition effects as a function of the context-specific proportion repeated manipulation. However, with a longer intertrial interval in Experiment 3, a context-specific proportion repeated manipulation that focused on the no-selection probes changed the repetition effect qualitatively, from negative priming when the proportion repeated was .25 to positive priming when the proportion repeated was .75. The results are discussed with reference to the role of rapid, context-specific learning processes in the integration of prior experiences with current perception and action.

  14. Implications of Information and Communication Technologies (ICT) for School-Home Communication

    ERIC Educational Resources Information Center

    Heath, Don; Maghrabi, Rozan; Carr, Nora

    2015-01-01

    Research demonstrates the positive impact of parental involvement on students, families and schools. Studies also indicate a close connection between effective school-home communication and increased parental involvement and engagement in learning. Effective selection and use of Information Communication Technologies (ICT) invites more effective…

  15. Advocating for Grade-Based Acceleration

    ERIC Educational Resources Information Center

    Guilbault, Keri M.

    2014-01-01

    Parents often struggle with the decision to accelerate their child and may worry about social and emotional issues, although research indicates positive effects on the social and emotional adjustment of carefully selected accelerants. As children's advocates, parents can work effectively with a school system to secure an appropriate academic…

  16. Tunable Infrared Semiconductor Lasers

    DTIC Science & Technology

    2013-12-20

    stripe to different positions of an addressable chirped, location-dependent period grating to select the different lasing wavelengths. Interferometric...grating or vernier effects. Our tuning mechanism is to shift the pump stripe to different positions of an addressable chirped, location-dependent period... stripe is applied and the lateral direction is the perpendicular direction across the pump stripe and parallel to the grating lines.  The chirped

  17. Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor β agonists.

    PubMed

    Burkholder, Timothy P; Cunningham, Brian E; Clayton, Joshua R; Lander, Peter A; Brown, Matthew L; Doti, Robert A; Durst, Gregory L; Montrose-Rafizadeh, Chahrzad; King, Constance; Osborne, Harold E; Amos, Robert M; Zink, Richard W; Stramm, Lawrence E; Burris, Thomas P; Cardona, Guemalli; Konkol, Debra L; Reidy, Charles; Christe, Michael E; Genin, Michael J

    2015-04-01

    The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Mutation-profile-based methods for understanding selection forces in cancer somatic mutations: a comparative analysis.

    PubMed

    Zhou, Zhan; Zou, Yangyun; Liu, Gangbiao; Zhou, Jingqi; Wu, Jingcheng; Zhao, Shimin; Su, Zhixi; Gu, Xun

    2017-08-29

    Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes ( C N / C S ) and normal populations ( p N / p S ). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels. Both the relaxation of purifying selection on passenger mutations and the positive selection of driver mutations may contribute to the increased C N / C S values of human genes in cancer genomes compared with the p N / p S values in human populations. The C N / C S values also contribute to the improved classification of cancer genes and a better understanding of the onco-functionalization of cancer genes during oncogenesis. The use of our computational pipeline to identify cancer-specific positively and negatively selected genes may provide useful information for understanding the evolution of cancers and identifying possible targets for therapeutic intervention.

  19. Field investigation of influenza vaccine effectiveness on morbidity.

    PubMed

    Carrat, F; Tachet, A; Rouzioux, C; Housset, B; Valleron, A J

    1998-01-01

    Our objective was to evaluate influenza vaccine effectiveness during an influenza epidemic by means of a matched case-control study. The study was performed by 35 general practitioners who collected specimens for influenza virus testing from 610 patients who consulted for infectious syndrome: 168 (28%) were influenza-positive. Two designs were used for selecting controls to take into account the high incidence-rate of influenza-like illness and the various possible protective effects of the vaccine. A first disease-free control matched for age and sex was selected during the same week as the case. A second control matched for age and sex was selected at the end of the epidemic period, irrespective of disease history during the epidemic period. Upper and lower bounds of vaccine effectiveness can be derived from these case-control designs. After adjustment for chronic conditions and exposure to an index case, analysis of the matched-pairs whose case was influenza-positive showed, with the first group of controls, an influenza vaccine effectiveness of 68% (95% CI, 10% to 88%) and, in the second group, 53% (95% CI, -19% to 82%). Among the pairs whose case was negative for influenza, vaccine effectiveness was, respectively, 31% (95% CI, -17% to 59%) and 12% (95% CI, -47% to 47%). Vaccine effectiveness was highest for the H3N2 subtype whose vaccine strain was identical to that of the wild-type strain. The results suggest that influenza vaccine is effective in the field in preventing influenza morbidity.

  20. The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors

    PubMed Central

    Chatzidaki, Anna; D'Oyley, Jarryl M.; Gill-Thind, JasKiran K.; Sheppard, Tom D.; Millar, Neil S.

    2015-01-01

    Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9′ position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22′ position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. PMID:25998276

  1. The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.

    PubMed

    Chatzidaki, Anna; D'Oyley, Jarryl M; Gill-Thind, JasKiran K; Sheppard, Tom D; Millar, Neil S

    2015-10-01

    Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9' position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22' position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

    PubMed

    Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

    2013-12-01

    Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

  3. A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing.

    PubMed

    Stiffler, Michael A; Subramanian, Subu K; Salinas, Victor H; Ranganathan, Rama

    2016-07-03

    Site-directed mutagenesis has long been used as a method to interrogate protein structure, function and evolution. Recent advances in massively-parallel sequencing technology have opened up the possibility of assessing the functional or fitness effects of large numbers of mutations simultaneously. Here, we present a protocol for experimentally determining the effects of all possible single amino acid mutations in a protein of interest utilizing high-throughput sequencing technology, using the 263 amino acid antibiotic resistance enzyme TEM-1 β-lactamase as an example. In this approach, a whole-protein saturation mutagenesis library is constructed by site-directed mutagenic PCR, randomizing each position individually to all possible amino acids. The library is then transformed into bacteria, and selected for the ability to confer resistance to β-lactam antibiotics. The fitness effect of each mutation is then determined by deep sequencing of the library before and after selection. Importantly, this protocol introduces methods which maximize sequencing read depth and permit the simultaneous selection of the entire mutation library, by mixing adjacent positions into groups of length accommodated by high-throughput sequencing read length and utilizing orthogonal primers to barcode each group. Representative results using this protocol are provided by assessing the fitness effects of all single amino acid mutations in TEM-1 at a clinically relevant dosage of ampicillin. The method should be easily extendable to other proteins for which a high-throughput selection assay is in place.

  4. 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.

  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. 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.

  8. A Comparative Study to Evaluate the Effect of Crook Lying Position versus Sitting Position on Forced Vital Capacity (FVC) in Healthy Individuals.

    PubMed

    Sudan, Dharampal Singh; Singh, Harvinder

    2014-02-01

    To prove the effect of body position on the Forced Vital Capacity (FVC) and to find out the better position amongst the sitting and crook lying position as both are considered to be the best respiratory positions as far as FVC is concerned, but no research work is done to find out the better amongst the two. We analyzed the FVC of the randomly selected 100 subjects (both males and females) in sitting and crook lying position respectively. Computerized Pulmonary Function Testing (PFT) apparatus was used for analysis where three readings of FVC were taken in each position from which best ones were taken for analysis. Mean FVC in crook lying position was found out to be 88.83% as compared to 99.07% in sitting position showing a difference of 10.24 %. The values were analyzed by using standard t-test which gave t-value 18.4316 and p-value 0.0001 which is statistically significant. The results show that FVC was more in sitting position as compared to crook lying position.

  9. Evidence for the impact of quality improvement collaboratives: systematic review

    PubMed Central

    2008-01-01

    Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care. Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases. Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes. Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect. Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives. PMID:18577559

  10. Constraints on arm selection processes when reaching: degrees of freedom and joint amplitudes interact to influence limb selection.

    PubMed

    Kim, Wondae; Buchanan, John; Gabbard, Carl

    2011-01-01

    With an interest in identifying the variables that constrain arm choice when reaching, the authors had 11 right-handed participants perform free-choice and assigned-limb reaches at 9 object positions. The right arm was freely selected 100% of the time when reaching to positions at 30° and 40° into right hemispace. However, the left arm was freely selected to reach to positions at -30° and -40° in left hemispace 85% of the time. A comparison between free- and assigned-limb reaching kinematics revealed that free limb selection when reaching to the farthest positions was constrained by joint amplitude requirements and the time devoted to limb deceleration. Differences between free- and assigned-arm reaches were not evident when reaching to the midline and positions of ±10°, even though the right arm was freely selected most often for these positions. Different factors contribute to limb selection as a function of distance into a specific hemispace.

  11. The effects of a regional natural history course on outcome expectancy, self-efficacy, and instructional methods of science teachers

    NASA Astrophysics Data System (ADS)

    Dechant, Thomas Fredrick

    Recent concerns about the effectiveness of science instruction have prompted a variety of strategies and research to effect positive changes. Research has indicated that among the contributing factors to the success of students learning science are teacher outcome expectancy, self-efficacy, and the selection and use of various teaching methods. Inservice training opportunities for public school teachers have been proposed as a strategy that can yield positive changes in these areas. Environmental education has also been proposed as a viable component of teaching science, but focus on global, and the omission of local themes is common. This study assessed the effects of an inservice training course entitled "Natural History of the Southern Appalachians" on regional teachers' outcome expectancy, self-efficacy, and science teaching methods. Through the administration of the Science Teaching Efficacy Belief Instrument and the Science Teaching Strategies Survey before taking the course and after taking the course, changes in the teachers outcome expectancy (p<.05), self-efficacy (p<.10), and teaching strategy selection were measured. In all three areas, desired positive changes have resulted from teachers completing the course. It appears that regionally specific Natural History training gives teachers inexpensive options to teach science, as well as making them more comfortable with the delivery of science instruction.

  12. Modified clay minerals efficiency against chemical and biological warfare agents for civil human protection.

    PubMed

    Plachá, Daniela; Rosenbergová, Kateřina; Slabotínský, Jiří; Kutláková, Kateřina Mamulová; Studentová, Soňa; Martynková, Gražyna Simha

    2014-04-30

    Sorption efficiencies of modified montmorillonite and vermiculite of their mono ionic Na and organic HDTMA and HDP forms were studied against chemical and biological warfare agents such as yperite and selected bacterial strains. Yperite interactions with modified clay minerals were observed through its capture in low-density polyethylene foil-modified clay composites by measuring yperite gas permeation with using chemical indication and gas chromatography methods. The antibacterial activities of synthetized organoclays were tested against selected Gram-positive and Gram-negative bacterial species in minimum inhibitory concentration tests. The obtained results showed a positive influence of modified clay minerals on the significant yperite breakthrough-time increase. The most effective material was the polyethylene-Na form montmorillonite, while the polyethylene-Na form vermiculite showed the lowest efficiency. With increasing organic cations loading in the interlayer space the montmorillonite efficiency decreased, and in the case of vermiculite an opposite effect was observed. Generally the modified montmorillonites were more effective than modified vermiculites. The HDP cations seem to be more effective compare to the HDTMA. The antibacterial activity tests confirmed efficiency of all organically modified clay minerals against Gram-positive bacteria. The confirmation of antibacterial activity against Y. pestis, plague bacteria, is the most interesting result of this part of the study. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    PubMed

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  14. Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

    PubMed

    Kasten, Chelsea R; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L

    2018-05-01

    Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.

  15. 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.

  16. Positive selection on sociobiological traits in invasive fire ants.

    PubMed

    Privman, Eyal; Cohen, Pnina; Cohanim, Amir B; Riba-Grognuz, Oksana; Shoemaker, DeWayne; Keller, Laurent

    2018-06-19

    The fire ant Solenopsis invicta and its close relatives are highly invasive. Enhanced social cooperation may facilitate invasiveness in these and other invasive ant species. We investigated whether invasiveness in Solenopsis fire ants was accompanied by positive selection on sociobiological traits by applying a phylogenomics approach to infer ancient selection, and a population genomics approach to infer recent and ongoing selection in both native and introduced S. invicta populations. A combination of whole-genome sequencing of 40 haploid males and reduced-representation genomic sequencing of 112 diploid workers identified 1,758,116 and 169,682 polymorphic markers, respectively. The resulting high-resolution maps of genomic polymorphism provide high inference power to test for positive selection. Our analyses provide evidence of positive selection on putative ion channel genes, which are implicated in neurological functions, and on vitellogenin, which is a key regulator of development and caste determination. Furthermore, molecular functions implicated in pheromonal signaling have experienced recent positive selection. Genes with signatures of positive selection were significantly more often those over-expressed in workers compared with queens and males, suggesting that worker traits are under stronger selection than queen and male traits. These results provide insights into selection pressures and ongoing adaptation in an invasive social insect and support the hypothesis that sociobiological traits are under more positive selection than traits related to non-social traits in such invasive species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Correlation of Local Effects of DNA Sequence and Position of Beta-Alanine Inserts with Polyamide-DNA Complex Binding Affinities and Kinetics

    PubMed Central

    Wang, Shuo; Nanjunda, Rupesh; Aston, Karl; Bashkin, James K.; Wilson, W. David

    2012-01-01

    In order to better understand the effects of β-alanine (β) substitution and the number of heterocycles on DNA binding affinity and selectivity, the interactions of an eight-ring hairpin polyamide (PA) and two β derivatives as well as a six-heterocycle analog have been investigated with their cognate DNA sequence, 5′-TGGCTT-3′. Binding selectivity and the effects of β have been investigated with the cognate and five mutant DNAs. A set of powerful and complementary methods have been employed for both energetic and structural evaluations: UV-melting, biosensor-surface plasmon resonance, isothermal titration calorimetry, circular dichroism and a DNA ligation ladder global structure assay. The reduced number of heterocycles in the six-ring PA weakens the binding affinity; however, the smaller PA aggregates significantly less than the larger PAs, and allows us to obtain the binding thermodynamics. The PA-DNA binding enthalpy is large and negative with a large negative ΔCp, and is the primary driving component of the Gibbs free energy. The complete SPR binding results clearly show that β substitutions can substantially weaken the binding affinity of hairpin PAs in a position-dependent manner. More importantly, the changes in PA binding to the mutant DNAs further confirm the position-dependent effects on PA-DNA interaction affinity. Comparison of mutant DNA sequences also shows a different effect in recognition of T•A versus A•T base pairs. The effects of DNA mutations on binding of a single PA as well as the effects of the position of β substitution on binding tell a clear and very important story about sequence dependent binding of PAs to DNA. PMID:23167504

  18. A Theory-Based Career Development Course: A Plant in the Garden.

    ERIC Educational Resources Information Center

    Mackin, R. Kevin; Hansen, L. Sunny

    1981-01-01

    An evaluation of the effectiveness of a career development class for high school students supports the viability of career development curricula as part of a comprehensive career guidance program. The class had a positive effect on students' career maturity and skills in self-appraisal and goal selection. (JAC)

  19. Effectiveness of the Sexual Attitude Restructuring Curriculum amongst Taiwanese Graduate Students

    ERIC Educational Resources Information Center

    Lin, Yi-Li; Lin, Yen-Chin

    2018-01-01

    This article discusses the effectiveness of the Sexual Attitude Restructuring (SAR) curriculum in developing positive sexual attitudes amongst Taiwanese graduate students in human sexuality. Through purposive sampling, 32 graduate students in human sexuality were selected to participate in the study. Before and after providing participants with a…

  20. Alternative Work Schedules: Two Field Quasi-Experiments.

    ERIC Educational Resources Information Center

    Dunham, Randall B.; And Others

    1987-01-01

    Changed trial group employees from a 5/40 to a 4/40 work schedule for four months then returned to a 5/40 schedule. In a second study, changed trial group employees from 5/40 to flextime. Organizational effectiveness was selectively enhanced. The most powerful effect was on worker attitudes. A mild positive effect was evident for several general…

  1. p-hacking by post hoc selection with multiple opportunities: Detectability by skewness test?: Comment on Simonsohn, Nelson, and Simmons (2014).

    PubMed

    Ulrich, Rolf; Miller, Jeff

    2015-12-01

    Simonsohn, Nelson, and Simmons (2014) have suggested a novel test to detect p-hacking in research, that is, when researchers report excessive rates of "significant effects" that are truly false positives. Although this test is very useful for identifying true effects in some cases, it fails to identify false positives in several situations when researchers conduct multiple statistical tests (e.g., reporting the most significant result). In these cases, p-curves are right-skewed, thereby mimicking the existence of real effects even if no effect is actually present. (c) 2015 APA, all rights reserved).

  2. Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure.

    PubMed

    Bjornsdottir, Erla; Keenan, Brendan T; Eysteinsdottir, Bjorg; Arnardottir, Erna Sif; Janson, Christer; Gislason, Thorarinn; Sigurdsson, Jon Fridrik; Kuna, Samuel T; Pack, Allan I; Benediktsdottir, Bryndis

    2015-06-01

    Obstructive sleep apnea leads to recurrent arousals from sleep, oxygen desaturations, daytime sleepiness and fatigue. This can have an adverse impact on quality of life. The aims of this study were to compare: (i) quality of life between the general population and untreated patients with obstructive sleep apnea; and (ii) changes of quality of life among patients with obstructive sleep apnea after 2 years of positive airway pressure treatment between adherent patients and non-users. Propensity score methodologies were used in order to minimize selection bias and strengthen causal inferences. The enrolled obstructive sleep apnea subjects (n = 822) were newly diagnosed with moderate to severe obstructive sleep apnea who were starting positive airway pressure treatment, and the general population subjects (n = 742) were randomly selected Icelanders. The Short Form 12 was used to measure quality of life. Untreated patients with obstructive sleep apnea had a worse quality of life when compared with the general population. This effect remained significant after using propensity scores to select samples, balanced with regard to age, body mass index, gender, smoking, diabetes, hypertension and cardiovascular disease. We did not find significant overall differences between full and non-users of positive airway pressure in improvement of quality of life from baseline to follow-up. However, there was a trend towards more improvement in physical quality of life for positive airway pressure-adherent patients, and the most obese subjects improved their physical quality of life more. The results suggest that co-morbidities of obstructive sleep apnea, such as obesity, insomnia and daytime sleepiness, have a great effect on life qualities and need to be taken into account and addressed with additional interventions. © 2014 European Sleep Research Society.

  3. Selected Effects of a Curriculum Integration Intervention on the Mathematics Performance of Secondary Students Enrolled in an Agricultural Power and Technology Course: An Experimental Study

    ERIC Educational Resources Information Center

    Parr, Brian; Edwards, M. Craig; Leising, James G.

    2009-01-01

    The purpose of this study was to empirically test the posit that students who participated in a contextualized, mathematics-enhanced high school agricultural power and technology (APT) curriculum and aligned instructional approach would develop a deeper and more sustained understanding of selected mathematics concepts than those students who…

  4. Positive selection and functional divergence of farnesyl pyrophosphate synthase genes in plants.

    PubMed

    Qian, Jieying; Liu, Yong; Chao, Naixia; Ma, Chengtong; Chen, Qicong; Sun, Jian; Wu, Yaosheng

    2017-02-04

    Farnesyl pyrophosphate synthase (FPS) belongs to the short-chain prenyltransferase family, and it performs a conserved and essential role in the terpenoid biosynthesis pathway. However, its classification, evolutionary history, and the forces driving the evolution of FPS genes in plants remain poorly understood. Phylogeny and positive selection analysis was used to identify the evolutionary forces that led to the functional divergence of FPS in plants, and recombinant detection was undertaken using the Genetic Algorithm for Recombination Detection (GARD) method. The dataset included 68 FPS variation pattern sequences (2 gymnosperms, 10 monocotyledons, 54 dicotyledons, and 2 outgroups). This study revealed that the FPS gene was under positive selection in plants. No recombinant within the FPS gene was found. Therefore, it was inferred that the positive selection of FPS had not been influenced by a recombinant episode. The positively selected sites were mainly located in the catalytic center and functional areas, which indicated that the 98S and 234D were important positively selected sites for plant FPS in the terpenoid biosynthesis pathway. They were located in the FPS conserved domain of the catalytic site. We inferred that the diversification of FPS genes was associated with functional divergence and could be driven by positive selection. It was clear that protein sequence evolution via positive selection was able to drive adaptive diversification in plant FPS proteins. This study provides information on the classification and positive selection of plant FPS genes, and the results could be useful for further research on the regulation of triterpenoid biosynthesis.

  5. Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

    PubMed

    Morozova, Margarita A; Lepilkina, Taisiya A; Rupchev, Georgy E; Beniashvily, Allan G; Burminskiy, Denis S; Potanin, Sergey S; Bondarenko, Evgeny V; Kazey, Vasily I; Lavrovsky, Yan; Ivachtchenko, Alexandre V

    2014-08-01

    The serotoninergic system as a target for add-on treatment seems to be a promising approach in patients with schizophrenia. To clarify if selective 5HT-6 antagonist AVN-211 (CD-008-0173) adds clinical and cognitive effects to stable antipsychotic treatment. A randomized, double-blind, placebo-controlled, add-on, 4r-week trial in 47 schizophrenia patients (21 patients receiving study drug and 26 receiving placebo) who were stabilized on antipsychotic medication was performed. Seventeen patients from the study drug group and 25 patients from the placebo group completed the trial. Treatment effects were measured using clinical rating scales and attention tests. With no differences at baseline, there was a significant difference between the groups in Positive and Negative Syndrome Scale (PANSS) positive subscale score (p = 0.058) in favor of patients in the treatment group at the endpoint. The PANSS positive subscore (p = 0.0068) and Clinical Global Impression-Severity (CGI-S) (p = 0.048) score significantly changed only in the treatment group. Only in the placebo group were significant changes in Calgary Depression Rating Scale (CDRS) total score registered. The indices of attention tests at endpoint did not show differences between the groups, with the exception of the scope of change in the results of the subtest VIII of the Wechsler Adult Intelligence Scale (WAIS), which showed difference between the groups (p = 0.02) and was significantly larger in the treatment group. Only inside the study drug group, significant changes in selectivity and continuous attention were observed regarding total correct responses (p = 0.0038) and reaction time (p = 0.058) in the Continuous Attention Task (CAT) test. Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.

  6. Above- and below-ground effects of plant diversity depend on species origin: an experimental test with multiple invaders.

    PubMed

    Kuebbing, Sara E; Classen, Aimée T; Sanders, Nathan J; Simberloff, Daniel

    2015-11-01

    Although many plant communities are invaded by multiple nonnative species, we have limited information on how a species' origin affects ecosystem function. We tested how differences in species richness and origin affect productivity and seedling establishment. We created phylogenetically paired native and nonnative plant communities in a glasshouse experiment to test diversity-productivity relationships and responsible mechanisms (i.e. selection or complementarity effects). Additionally, we tested how productivity and associated mechanisms influenced seedling establishment. We used diversity-interaction models to describe how species' interactions influenced diversity-productivity relationships. Communities with more species had higher total biomass than did monoculture communities, but native and nonnative communities diverged in root : shoot ratios and the mechanism responsible for increased productivity: positive selection effect in nonnative communities and positive complementarity effect in native communities. Seedling establishment was 46% lower in nonnative than in native communities and was correlated with the average selection effect. Interspecific interactions contributed to productivity patterns, but the specific types of interactions differed between native and nonnative communities. These results reinforce findings that the diversity-productivity mechanisms in native and nonnative communities differ and are the first to show that these mechanisms can influence seedling establishment and that different types of interactions influence diversity-productivity relationships. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  7. The GTPase Rac-1 controls cell fate in the thymus by diverting thymocytes from positive to negative selection.

    PubMed

    Gomez, M; Kioussis, D; Cantrell, D A

    2001-11-01

    The positive selection of CD4 or CD8 single-positive mature peripheral T lymphocytes and the deletion of self-reactive cells are crucial for central tolerance in the peripheral immune system. Previously, the guanine nucleotide binding protein Rac-1 has been shown to control pre-T cell development. The present report now describes the actions of Rac-1 in thymocyte selection. The study reveals that this molecule has the striking and unique ability to efficiently divert cells from positive selection into a pathway of negative selection and deletion. The ability of Rac-1 to switch thymocytes from a destiny of positive to negative selection identifies this molecule as a critical regulator of the developmental processes in T cells that are essential for immune homeostasis.

  8. 'Ecstasy' as a social drug: MDMA preferentially affects responses to emotional stimuli with social content.

    PubMed

    Wardle, Margaret C; Kirkpatrick, Matthew G; de Wit, Harriet

    2014-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is used recreationally to improve mood and sociability, and has generated clinical interest as a possible adjunct to psychotherapy. One way that MDMA may produce positive 'prosocial' effects is by changing responses to emotional stimuli, especially stimuli with social content. Here, we examined for the first time how MDMA affects subjective responses to positive, negative and neutral emotional pictures with and without social content. We hypothesized that MDMA would dose-dependently increase reactivity to positive emotional stimuli and dampen reactivity to negative stimuli, and that these effects would be most pronounced for pictures with people in them. The data were obtained from two studies using similar designs with healthy occasional MDMA users (total N = 101). During each session, participants received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and negative responses to standardized positive, negative and neutral pictures with and without social content. MDMA increased positive ratings of positive social pictures, but reduced positive ratings of non-social positive pictures. We speculate this 'socially selective' effect contributes to the prosocial effects of MDMA by increasing the comparative value of social contact and closeness with others. This effect may also contribute to its attractiveness to recreational users. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Patient positioning and ventilator-associated pneumonia.

    PubMed

    Hess, Dean R

    2005-07-01

    Rotational beds, prone position, and semi-recumbent position have been proposed as procedures to prevent ventilator-associated pneumonia (VAP). Rotational therapy uses a special bed designed to turn continuously, or nearly continuously, the patient from side to side; specific designs include kinetic therapy and continuous lateral rotation therapy. A meta-analysis of studies evaluating the effect of rotational bed therapy shows a decrease in the risk of pneumonia but no effect on mortality. Two studies reported a lower risk of VAP in patients placed in a prone position, with no effect on mortality. Studies using radiolabeled enteral feeding solutions in mechanically ventilated patients have reported that aspiration of gastric contents occurs to a greater degree when patients are in the supine position, compared with the semirecumbent position. One study reported a lower rate of VAP in patients randomized to semi-recumbent compared to supine position. Although each of the techniques discussed in this paper has been shown to reduce the risk of VAP, none has been shown to affect mortality. The available evidence suggests that semi-recumbent position should be used routinely, rotational therapy should be considered in selected patients, and prone position should not be used as a technique to reduce the risk of VAP.

  10. Hemizygosity Enhances Purifying Selection: Lack of Fast-Z Evolution in Two Satyrine Butterflies.

    PubMed

    Rousselle, Marjolaine; Faivre, Nicolas; Ballenghien, Marion; Galtier, Nicolas; Nabholz, Benoit

    2016-10-23

    The fixation probability of a recessive beneficial mutation is increased on the X or Z chromosome, relative to autosomes, because recessive alleles carried by X or Z are exposed to selection in the heterogametic sex. This leads to an increased dN/dS ratio on sex chromosomes relative to autosomes, a pattern called the "fast-X" or "fast-Z" effect. Besides positive selection, the strength of genetic drift and the efficacy of purifying selection, which affect the rate of molecular evolution, might differ between sex chromosomes and autosomes. Disentangling the complex effects of these distinct forces requires the genome-wide analysis of polymorphism, divergence and gene expression data in a variety of taxa. Here we study the influence of hemizygosity of the Z chromosome in Maniola jurtina and Pyronia tithonus, two species of butterflies (Lepidoptera, Nymphalidae, Satyrinae). Using transcriptome data, we compare the strength of positive and negative selection between Z and autosomes accounting for sex-specific gene expression. We show that M. jurtina and P. tithonus do not experience a faster, but rather a slightly slower evolutionary rate on the Z than on autosomes. Our analysis failed to detect a significant difference in adaptive evolutionary rate between Z and autosomes, but comparison of male-biased, unbiased and female-biased Z-linked genes revealed an increased efficacy of purifying selection against recessive deleterious mutations in female-biased Z-linked genes. This probably contributes to the lack of fast-Z evolution of satyrines. We suggest that the effect of hemizygosity on the fate of recessive deleterious mutations should be taken into account when interpreting patterns of molecular evolution in sex chromosomes vs. autosomes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. 36 CFR 72.50 - Grant selection criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... proposal may lead to a positive, systemic change in how park and recreation services are provided. Extent... method approaches which may prove to be more effective under the private sector. This should in no way...

  12. Using positive youth development constructs to design a money management curriculum for junior secondary school students in Hong Kong.

    PubMed

    Lau, Patrick S Y; Lam, C M; Law, Ben M F; Poon, Y H

    2011-01-01

    This paper aims to discuss the relationships between the selected positive youth development constructs and the enhancement of Hong Kong junior secondary school students' money management skills, values, and attitudes. Various issues of money management of adolescents are reviewed. These issues include the need for money management programs for adolescents, the content and coverage of an appropriate money management program, and its relationships with the selected positive youth development constructs. The curriculum units for secondary 3 students are taken as examples to illustrate the design of the program. It is believed that promoting cognitive competence, self-efficacy, and spirituality could be an effective way to enhance students' money management skills, values, and attitudes, thus preparing them better for facing the finance-related issues in life.

  13. Using Positive Youth Development Constructs to Design a Money Management Curriculum for Junior Secondary School Students in Hong Kong

    PubMed Central

    Lau, Patrick S. Y.; Lam, C. M.; Law, Ben M. F.; Poon, Y. H.

    2011-01-01

    This paper aims to discuss the relationships between the selected positive youth development constructs and the enhancement of Hong Kong junior secondary school students' money management skills, values, and attitudes. Various issues of money management of adolescents are reviewed. These issues include the need for money management programs for adolescents, the content and coverage of an appropriate money management program, and its relationships with the selected positive youth development constructs. The curriculum units for secondary 3 students are taken as examples to illustrate the design of the program. It is believed that promoting cognitive competence, self-efficacy, and spirituality could be an effective way to enhance students' money management skills, values, and attitudes, thus preparing them better for facing the finance-related issues in life. PMID:22125469

  14. Charges drive selection of specific antibodies by phage display.

    PubMed

    Persson, Helena; Persson, Jonas; Danielsson, Lena; Ohlin, Mats

    2010-02-28

    Phage display technology has emerged as a leading approach to select proteins with improved properties for many different types of applications. The selection typically selects not only for improved binding properties but also for other factors such as efficiency of protein production and folding in Escherichia coli, the host in which the proteins and the phage are produced. Furthermore, the selection methodology is likely to influence the character of retrieved variants. We have now defined the extent whereby the charge of the displayed proteins influence the selection process, resulting in an increased average positive charge among selected proteins in comparison to the proteins that are harbored in the library before selection. Implications of and possible routes to minimize this effect are discussed. 2009 Elsevier B.V. All rights reserved.

  15. 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.

  16. Structure-Based Design and Synthesis of Harmine Derivatives with Different Selectivity Profiles in Kinase versus Monoamine Oxidase Inhibition.

    PubMed

    Bálint, Balázs; Wéber, Csaba; Cruzalegui, Francisco; Burbridge, Mike; Kotschy, Andras

    2017-06-21

    Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is an emerging biological target with implications in diverse therapeutic areas such as neurological disorders (Down syndrome, in particular), metabolism, and oncology. Harmine, a natural product that selectively inhibits DYRK1A amongst kinases, could serve as a tool compound to better understand the biological processes that arise from DYRK1A inhibition. On the other hand, harmine is also a potent inhibitor of monoamine oxidase A (MAO-A). Using structure-based design, we synthesized a collection of harmine analogues with tunable selectivity toward these two enzymes. Modifications at the 7-position typically decreased affinity for DYRK1A, whereas substitution at the 9-position had a similar effect on MAO-A inhibition but DYRK1A inhibition was maintained. The resulting collection of compounds can help to understand the biological role of DYRK1A and also to assess the interference in the biological effect originating in MAO-A inhibition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides.

    PubMed

    Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2017-01-01

    Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2-4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ F ST ≤ 0.15) or high genetic differentiation ( F ST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different F ST -outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement.

  18. Effects of "Like Type" Sex Pairings between Applicants-Principals and Type of Focal Position Considered at the Screening Stage of the Selection Process

    ERIC Educational Resources Information Center

    Young, I. Phillip

    2005-01-01

    This study addresses the screening decisions for a national random sample of high school principals as viewed from the attraction-similarity theory of interpersonal perceptions. Independent variables are the sex of principals, sex of applicants, and the type of focal positions sought by hypothetical job applicants (teacher or counselor). Dependent…

  19. Positivity effect in source attributions of arousal-matched emotional and non-emotional words during item-based directed forgetting.

    PubMed

    Gallant, Sara N; Yang, Lixia

    2014-01-01

    Consistent with their emphasis on emotional goals, older adults often exhibit a positivity bias in attention and memory relative to their young counterparts (i.e., a positivity effect). The current study sought to determine how this age-related positivity effect would impact intentional forgetting of emotional words, a process critical to efficient operation of memory. Using an item-based directed forgetting task, 36 young and 36 older adults studied a series of arousal-equivalent words that varied in valence (i.e., positive, negative, and neutral). Each word was followed by a cue to either remember or forget the word. A subsequent "tagging" recognition task required classification of items as to-be-remembered (TBR), to-be-forgotten (TBF), or new as a measure of directed forgetting and source attribution in participants' memory. Neither young nor older adults' intentional forgetting was affected by the valence of words. A goal-consistent valence effect did, however, emerge in older adults' source attribution performance. Specifically, older adults assigned more TBR-cues to positive words and more TBF-cues to negative words. Results are discussed in light of existing literature on emotion and directed forgetting as well as the socioemotional selectivity theory underlying the age-related positivity effect.

  20. Positivity effect in source attributions of arousal-matched emotional and non-emotional words during item-based directed forgetting

    PubMed Central

    Gallant, Sara N.; Yang, Lixia

    2014-01-01

    Consistent with their emphasis on emotional goals, older adults often exhibit a positivity bias in attention and memory relative to their young counterparts (i.e., a positivity effect). The current study sought to determine how this age-related positivity effect would impact intentional forgetting of emotional words, a process critical to efficient operation of memory. Using an item-based directed forgetting task, 36 young and 36 older adults studied a series of arousal-equivalent words that varied in valence (i.e., positive, negative, and neutral). Each word was followed by a cue to either remember or forget the word. A subsequent “tagging” recognition task required classification of items as to-be-remembered (TBR), to-be-forgotten (TBF), or new as a measure of directed forgetting and source attribution in participants' memory. Neither young nor older adults' intentional forgetting was affected by the valence of words. A goal-consistent valence effect did, however, emerge in older adults' source attribution performance. Specifically, older adults assigned more TBR-cues to positive words and more TBF-cues to negative words. Results are discussed in light of existing literature on emotion and directed forgetting as well as the socioemotional selectivity theory underlying the age-related positivity effect. PMID:25477850

  1. Enhancing the Performance of LibSVM Classifier by Kernel F-Score Feature Selection

    NASA Astrophysics Data System (ADS)

    Sarojini, Balakrishnan; Ramaraj, Narayanasamy; Nickolas, Savarimuthu

    Medical Data mining is the search for relationships and patterns within the medical datasets that could provide useful knowledge for effective clinical decisions. The inclusion of irrelevant, redundant and noisy features in the process model results in poor predictive accuracy. Much research work in data mining has gone into improving the predictive accuracy of the classifiers by applying the techniques of feature selection. Feature selection in medical data mining is appreciable as the diagnosis of the disease could be done in this patient-care activity with minimum number of significant features. The objective of this work is to show that selecting the more significant features would improve the performance of the classifier. We empirically evaluate the classification effectiveness of LibSVM classifier on the reduced feature subset of diabetes dataset. The evaluations suggest that the feature subset selected improves the predictive accuracy of the classifier and reduce false negatives and false positives.

  2. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors.

    PubMed

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-02-01

    Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. E1R was tested for sigma receptor binding activity in a [³H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca²⁺ concentration ([Ca²⁺](i)) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca²⁺](i) increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. © 2013 The British Pharmacological Society.

  3. Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats.

    PubMed

    Mohler, Eric G; Franklin, Stanley R; Rueter, Lynne E

    2014-01-01

    Neuronal α4β2* nicotinic acetylcholine receptors mediate cognition, pain, and the discriminative and reinforcing effects of nicotine. In addition to traditional orthosteric agonists, α4β2* positive allosteric modulators (PAMs) have recently been identified. With increased subtype selectivity relative to agonists, PAMs administered alone or in combination with low-dose α4β2* agonists may be used as powerful tools for increasing our understanding of α4β2* pharmacology. The present experiments tested the nicotine discriminative-stimulus effects of the α4β2* PAM NS9283 (A-969933) in the presence and absence of low-dose nicotine or nicotinic subtype-selective agonist. Rats were trained to discriminate 0.4 mg/kg nicotine from saline in a two-lever drug discrimination paradigm. In subsequent generalization tests, rats were administered nicotine, the α4β2*-preferring agonist ABT-594, and NS9283, alone or in two-drug combinations. Nicotine and ABT-594 showed dose-dependent nicotine generalization. NS9283 alone resulted in a non-significant increase in nicotine-appropriate lever selection. Combination of non-effective doses of nicotine or ABT-594 with escalating doses of NS9283 resulted in a complete conversion to 100 % nicotine-appropriate choice in the case of nicotine combination and incomplete, though significant, generalization for ABT-594. The α4β2* PAM NS9283 alone did not produce nicotine-like discriminative effects, but did demonstrate dose-related increases in nicotine lever choice when combined with a non-effective dose of nicotine or the α4β2* agonist ABT-594. This finding provides confirmation of the positive allosteric modulating effect of NS9283 in a functional in vivo paradigm. NS9283 is a potentially valuable tool for studying the role of α4β2* receptors in various nicotinic acetylcholine receptor-related functions.

  4. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    PubMed Central

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  5. Fitts's law in a selective reaching task: the proximity-to-hand effect of action-centered attention revisited.

    PubMed

    Welsh, Timothy N; Zbinden, Michele

    2009-01-01

    The "proximity-to-hand" effect refers to the finding that distractors between the home position and the target cause more interference in a selective reaching movement than distractors farther from the home position. Based largely on the proximity-to-hand effect, Tipper, Lortie, and Baylis (1992) proposed that attention is distributed in an action-centered framework such that the interference caused by a specific stimulus depends on the action. The current experiments sought to determine if there is an attentional preference for stimuli closer to home or for stimuli that activate more efficiently executed actions regardless of the location. Results supported the latter hypothesis in that the greatest interference was observed when the distractor activated an action with a lower index of difficulty than the target, even though that distractor was farther from home than the target. These findings indicate that the action context mediates the influence that nontarget stimuli have on the processing of target responses.

  6. Human papillomavirus detection and typing using a nested-PCR-RFLP assay.

    PubMed

    Coser, Janaina; Boeira, Thaís da Rocha; Fonseca, André Salvador Kazantzi; Ikuta, Nilo; Lunge, Vagner Ricardo

    2011-01-01

    It is clinically important to detect and type human papillomavirus (HPV) in a sensitive and specific manner. Development of a nested-polymerase chain reaction-restriction fragment length polymorphism (nested-PCR-RFLP) assay to detect and type HPV based on the analysis of L1 gene. Analysis of published DNA sequence of mucosal HPV types to select sequences of new primers. Design of an original nested-PCR assay using the new primers pair selected and classical MY09/11 primers. HPV detection and typing in cervical samples using the nested-PCR-RFLP assay. The nested-PCR-RFLP assay detected and typed HPV in cervical samples. Of the total of 128 clinical samples submitted to simple PCR and nested-PCR for detection of HPV, 37 (28.9%) were positive for the virus by both methods and 25 samples were positive only by nested-PCR (67.5% increase in detection rate compared with single PCR). All HPV positive samples were effectively typed by RFLP assay. The method of nested-PCR proved to be an effective diagnostic tool for HPV detection and typing.

  7. Effects of aging on neural connectivity underlying selective memory for emotional scenes

    PubMed Central

    Waring, Jill D.; Addis, Donna Rose; Kensinger, Elizabeth A.

    2012-01-01

    Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults’ encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults’ connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item. PMID:22542836

  8. Effects of aging on neural connectivity underlying selective memory for emotional scenes.

    PubMed

    Waring, Jill D; Addis, Donna Rose; Kensinger, Elizabeth A

    2013-02-01

    Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults' encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults' connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item. Published by Elsevier Inc.

  9. Computational Prediction of Protein Epsilon Lysine Acetylation Sites Based on a Feature Selection Method.

    PubMed

    Gao, JianZhao; Tao, Xue-Wen; Zhao, Jia; Feng, Yuan-Ming; Cai, Yu-Dong; Zhang, Ning

    2017-01-01

    Lysine acetylation, as one type of post-translational modifications (PTM), plays key roles in cellular regulations and can be involved in a variety of human diseases. However, it is often high-cost and time-consuming to use traditional experimental approaches to identify the lysine acetylation sites. Therefore, effective computational methods should be developed to predict the acetylation sites. In this study, we developed a position-specific method for epsilon lysine acetylation site prediction. Sequences of acetylated proteins were retrieved from the UniProt database. Various kinds of features such as position specific scoring matrix (PSSM), amino acid factors (AAF), and disorders were incorporated. A feature selection method based on mRMR (Maximum Relevance Minimum Redundancy) and IFS (Incremental Feature Selection) was employed. Finally, 319 optimal features were selected from total 541 features. Using the 319 optimal features to encode peptides, a predictor was constructed based on dagging. As a result, an accuracy of 69.56% with MCC of 0.2792 was achieved. We analyzed the optimal features, which suggested some important factors determining the lysine acetylation sites. We developed a position-specific method for epsilon lysine acetylation site prediction. A set of optimal features was selected. Analysis of the optimal features provided insights into the mechanism of lysine acetylation sites, providing guidance of experimental validation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. mGlu₅-GABAB interplay in animal models of positive, negative and cognitive symptoms of schizophrenia.

    PubMed

    Wierońska, Joanna M; Kłeczek, Natalia; Woźniak, Monika; Gruca, Piotr; Łasoń-Tyburkiewicz, Magdalena; Papp, Mariusz; Brański, Piotr; Burnat, Grzegorz; Pilc, Andrzej

    2015-09-01

    Diverse preclinical studies exploiting the modulation of the GABAergic and/or glutamatergic system in brain via metabotropic receptors suggest their potential therapeutic utility. GS39783 and CDPPB, positive allosteric modulators of GABAB and mGlu5 receptors, were previously shown to reverse behavioral phenotypes in animal models to mimic selected (predominantly positive) symptoms of schizophrenia. In the present study we investigated the activity of selected GABAB (GS39783 and CGP7930) and mGlu5 (CDPPB) positive allosteric modulators. We focused mainly on the aspects of their efficacy in the models of negative and cognitive symptoms of schizophrenia. We used modified swim test, social interactions (models of negative symptoms) and novel object recognition (model of cognitive disturbances). The activity of the compounds was also tested in haloperidol-induced catalepsy test. The mutual interaction between GABAB/mGlu5 ligands was investigated as well. In the second part of the study, DHPG-induced PI hydrolysis in the presence of GABAB receptor antagonist (SKF97541), and SKF97541-induced inhibition of cAMP formation in the presence of DHPG, was performed. Both mGlu5 and GABAB receptor modulators effectively reversed MK-801-induced deficits in behavioral models of schizophrenia. Moreover, the concomitant administration of sub-effective doses of CDPPB and GS39783 induced a clear antipsychotic-like effect in all the procedures used, except DOI-induced head twitches. The concomitant administration of group I mGlu and GABAB agonists did not displayed any synergistic effects in vitro. Summing up, an activation of both types of receptor may be a promising mechanism for the development of novel antipsychotic drugs, efficacious toward positive, negative and cognitive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Speeding Up Microevolution: The Effects of Increasing Temperature on Selection and Genetic Variance in a Wild Bird Population

    PubMed Central

    Husby, Arild; Visser, Marcel E.; Kruuk, Loeske E. B.

    2011-01-01

    The amount of genetic variance underlying a phenotypic trait and the strength of selection acting on that trait are two key parameters that determine any evolutionary response to selection. Despite substantial evidence that, in natural populations, both parameters may vary across environmental conditions, very little is known about the extent to which they may covary in response to environmental heterogeneity. Here we show that, in a wild population of great tits (Parus major), the strength of the directional selection gradients on timing of breeding increased with increasing spring temperatures, and that genotype-by-environment interactions also predicted an increase in additive genetic variance, and heritability, of timing of breeding with increasing spring temperature. Consequently, we therefore tested for an association between the annual selection gradients and levels of additive genetic variance expressed each year; this association was positive, but non-significant. However, there was a significant positive association between the annual selection differentials and the corresponding heritability. Such associations could potentially speed up the rate of micro-evolution and offer a largely ignored mechanism by which natural populations may adapt to environmental changes. PMID:21408101

  12. Time perspective and positivity effects in Alzheimer's disease.

    PubMed

    Bohn, Linzy; Kwong See, Sheree T; Fung, Helene H

    2016-09-01

    This study tested whether time perspective, a central tenant of socioemotional selectivity theory (Carstensen, 2006), moderates positivity effects in emotional memory. To provide measures of time perspective, young (YA; M = 22.48 years), young-old (YO; M = 67.56 years), old-old adults (OO; M = 80.24 years), and participants with moderate severity Alzheimer's disease (PAD; M = 84.28 years) completed a line task and reported subjective age. As expected, YA, YO, and OO reported successively more constrained future time perspectives. PAD showed distortion in time perspective, envisioning a future comparable with the YO, although closer matched in chronological age to OO adults. To evince positivity effects, participants were oriented to pairs of emotional images and were then tested for memory (recall and recognition) of the images. Recall and recognition memory for the images indicated an age-related advantage for positive over negative material (positivity effects). Time perspective, however, did not moderate these age effects. In memory performance, PAD were more comparable with OO adults with whom they shared a similar chronological age, rather than YO adults, who had a corresponding time perspective. These results suggest that age correlates that are shared by PAD and OO, such as reduced processing resources, rather than time perspective, may drive the age associated positivity effects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Characterizing the effects of amplitude, frequency and limb position on vibration induced movement illusions: Implications in sensory-motor rehabilitation.

    PubMed

    Schofield, Jonathon S; Dawson, Michael R; Carey, Jason P; Hebert, Jacqueline S

    2015-01-01

    Strategic vibration of musculotendinous regions of a limb elicits illusionary sensations of movement. As a rehabilitation technique, this 'kinesthetic illusion' has demonstrated beneficial results for numerous sensory-motor disorders. However, literature shows little consistency in the vibration parameters or body positioning used, and their effects have yet to be comprehensively investigated. To characterize the effects of the vibration amplitude, frequency, and limb position on the kinesthetic illusion. Movement illusions were induced in 12 participants' biceps and triceps. The effect of amplitude (0.1 to 0.5 mm), frequency (70 to 110 Hz), and two limb positions were quantified on the strength of illusion (SOI), range of motion (ROM) and velocity. Amplitude significantly affected the illusionary SOI, ROM and velocity in the biceps and triceps (p< 0.05). Increasing amplitude resulted in an increase of all three output variables. Limb position showed an effect on illusionary velocity in the biceps as well as ROM and velocity in the triceps (p< 0.05). Frequency demonstrated no statistical effect. Amplitude demonstrated the most profound impact on the kinesthetic illusion in the experimental ranges tested. This work may help guide clinicians and researchers in selecting appropriate vibratory parameters and body positions to consistently elicit and manipulate the kinesthetic illusion.

  14. 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

  15. Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase.

    PubMed

    Romero, F Anthony; Du, Wu; Hwang, Inkyu; Rayl, Thomas J; Kimball, F Scott; Leung, Donmienne; Hoover, Heather S; Apodaca, Richard L; Breitenbucher, J Guy; Cravatt, Benjamin F; Boger, Dale L

    2007-03-08

    A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurrent with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, nonaromatic C5-substituents was also explored and revealed that the K(i) follows a well-defined correlation with the Hammett sigma(p) constant (rho = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency, leading to inhibitors with K(i)s as low as 400 pM (20n). Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases, reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH.

  16. Method and apparatus for powering an electrodeless lamp with reduced radio frequency interference

    DOEpatents

    Simpson, James E.

    1999-01-01

    An electrodeless lamp waveguide structure includes tuned absorbers for spurious RF signals. A lamp waveguide with an integral frequency selective attenuation includes resonant absorbers positioned within the waveguide to absorb spurious out-of-band RF energy. The absorbers have a negligible effect on energy at the selected frequency used to excite plasma in the lamp. In a first embodiment, one or more thin slabs of lossy magnetic material are affixed to the sidewalls of the waveguide at approximately one quarter wavelength of the spurious signal from an end wall of the waveguide. The positioning of the lossy material optimizes absorption of power from the spurious signal. In a second embodiment, one or more thin slabs of lossy magnetic material are used in conjunction with band rejection waveguide filter elements. In a third embodiment, one or more microstrip filter elements are tuned to the frequency of the spurious signal and positioned within the waveguide to couple and absorb the spurious signal's energy. All three embodiments absorb negligible energy at the selected frequency and so do not significantly diminish the energy efficiency of the lamp.

  17. Method and apparatus for powering an electrodeless lamp with reduced radio frequency interference

    DOEpatents

    Simpson, J.E.

    1999-06-08

    An electrodeless lamp waveguide structure includes tuned absorbers for spurious RF signals. A lamp waveguide with an integral frequency selective attenuation includes resonant absorbers positioned within the waveguide to absorb spurious out-of-band RF energy. The absorbers have a negligible effect on energy at the selected frequency used to excite plasma in the lamp. In a first embodiment, one or more thin slabs of lossy magnetic material are affixed to the sidewalls of the waveguide at approximately one quarter wavelength of the spurious signal from an end wall of the waveguide. The positioning of the lossy material optimizes absorption of power from the spurious signal. In a second embodiment, one or more thin slabs of lossy magnetic material are used in conjunction with band rejection waveguide filter elements. In a third embodiment, one or more microstrip filter elements are tuned to the frequency of the spurious signal and positioned within the waveguide to couple and absorb the spurious signal's energy. All three embodiments absorb negligible energy at the selected frequency and so do not significantly diminish the energy efficiency of the lamp. 18 figs.

  18. Adaptive Evolution as a Predictor of Species-Specific Innate Immune Response.

    PubMed

    Webb, Andrew E; Gerek, Z Nevin; Morgan, Claire C; Walsh, Thomas A; Loscher, Christine E; Edwards, Scott V; O'Connell, Mary J

    2015-07-01

    It has been proposed that positive selection may be associated with protein functional change. For example, human and macaque have different outcomes to HIV infection and it has been shown that residues under positive selection in the macaque TRIM5α receptor locate to the region known to influence species-specific response to HIV. In general, however, the relationship between sequence and function has proven difficult to fully elucidate, and it is the role of large-scale studies to help bridge this gap in our understanding by revealing major patterns in the data that correlate genotype with function or phenotype. In this study, we investigate the level of species-specific positive selection in innate immune genes from human and mouse. In total, we analyzed 456 innate immune genes using codon-based models of evolution, comparing human, mouse, and 19 other vertebrate species to identify putative species-specific positive selection. Then we used population genomic data from the recently completed Neanderthal genome project, the 1000 human genomes project, and the 17 laboratory mouse genomes project to determine whether the residues that were putatively positively selected are fixed or variable in these populations. We find evidence of species-specific positive selection on both the human and the mouse branches and we show that the classes of genes under positive selection cluster by function and by interaction. Data from this study provide us with targets to test the relationship between positive selection and protein function and ultimately to test the relationship between positive selection and discordant phenotypes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Genetic selection increases parthenogenesis in Chinese painted quail (Coturnix chinensis).

    PubMed

    Parker, H M; Kiess, A S; Wells, J B; Young, K M; Rowe, D; McDaniel, C D

    2010-07-01

    Parthenogenesis, embryonic development of an unfertilized egg, occurs naturally in turkey, chicken, and quail species. In fact, parthenogenesis in turkeys and chickens can be increased by genetic selection. However, it is unknown if genetic selection for parthenogenesis is effective in quail or if selection for parthenogenesis affects egg production. Therefore, the objectives of this study were to determine if the incidence of parthenogenesis in quail could be increased by genetic selection and if selection for this trait affects egg production. To prevent fertilization, 1,090 females were caged separately from males at 4 wk of age and then caged individually at 6 wk of age to monitor egg production. Eggs were collected daily, labeled, and stored for 0 to 3 d. After 10 d of incubation, 20 unfertilized eggs from each hen were examined for the occurrence of parthenogenesis and embryonic growth. In the parent (P) generation and subsequent generations (1 to 4), hens laying eggs containing parthenogenetic development and males whose sisters or mothers exhibited parthenogenesis were used for breeding. There was a linear increase in the percentage of hens exhibiting parthenogenesis as generation of selection increased. With each successive generation, there was a quadratic response in the percentage of eggs positive for parthenogenesis. When compared with the P generation, parthenogenesis was almost 3 times greater for eggs laid by the fourth generation (4.6 to 12.5%, respectively). Even when only hens exhibiting parthenogenesis were examined, the percentage of eggs demonstrating embryonic development responded quadratically with generation of selection. The embryonic size at 10 d of incubation was greater for each subsequent generation when compared with the P generation. There was a linear decrease in both egg production and the average position of an egg in a clutch as generation of selection increased. In conclusion, genetic selection for parthenogenesis increased the incidence of parthenogenesis and embryonic size but decreased egg production and average position of an egg in a clutch as generations of selection increased.

  20. The role of Parenting and Goal Selection in Positive Youth Development: A Person-Centered Approach

    ERIC Educational Resources Information Center

    Napolitano, Christopher M.; Bowers, Edmond P.; Gestsdottir, Steinunn; Depping, Miriam; von Eye, Alexander; Chase, Paul; Lerner, Jacqueline V.

    2011-01-01

    Using a person-centered approach, we examined the relations between goal selection, various indicators of parenting, and positive development among 510 Grades 9 to 11 participants (68% female) in the 4-H Study of Positive Youth Development (PYD), a longitudinal study involving U.S. adolescents. Goal selection was operationalized by the "Selection"…

  1. Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates

    PubMed Central

    Carlson, Joshua M.; Rubin, Denis; Cha, Jiook; Mujica-Parodi, Lilianne

    2015-01-01

    The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, ‘uncertain’ (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of ‘uncertain’ clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive. PMID:24984958

  2. The Pleasantness of Visual Symmetry: Always, Never or Sometimes

    PubMed Central

    Pecchinenda, Anna; Bertamini, Marco; Makin, Alexis David James; Ruta, Nicole

    2014-01-01

    There is evidence of a preference for visual symmetry. This is true from mate selection in the animal world to the aesthetic appreciation of works of art. It has been proposed that this preference is due to processing fluency, which engenders positive affect. But is visual symmetry pleasant? Evidence is mixed as explicit preferences show that this is the case. In contrast, implicit measures show that visual symmetry does not spontaneously engender positive affect but it depends on participants intentionally assessing visual regularities. In four experiments using variants of the affective priming paradigm, we investigated when visual symmetry engenders positive affect. Findings showed that, when no Stroop-like effects or post-lexical mechanisms enter into play, visual symmetry spontaneously elicits positive affect and results in affective congruence effects. PMID:24658112

  3. Oncolytic Adenoviruses Targeted to Human Papilloma Virus-Positive Head and Neck Squamous Cell Carcinomas

    PubMed Central

    LaRocca, Christopher J.; Han, Joohee; Oliveira, Amanda R.; Davydova, Julia; Herzberg, Mark; Gopalakrishnan, Rajaram; Yamamoto, Masato

    2016-01-01

    Objectives In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins. Methods Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells. In vitro assays were performed to analyze the transduction efficiency of the vectors and the cell viability following viral infection. Then, the UPCI SCC 090 cell line (HPV-positive) was used to establish subcutaneous tumors in the flanks of nude mice. The tumors were then treated with either one dose of the virus or four doses (injected every fourth day). Results The transduction analysis with luciferase-expressing viruses demonstrated that the 5/3 fiber modification maximized virus infectivity. In vitro, both viruses (5/3Δ24 and 5/3CB016) demonstrated profound oncolytic effects. The 5/3CB016 virus was selective for only HPV-positive HNSCC cells, whereas the 5/3Δ24 virus killed HNSCC cells regardless of HPV status. In vivo, single injections of both viruses demonstrated anti-tumor effects until only 6–8 days following viral inoculation. However, after four viral injections, there was statistically significant reduction in tumor growth when compared to the control group (p<0.05). Conclusion CRAds targeted to HPV-positive HNSCCs demonstrated excellent in vitro and in vivo therapeutic effects, and they have the potential to be clinically translated as a novel treatment modality for this emerging disease. PMID:27086483

  4. Selection of chemotherapy for glioblastoma expressing O6-methylguanine-DNA methyltransferase

    PubMed Central

    IWADATE, YASUO; MATSUTANI, TOMOO; HASEGAWA, YUZO; SHINOZAKI, NATSUKI; OIDE, TAKASHI; TANIZAWA, TORU; NAKATANI, YUKIO; SAEKI, NAOKATSU; FUJIMOTO, SHUICHI

    2010-01-01

    The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is limited mainly by O6-methylguanine-DNA methyltransferase (MGMT) expression. The aim of this study was to evaluate the effectiveness of various anticancer drugs for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were administered various anticancer drugs according to drug sensitivity testing. For the individualization, drug-induced apoptosis was quantified by flow cytometry in the primary culture of surgically resected tumor cells. The MGMT protein expression was analyzed by immunohistochemistry. The median survival of the patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9–22.1). The patients with negative MGMT immunostaining had significantly longer survival than those with positive MGMT immunostaining [median survival, 22.3 months (95% CI, 17.6–27.0) vs. 15.1 months (95% CI, 13.4–16.8); p=0.0188]. For MGMT-positive tumors, the platinum agents and the taxanes were more frequently selected for administration than the other categories of anticancer agents. The patient survival period of MGMT-positive glioblastomas treated with the platinum agents or the taxanes [median survival, 20.1 months (95% CI, 18.0–22.7)] was significantly longer than that of MGMT-positive tumors treated with nitrosoureas (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047). These results suggest that the platinum agents and the taxanes offer the best probability to be effective against immunohistochemically MGMT-positive glioblastomas. PMID:23136592

  5. Happy heart, smiling eyes: A systematic review of positive mood effects on broadening of visuospatial attention.

    PubMed

    Vanlessen, Naomi; De Raedt, Rudi; Koster, Ernst H W; Pourtois, Gilles

    2016-09-01

    Positive mood contributes to mental and physical wellbeing. The broaden-and-build theory (Fredrickson, 2001) proposed that the beneficial effects of positive mood on life quality result from attentional broadening. In this article, we systematically review (following PRISMA guidelines; Moher et al., 2009), a host of studies investigating the nature and extent of attentional changes triggered by the experience of positive mood, with a focus on vision. While several studies reported a broadening of attention, others found that positive mood led to a more diffuse information processing style. Positive mood appears to lessen attention selectivity in a way that is context-specific and bound to limitations. We propose a new framework in which we postulate that positive mood impacts the balance between internally and externally directed attention, through modulations of cognitive control processes, instead of broadening attention per se. This novel model is able to accommodate discrepant findings, seeks to translate the phenomenon of the so-called broadening of attention with positive mood into functional terms, and provides plausible neurobiological mechanisms underlying this effect, suggesting a crucial role of the anterior and posterior cingulate cortex in this interaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Controlling for Prior Attainment Reduces the Positive Influence that Single-Gender Classroom Initiatives Exert on High School Students' Scholastic Achievements.

    PubMed

    Pennington, Charlotte R; Kaye, Linda K; Qureshi, Adam W; Heim, Derek

    2018-01-01

    Research points to the positive impact that gender-segregated schooling and classroom initiatives exert on academic attainment. An evaluation of these studies which reveal positive effects highlights, however, that students are typically selectively assigned to single- or mixed-gender instructional settings, presenting a methodological confound. The current study controls for students' prior attainment to appraise the efficacy of a single-gender classroom initiative implemented in a co-educational high school in the United Kingdom. Secondary data analysis (using archived data) was performed on 266 middle-ability, 11-12 year-old students' standardized test scores in Languages (English, foreign language), STEM-related (Mathematics, Science, Information and Communication Technology), and Non-STEM subjects (art, music, drama). Ninety-eight students (54, 55% female) were taught in single-gender and 168 (69, 41% female) in mixed-gender classrooms. Students undertook identical tests irrespective of classroom type, which were graded in accordance with U.K national curriculum guidelines. Controlling for students' prior attainment, findings indicate that students do not appear to benefit from being taught in single-gender relative to mixed-gender classrooms in Language and STEM-related subjects. Young women benefitted from being taught in mixed-gender relative to single-gender classes for Non-STEM subjects. However, when prior ability is not controlled for, the intervention appears to be effective for all school subjects, highlighting the confounding influence of selective admissions. These findings suggest that gender-segregated classroom initiatives may not bolster students' grades. It is argued that studies that do not control for selection effects may tell us little about the effectiveness of such interventions on scholastic achievement.

  7. Processing of Continuously Provided Punishment and Reward in Children with ADHD and the Modulating Effects of Stimulant Medication: An ERP Study

    PubMed Central

    Groen, Yvonne; Tucha, Oliver; Wijers, Albertus A.; Althaus, Monika

    2013-01-01

    Objectives Current models of ADHD suggest abnormal reward and punishment sensitivity, but the exact mechanisms are unclear. This study aims to investigate effects of continuous reward and punishment on the processing of performance feedback in children with ADHD and the modulating effects of stimulant medication. Methods 15 Methylphenidate (Mph)-treated and 15 Mph-free children of the ADHD-combined type and 17 control children performed a selective attention task with three feedback conditions: no-feedback, gain and loss. Event Related Potentials (ERPs) time-locked to feedback and errors were computed. Results All groups performed more accurately with gain and loss than without feedback. Feedback-related ERPs demonstrated no group differences in the feedback P2, but an enhanced late positive potential (LPP) to feedback stimuli (both gains and losses) for Mph-free children with ADHD compared to controls. Feedback-related ERPs in Mph-treated children with ADHD were similar to controls. Correlational analyses in the ADHD groups revealed that the severity of inattention problems correlated negatively with the feedback P2 amplitude and positively with the LPP to losses and omitted gains. Conclusions The early selective attention for rewarding and punishing feedback was relatively intact in children with ADHD, but the late feedback processing was deviant (increased feedback LPP). This may explain the often observed positive effects of continuous reinforcement on performance and behaviour in children with ADHD. However, these group findings cannot be generalised to all individuals with the ADHD, because the feedback-related ERPs were associated with the severity of the inattention problems. Children with ADHD-combined type with more inattention problems showed both deviant early attentional selection of feedback stimuli, and deviant late processing of non-reward and punishment. PMID:23555639

  8. Processing of continuously provided punishment and reward in children with ADHD and the modulating effects of stimulant medication: an ERP study.

    PubMed

    Groen, Yvonne; Tucha, Oliver; Wijers, Albertus A; Althaus, Monika

    2013-01-01

    Current models of ADHD suggest abnormal reward and punishment sensitivity, but the exact mechanisms are unclear. This study aims to investigate effects of continuous reward and punishment on the processing of performance feedback in children with ADHD and the modulating effects of stimulant medication. 15 Methylphenidate (Mph)-treated and 15 Mph-free children of the ADHD-combined type and 17 control children performed a selective attention task with three feedback conditions: no-feedback, gain and loss. Event Related Potentials (ERPs) time-locked to feedback and errors were computed. All groups performed more accurately with gain and loss than without feedback. Feedback-related ERPs demonstrated no group differences in the feedback P2, but an enhanced late positive potential (LPP) to feedback stimuli (both gains and losses) for Mph-free children with ADHD compared to controls. Feedback-related ERPs in Mph-treated children with ADHD were similar to controls. Correlational analyses in the ADHD groups revealed that the severity of inattention problems correlated negatively with the feedback P2 amplitude and positively with the LPP to losses and omitted gains. The early selective attention for rewarding and punishing feedback was relatively intact in children with ADHD, but the late feedback processing was deviant (increased feedback LPP). This may explain the often observed positive effects of continuous reinforcement on performance and behaviour in children with ADHD. However, these group findings cannot be generalised to all individuals with the ADHD, because the feedback-related ERPs were associated with the severity of the inattention problems. Children with ADHD-combined type with more inattention problems showed both deviant early attentional selection of feedback stimuli, and deviant late processing of non-reward and punishment.

  9. Effect of a pelvic wedge and belt on the medial and lateral hamstring muscles during knee flexion.

    PubMed

    Yoo, Won-Gyu

    2017-01-01

    [Purpose] This study developed a pelvic wedge and belt and investigated their effects on the selective activation of medial and lateral hamstring muscles during knee flexion. [Subjects and Methods] Nine adults were enrolled. The participants performed exercises without and with the pelvic wedge and belt, and the electromyographic activities of the medial and lateral hamstring muscles were recorded. [Results] The activity of the medial hamstring was increased significantly when using the pelvic wedge and belt, while the activity of the lateral hamstring did not differ significantly. [Conclusion] The pelvic wedge and belt provide a self-locked position during knee flexion in the prone position. Prone knee flexion in this position is an effective self-exercise for balanced strengthening of the medial hamstring.

  10. Effect of a pelvic wedge and belt on the medial and lateral hamstring muscles during knee flexion

    PubMed Central

    Yoo, Won-gyu

    2017-01-01

    [Purpose] This study developed a pelvic wedge and belt and investigated their effects on the selective activation of medial and lateral hamstring muscles during knee flexion. [Subjects and Methods] Nine adults were enrolled. The participants performed exercises without and with the pelvic wedge and belt, and the electromyographic activities of the medial and lateral hamstring muscles were recorded. [Results] The activity of the medial hamstring was increased significantly when using the pelvic wedge and belt, while the activity of the lateral hamstring did not differ significantly. [Conclusion] The pelvic wedge and belt provide a self-locked position during knee flexion in the prone position. Prone knee flexion in this position is an effective self-exercise for balanced strengthening of the medial hamstring. PMID:28210048

  11. An Examination of the Relative Age Effect in Developmental Girls' Hockey in Ontario

    ERIC Educational Resources Information Center

    Smith, Kristy L.; Weir, Patricia L.

    2013-01-01

    The relative age effect (RAE) suggests that athletes may be provided with greater opportunities for success depending on the position of their birthdate in a sport's selection year. While the effect has been well established in men's sports, less is known about women's sports. This study examined the RAE in developmental girls' hockey in Ontario.…

  12. The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

    PubMed Central

    Bagdas, Deniz; Targowska-Duda, Katarzyna M.; López, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad

    2016-01-01

    BACKGROUND Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective α7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative α7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant induced inflammatory pain, and the chronic constriction injury–induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective α7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid–induced aversion by using the conditioned place aversion test. RESULTS We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by α7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective α7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid induced aversion in the conditioned place aversion assay. CONCLUSIONS These findings suggest that the administration of PAM-2, a new α7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID:26280585

  13. The Evolution of Autistic-Like and Schizotypal Traits: A Sexual Selection Hypothesis

    PubMed Central

    Del Giudice, Marco; Angeleri, Romina; Brizio, Adelina; Elena, Marco R.

    2010-01-01

    In this paper we present a new hypothesis on the evolution of autistic-like and schizotypal personality traits. We argue that autistic-like and schizotypal traits contribute in opposite ways to individual differences in reproductive and mating strategies, and have been maintained – at least in part – by sexual selection through mate choice. Whereas positive schizotypy can be seen as a psychological phenotype oriented to high-mating effort and good genes displays in both sexes, autistic-like traits in their non-pathological form contribute to a male-typical strategy geared toward high parental investment, low-mating effort, and long-term resource allocation. At the evolutionary-genetic level, this sexual selection hypothesis is consistent with Crespi and Badcock's “imprinted brain” theory of autism and psychosis; the effect of offspring mating behavior on resource flow within the family connects sexual selection with genomic imprinting in the context of human biparental care. We conclude by presenting the results of an empirical study testing one of the predictions derived from our hypothesis. In a sample of 199 college students, autistic-like traits predicted lower interest in short-term mating, higher partner-specific investment, and stronger commitment to long-term romantic relations, whereas positive schizotypy showed the opposite pattern of effects. PMID:21833210

  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. Vast Portfolio Selection with Gross-exposure Constraints*

    PubMed Central

    Fan, Jianqing; Zhang, Jingjin; Yu, Ke

    2012-01-01

    We introduce the large portfolio selection using gross-exposure constraints. We show that with gross-exposure constraint the empirically selected optimal portfolios based on estimated covariance matrices have similar performance to the theoretical optimal ones and there is no error accumulation effect from estimation of vast covariance matrices. This gives theoretical justification to the empirical results in Jagannathan and Ma (2003). We also show that the no-short-sale portfolio can be improved by allowing some short positions. The applications to portfolio selection, tracking, and improvements are also addressed. The utility of our new approach is illustrated by simulation and empirical studies on the 100 Fama-French industrial portfolios and the 600 stocks randomly selected from Russell 3000. PMID:23293404

  17. The Effects of Personal Accountability and Personal Responsibility Instruction on Select Off-Task and Positive Social Behaviors

    ERIC Educational Resources Information Center

    Sharpe, Tom; Balderson, Daniel

    2005-01-01

    This study examined the effects of personal accountability and personal responsibility instructional treatments on elementary-age, urban, at-risk physical education students. A multiple treatment (ABAD, ACAD, ADA, control) behavior-analysis design was implemented across four distinct matched class settings to determine the separate and combined…

  18. Influence of Spirituality, Family, and Self Efficacy on Teacher Effectiveness

    ERIC Educational Resources Information Center

    Heffner, Judith Maples

    2016-01-01

    Spirituality, family influence, and teacher efficacy are the focal points of this research project. Research supports family influence as a powerful support in career selection and the positive effects spirituality has on a teacher's personal and professional life. Self efficacy possessed by a teacher gives them an "I can do attitude."…

  19. Selective indication for positive airway pressure (PAP) in sleep-related breathing disorders with obstruction

    PubMed Central

    Stasche, Norbert

    2006-01-01

    Positive airway pressure (PAP) is the therapy of choice for most sleep-related breathing disorders (SRBD). A variety of PAP devices using positive airway pressure (CPAP, BiPAP, APAP, ASV) must be carefully considered before application. This overview aims to provide criteria for choosing the optimal PAP device according to severity and type of sleep-related breathing disorder. In addition, the range of therapeutic applications, constraints and side effects as well as alternative methods to PAP will be discussed. This review is based on an analysis of current literature and clinical experience. The data is presented from an ENT-sleep-laboratory perspective and is designed to help the ENT practitioner initiate treatment and provide support. Different titration methods, current devices and possible applications will be described. In addition to constant pressure devices (CPAP), most commonly used for symptomatic obstructive sleep apnoea (OSA) without complicating conditions, BiPAP models will be introduced. These allow two different positive pressure settings and are thus especially suitable for patients with cardiopulmonary diseases or patients with pressure intolerance, increasing compliance in this subgroup considerably. Compliance can also be increased in patients during first night of therapy, patients with highly variable pressure demands or position-dependent OSA, by using self-regulating Auto-adjust PAP devices (Automatic positive airway pressure, APAP). Patients with Cheyne-Stokes breathing, a subtype of central sleep apnoea, benefit from adaptive servo-ventilation (ASV), which analyzes breathing patterns continually and adjusts the actual ventilation pressure accordingly. This not only reduces daytime sleepiness, but can also influence heart disease positively. Therapy with positive airway pressure is very effective in eliminating obstruction-related sleep diseases and symptoms. However, because therapy is generally applied for life, the optimal PAP device must be carefully selected, taking into account side effects that influence compliance. PMID:22073075

  20. Effects of smoking history on selective attention in schizophrenia.

    PubMed

    Hahn, Constanze; Hahn, Eric; Dettling, Michael; Güntürkün, Onur; Ta, Thi Minh Tam; Neuhaus, Andres H

    2012-03-01

    Smoking prevalence is highly elevated in schizophrenia compared to the general population and to other psychiatric populations. Evidence suggests that smoking may lead to improvements of schizophrenia-associated attention deficits; however, large-scale studies on this important issue are scarce. We examined whether sustained, selective, and executive attention processes are differentially modulated by long-term nicotine consumption in 104 schizophrenia patients and 104 carefully matched healthy controls. A significant interaction of 'smoking status' × 'diagnostic group' was obtained for the domain of selective attention. Smoking was significantly associated with a detrimental conflict effect in controls, while the opposite effect was revealed for schizophrenia patients. Likewise, a positive correlation between a cumulative measure of nicotine consumption and conflict effect in controls and a negative correlation in patients were found. These results provide evidence for specific directional effects of smoking on conflict processing that critically dissociate with diagnosis. The data supports the self-medication hypothesis of smoking in schizophrenia and suggests selective attention as a specific cognitive domain targeted by nicotine consumption. A potential mechanistic model explaining these findings is discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. The effect of alcohol, tobacco and caffeine consumption and vegetarian diet on gallstone prevalence.

    PubMed

    Walcher, Thomas; Haenle, Mark Martin; Mason, Richard Andrew; Koenig, Wolfgang; Imhof, Armin; Kratzer, Wolfgang

    2010-11-01

    To investigate the effects of alcohol, tobacco and caffeine consumption and of vegetarian diet on gallstone prevalence in an urban population sample. A total of 2417 individuals underwent ultrasound examination and completed a standardized questionnaire as part of the EMIL study. Statistical analysis of the data considered the known risk factors of age, female sex, BMI, positive family history and potential confounders, such as alcohol, caffeine and tobacco consumption and vegetarian diet using multiple logistic regression with variable selection. The prevalence of gallstones in the population sample was 8% (171 out of 2147). Findings of the study confirmed the classic risk factors of age, female sex, obesity and positive family history. After the variable selection of potential risk factors in a logistic regression that was adjusted for age, female sex, BMI and positive family history, the factors like tobacco [odds ratio (OR) 1.09, 95% confidence interval (CI): 0.76-1.56, P=0.64] and caffeine consumption (OR: 0.77, 95% CI: 0.42-1.42, P=0.40) as well as vegetarian diet (OR: 1.14, 95% CI: 0.39-3.35, P=0.81) had no effect on gallstone prevalence. A protective effect against development of gallstones was shown for alcohol consumption (OR: 0.67, 95% CI: 0.46-0.99, P=0.04). The factors like tobacco and caffeine consumption as well as vegetarian diet exerted no measurable effect on the prevalence of gallstones. A protective effect was found for alcohol consumption.

  2. Effects of Gene Duplication, Positive Selection, and Shifts in Gene Expression on the Evolution of the Venom Gland Transcriptome in Widow Spiders

    PubMed Central

    Haney, Robert A.; Clarke, Thomas H.; Gadgil, Rujuta; Fitzpatrick, Ryan; Hayashi, Cheryl Y.; Ayoub, Nadia A.; Garb, Jessica E.

    2016-01-01

    Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins. Although these processes have been demonstrated for individual toxin families, high-throughput multitissue sequencing of closely related venomous species can provide insights into evolutionary dynamics at the scale of the entire venom gland transcriptome. By assembling and analyzing multitissue transcriptomes from the Western black widow spider and two closely related species with distinct venom toxicity phenotypes, we do not find that gene duplication and duplicate retention is greater in gene families with venom gland biased expression in comparison with broadly expressed families. Positive selection has acted on some venom toxin families, but does not appear to be in excess for families with venom gland biased expression. Moreover, we find 309 distinct gene families that have single transcripts with venom gland biased expression, suggesting that the switching of genes to venom gland expression in numerous unrelated gene families has been a dominant mode of evolution. We also find ample variation in protein sequences of venom gland–specific transcripts, lineage-specific family sizes, and ortholog expression among species. This variation might contribute to the variable venom toxicity of these species. PMID:26733576

  3. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283.

    PubMed

    Maurer, John J; Sandager-Nielsen, Karin; Schmidt, Heath D

    2017-02-01

    The rewarding and reinforcing effects of nicotine are produced, in large part, by activation of neuronal α4β2* nicotinic acetylcholine receptors (nAChRs), pentameric protein complexes comprised of different stoichiometries of α4 and β2 subunits. However, little is known about the functional role of distinct subtypes of α4β2* nAChRs in nicotine addiction. NS9283 represents a new class of stoichiometry-selective positive allosteric modulators (PAMs) that selectively bind to α4β2 nAChRs containing three α4 and two β2 subunits (3(α4)2(β2) nAChRs). The present experiments were designed to determine the effects of NS9283 on nicotine self-administration and the reinstatement of nicotine-seeking behavior, an animal model of smoking relapse. Parallel studies of sucrose self-administration and reinstatement were conducted in separate cohorts of rats to determine if the effects of NS9283 generalized to other reinforced behaviors. Acute and repeated administration of NS9283 dose-dependently reduced nicotine self-administration and reinstatement in male Sprague Dawley rats. These effects were reinforcer specific as no effects of NS9283 on sucrose self-administration and reinstatement were noted. NS9283 also failed to substitute for nicotine in supporting self-administration behavior suggesting that, at the doses tested, NS9283 alone is not reinforcing. Taken together, these results provide compelling evidence that stoichiometry-selective PAMs of 3(α4)2(β2) nAChRs attenuate nicotine taking and seeking in rats and suggest that targeting 3(α4)2(β2) nAChRs may represent a promising therapeutic strategy for preventing smoking relapse.

  4. [Effects of anxiety and the COMT gene on cortical evoked potentials and performance effectiveness of selective attention].

    PubMed

    Alfimova, M V; Golimbet, V E; Lebedeva, I S; Korovaĭtseva, G I; Lezheĭko, T V

    2014-01-01

    We studied influence of the anxiety-related trait Harm Avoidance and the COMT gene, which is an important modulator of prefrontal functioning, on event-related potentials in oddball paradigm and performance effectiveness of selective attention. For 50 individuals accuracy and time of searching words among letters at any desired rate and then under an instruction to perform the task as quickly and accurate as possible were measured. Scores on the Harm Avoidance scale from Cloninger's Temperament and Character Inventory, N100 and P300 parameters, and COMTVa1158Met genotypes were obtained for them as well. Searching accuracy and time were mainly related to N100 amplitude. The COMT genotype and Harm Avoidance did not affect N100 amplitude; however, the N100 amplitude modulated their effects on accuracy and time dynamics. Harm Avoidance was positively correlated with P300 latency. The results suggest that anxiety and the COMT gene effects on performance effectiveness of selective attention depend on cognitive processes reflected in N100 parameters.

  5. Distinct effects of protracted withdrawal on affect, craving, selective attention and executive functions among alcohol-dependent patients.

    PubMed

    Cordovil De Sousa Uva, Mariana; Luminet, Olivier; Cortesi, Marie; Constant, Eric; Derely, Marc; De Timary, Philippe

    2010-01-01

    The present study examined the effects of protracted alcohol withdrawal on affectivity, craving, selective attention and executive functions (EFs) in alcohol-dependent patients. Selective attention (The D2 Cancellation Test), flexibility (Trail Making Test), inhibition (Stroop Task), decision making (Iowa Gambling Task), craving (Obsessive-Compulsive Drinking Scale) and state affectivity (Positive and Negative Affectivity Schedule) were assessed in alcohol-dependent patients (DSM-IV, n = 35) matched to non-alcohol-dependent participants (n = 22) at the onset (T1: day 1 or 2) and at the end (T2: days 14-18) of protracted withdrawal during rehab. Alcohol-dependent patients' abilities to focus their attention on relevant information, to switch from one pattern to another, to inhibit irrelevant information and to make advantageous choices were lower than those of control participants during both times of a withdrawal cure. No effect of time emerged from analyses for selective attention and EF deficits. Conversely, significant differences between T1 and T2 were observed for craving and affect scores indicating a weakening of alcohol craving and negative affect as well as an improvement of positive affect among patients from onset to the end of cure. Control functions of the Supervisory Attentional System (Norman and Shallice, 1986) were impaired and did not improve during a 3-week withdrawal cure, whereas alcohol craving and negative state affectivity significantly improved in parallel during this period. Implications for understanding the clinical processes of withdrawal are discussed.

  6. Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

    NASA Astrophysics Data System (ADS)

    Huang, Jingtao; Sahin, Mesut; Durand, Dominique M.

    2005-12-01

    The functional effects of selective hypoglossal nerve (HG) stimulation with a multi-contact peripheral nerve electrode were assessed using images of the upper airways and the tongue in anesthetized beagles. A biphasic pulse train of 50 Hz frequency and 2 s duration was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired into a computer. The stimulation current was limited to 20% above the activation threshold for maximum selectivity. The images showed that various contact sets could generate several different activation patterns of the tongue muscles resulting in medial and/or lateral dilation and closing of the airways at the tongue root. Some of these patterns translated into an increase in the oropharyngeal size while others did not have any effect. The pharyngeal sizes were not statistically different during stimulation either between the two different positions of the head (30° and 60°), or when the lateral contacts were compared with the medial ones. The contacts that had the least effect generated an average of 53 ± 15% pharyngeal dilation relative to the best contacts, indicating that the results are marginally sensitive to the contact position around the HG nerve trunk. These results suggest that selective HG nerve stimulation can be a useful technique to produce multiple tongue activation patterns that can dilate the pharynx. This may in turn increase the size of the patient population who can benefit from HG nerve stimulation as a treatment method for obstructive sleep apnea.

  7. Strapped Calix[4]pyrroles Bearing an 1,3-Indanedione at a β-Pyrrolic Position: Chemodosimeters for the Cyanide Anion

    PubMed Central

    Kim, Sook-Hee; Hong, Seong-Jin; Yoo, Jaeduk; Kim, Sung Kuk; Sessler, Janathan L.; Lee, Chang-Hee

    2014-01-01

    A strapped calix[4]pyrrole bearing an 1,3-indanedione group at a β-pyrrolic position has been synthesized and studied as a ratiometric cyanide selective chemosensor. A concentration-dependent bleaching of the initial yellow color was observed upon addition of the cyanide anion. The bleaching, which was observed exclusively with the cyanide anion, occurred even in the presence of other anions. Spectroscopic studies provides support for a mechanistic interpretation wherein the cyanide anion forms a complex with the receptor (K = 2.78 × 104 M-1) through a fast equilibrium, which is followed by slow nucleophilic addition to the β-position of the 1,3-indanedione group. A minimum inhibitory effect from other anions was observed, a feature that could be beneficial in the selective sensing of the cyanide anion. PMID:19639968

  8. Comparison of Several Selective Media for Isolation and Differentiation of Coagulase-Positive Strains of Staphylococcus aureus1

    PubMed Central

    McDivitt, Maxine E.; Topp, Eleanor B.

    1964-01-01

    Six coagulase-positive strains of Staphylococcus aureus which had been cultivated in Brain Heart Infusion broth, milk, and brine were plated on seven isolation media. A significant difference in the growth patterns of the individual strains was found as well as a significant effect resulting from the previous cultivation history before plating. Brine and, to a lesser extent, milk were found to reduce maximal cell concentrations attained, but strains grown in brine and milk showed greater ability to withstand the selective action of the isolation media. Fibrinogen applied to the surface of five of the media allowed the formation of characteristic halos by coagulase-positive strains of S. aureus. Only half of the strains studied produced a zone of precipitation on SM110-Egg Yolk agar. The isolation medium containing cycloheximide and a high level of polymxin B was most inhibitory to the organisms. PMID:14131367

  9. 75 FR 58401 - Government-Owned Inventions; Availability for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ..., attention deficit hyperactivity disorder (ADHD), and schizophrenia. Development of selective pharmacological... Diagnosis of Psychiatric Disorders Description of Invention: Current drugs used to treat schizophrenia block dopamine receptors. These drugs can effectively suppress the ``positive'' symptoms of schizophrenia but...

  10. Whole-Gene Positive Selection, Elevated Synonymous Substitution Rates, Duplication, and Indel Evolution of the Chloroplast clpP1 Gene

    PubMed Central

    Erixon, Per; Oxelman, Bengt

    2008-01-01

    Background Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. Methodology/Principle Findings We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family) and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family). Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying) selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. Conclusions/Significance We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the controversial issue of whether negative or positive selection is to be expected after gene duplications by providing evidence for the latter alternative. The observed increase in synonymous substitution rates in some of the lineages indicates that the detection of positive selection may be obscured under such circumstances. Future studies are required to explore the functional significance of the large inserted repeated amino acid motifs, as well as the possibility that synonymous substitution rates may be affected by positive selection. PMID:18167545

  11. The evolution of multivariate maternal effects.

    PubMed

    Kuijper, Bram; Johnstone, Rufus A; Townley, Stuart

    2014-04-01

    There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations.

  12. The Evolution of Multivariate Maternal Effects

    PubMed Central

    Kuijper, Bram; Johnstone, Rufus A.; Townley, Stuart

    2014-01-01

    There is a growing interest in predicting the social and ecological contexts that favor the evolution of maternal effects. Most predictions focus, however, on maternal effects that affect only a single character, whereas the evolution of maternal effects is poorly understood in the presence of suites of interacting traits. To overcome this, we simulate the evolution of multivariate maternal effects (captured by the matrix M) in a fluctuating environment. We find that the rate of environmental fluctuations has a substantial effect on the properties of M: in slowly changing environments, offspring are selected to have a multivariate phenotype roughly similar to the maternal phenotype, so that M is characterized by positive dominant eigenvalues; by contrast, rapidly changing environments favor Ms with dominant eigenvalues that are negative, as offspring favor a phenotype which substantially differs from the maternal phenotype. Moreover, when fluctuating selection on one maternal character is temporally delayed relative to selection on other traits, we find a striking pattern of cross-trait maternal effects in which maternal characters influence not only the same character in offspring, but also other offspring characters. Additionally, when selection on one character contains more stochastic noise relative to selection on other traits, large cross-trait maternal effects evolve from those maternal traits that experience the smallest amounts of noise. The presence of these cross-trait maternal effects shows that individual maternal effects cannot be studied in isolation, and that their study in a multivariate context may provide important insights about the nature of past selection. Our results call for more studies that measure multivariate maternal effects in wild populations. PMID:24722346

  13. Are medication restrictions before FOBT necessary?

    PubMed Central

    Konrad, Gerald; Katz, Alan

    2012-01-01

    Abstract Objective To determine whether medication interventions enhance the sensitivity and specificity of guaiac-based fecal occult blood testing (FOBT) when screening for colorectal cancer (CRC). Data sources We searched PubMed-MEDLINE, CINAHL, and the Cochrane databases using the MeSH headings occult blood, feces/analysis, and guaiac/analysis, linking them to variations of anticoagulants, heparin, warfarin, iron, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, cyclooxygenase-2 inhibitors, and ascorbic acid (vitamin C). Study selections were limited to English studies involving humans. Study selection All resulting titles and abstracts were reviewed for studies that included manipulation of medications associated with guaiac-based FOBT. If the study’s relevance was unclear from the abstract, the full article was reviewed. The search resulted in 31 pertinent studies. Synthesis No studies addressed the effects of medication interventions on the sensitivity or specificity of FOBT screening. Randomized controlled trials, however, showed no increase in the rate of positive results among those taking NSAIDs. The literature is mixed regarding the effect of NSAIDs on the positive predictive value of a positive FOBT result, although no change in positive predictive value has been shown for warfarin. Iron will not affect FOBT results in vivo. Ascorbic acid might inhibit positive FOBT results both in vitro and in vivo, but it has not been studied in screening populations. Conclusion Studies evaluating the effects of medication intervention on FOBT screening for CRC are limited by their lower quality and because they do not address sensitivity and specificity. Available evidence, however, does not suggest a benefit from withholding NSAIDs, anticoagulant medications, or iron during the screening period. These recommendations should be abandoned in order to maximize adherence to screening. Positive FOBT results obtained among patients taking these medications deserve full evaluation for CRC. Until further studies clarify the effect of ascorbic acid on FOBT screening, withholding this medication before testing seems prudent. PMID:22972722

  14. Environmental and genetic effects on weight and visual score traits at postweaning in Suffolk sheep.

    PubMed

    Nascimento, Bárbara Mazetti; Somavilla, Adriana Luiza; Dias, Laila Talarico; Teixeira, Rodrigo de Almeida

    2014-10-01

    This study aimed to investigate the following environmental effects in Suffolk lambing: contemporary groups, type of birth, and age of animal and age of dam at lambing on conformation (C), precocity (P), musculature (M), and body weight at postweaning (W), and the heritability coefficients and genetic correlations among these traits. Contemporary groups, type of birth, and age of animal and age of dam at lambing were significant for W. For C, all the effects studied were significant, except linear and quadratic effects of age of the animal. For P, all effects studied were significant, except the quadratic effect of age of the animal. For M, the effects of contemporary group, type of birth, and the linear effect of the age of the animal were significant. Heritability estimates were 0.07 ± 0.03, 0.14 ± 0.03, 0.09 ± 0.03, and 0.11 ± 0.03 for C, P, M, and W, respectively, indicating a positive low response for direct selection. Estimates of genetic correlations among the visual scores (C, P, and M) and W were moderate to highly favorable and positive, ranging from 0.48 to 0.90. These results indicate that selection for visual scores will increase body weight.

  15. Mechanism for and method of biasing magnetic sensor

    DOEpatents

    Kautz, David R.

    2007-12-04

    A magnetic sensor package having a biasing mechanism involving a coil-generated, resistor-controlled magnetic field for providing a desired biasing effect. In a preferred illustrated embodiment, the package broadly comprises a substrate; a magnetic sensor element; a biasing mechanism, including a coil and a first resistance element; an amplification mechanism; a filter capacitor element; and an encapsulant. The sensor is positioned within the coil. A current applied to the coil produces a biasing magnetic field. The biasing magnetic field is controlled by selecting a resistance value for the first resistance element which achieves the desired biasing effect. The first resistance element preferably includes a plurality of selectable resistors, the selection of one or more of which sets the resistance value.

  16. Relative age effect and performance in the U16, U18 and U20 European Basketball Championships.

    PubMed

    Arrieta, Haritz; Torres-Unda, Jon; Gil, Susana María; Irazusta, Jon

    2016-08-01

    This study sought to determine the association of relative age and performance of young elite basketball players. The distribution of the birth dates, heights, positions, classification and performance of the male and female participants (n = 2395) of the U16, U18 and U20 European Basketball Championships were analysed. We found an over-representation of players born during the initial months of the year in all groups, with the relative age effect being more evident in players of the U16 and U18 groups, than of the U20 teams, particularly in male squads. Nevertheless, in the U20 championships, those teams that had the oldest players performed the best. In all championships, the oldest participants played more minutes. In addition, relatively older male players scored better in total points and in performance index rating when results were normalised to played time. This effect was not found for female players. Regarding playing position, different distributions of birth dates were observed due to each position's physical requirements. Thus, basketball coaches and managers should keep these results in mind when they select players because if not, they might subject players who are born towards the end of the year to a negative selection bias.

  17. Music-induced positive mood broadens the scope of auditory attention

    PubMed Central

    Makkonen, Tommi; Eerola, Tuomas

    2017-01-01

    Abstract Previous studies indicate that positive mood broadens the scope of visual attention, which can manifest as heightened distractibility. We used event-related potentials (ERP) to investigate whether music-induced positive mood has comparable effects on selective attention in the auditory domain. Subjects listened to experimenter-selected happy, neutral or sad instrumental music and afterwards participated in a dichotic listening task. Distractor sounds in the unattended channel elicited responses related to early sound encoding (N1/MMN) and bottom-up attention capture (P3a) while target sounds in the attended channel elicited a response related to top-down-controlled processing of task-relevant stimuli (P3b). For the subjects in a happy mood, the N1/MMN responses to the distractor sounds were enlarged while the P3b elicited by the target sounds was diminished. Behaviorally, these subjects tended to show heightened error rates on target trials following the distractor sounds. Thus, the ERP and behavioral results indicate that the subjects in a happy mood allocated their attentional resources more diffusely across the attended and the to-be-ignored channels. Therefore, the current study extends previous research on the effects of mood on visual attention and indicates that even unfamiliar instrumental music can broaden the scope of auditory attention via its effects on mood. PMID:28460035

  18. Cryotherapy and Joint Position Sense in Healthy Participants: A Systematic Review

    PubMed Central

    Costello, Joseph T.; Donnelly, Alan E.

    2010-01-01

    Abstract Objective: To (1) search the English-language literature for original research addressing the effect of cryotherapy on joint position sense (JPS) and (2) make recommendations regarding how soon healthy athletes can safely return to participation after cryotherapy. Data Sources: We performed an exhaustive search for original research using the AMED, CINAHL, MEDLINE, and SportDiscus databases from 1973 to 2009 to gather information on cryotherapy and JPS. Key words used were cryotherapy and proprioception, cryotherapy and joint position sense, cryotherapy, and proprioception. Study Selection: The inclusion criteria were (1) the literature was written in English, (2) participants were human, (3) an outcome measure included JPS, (4) participants were healthy, and (5) participants were tested immediately after a cryotherapy application to a joint. Data Extraction: The means and SDs of the JPS outcome measures were extracted and used to estimate the effect size (Cohen d) and associated 95% confidence intervals for comparisons of JPS before and after a cryotherapy treatment. The numbers, ages, and sexes of participants in all 7 selected studies were also extracted. Data Synthesis: The JPS was assessed in 3 joints: ankle (n  =  2), knee (n  =  3), and shoulder (n  =  2). The average effect size for the 7 included studies was modest, with effect sizes ranging from −0.08 to 1.17, with a positive number representing an increase in JPS error. The average methodologic score of the included studies was 5.4/10 (range, 5–6) on the Physiotherapy Evidence Database scale. Conclusions: Limited and equivocal evidence is available to address the effect of cryotherapy on proprioception in the form of JPS. Until further evidence is provided, clinicians should be cautious when returning individuals to tasks requiring components of proprioceptive input immediately after a cryotherapy treatment. PMID:20446845

  19. Positive versus negative framing of a hypothetical infant immunization: the influence of involvement.

    PubMed

    Donovan, R J; Jalleh, G

    2000-02-01

    Framing studies dealing with health messages show mixed results, although a tendency in favor of negative framing. Involvement has been hypothesized to account for these conflicting results. The authors selected a realistic issue (immunization of infants) deemed high or low involving depending on the respondent's circumstances: women with an infant or who were pregnant or intending to get pregnant in the next 12 months were deemed to be high involved; women in none of these categories were deemed to be low involved. A convenience sample of adult women was presented with a hypothetical "new" immunization that protected infants against respiratory complaints such as bronchitis and pneumonia Side effects (the common flu) were framed positively (90% chance of no side effects) or negatively (10% chance of side effects). The authors found positive framing to be superior for low-involved respondents, but there was no framing effect for high-involved respondents.

  20. 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.

  1. 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

  2. Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

    PubMed

    van Hooft, Pim; Greyling, Ben J; Getz, Wayne M; van Helden, Paul D; Zwaan, Bas J; Bastos, Armanda D S

    2014-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important implications for our understanding not only of the evolutionary and ecological dynamics of sex-ratio distorters and suppressors, but also of the functioning of deleterious and sexually-antagonistic alleles, and their impact on population viability.

  3. Rejection or selection: influence of framing in investment decisions.

    PubMed

    Cheng, Pi-Yueh; Chiou, Wen-Bin

    2010-02-01

    According to prospect theory, reflection effects result in preferences for risk-averse choices in gain situations and risk-seeking choices in loss situations. However, relevant literature in regard to decision making has suggested that positive information receives more weight in a selection task, whereas negative information receives more weight in a rejection task. The present study examined whether the nature of a decision task (selection vs rejection) would moderate the reflection effects. Undergraduates (47 men, 49 women; M age = 20.5 yr., SD = 1.1), selected according to specific screening criteria, participated in an experimental study. Typical reflection effects were observed in both selection and rejection task conditions. More importantly, negative information (i.e., the information about probable loss in risky choice of gain situations and the information about certain loss in cautious choice of loss situations) provided in the context of a rejection task received more weight and resulted in more frequent endorsements of the cautious choice in gain situations and of the risky choice in loss situations. Hence, the findings suggest that a decision context characterized by rejection may expand the reflection effects and thereby provide important information about situations in which investment decisions occur in a context characterized by rejection.

  4. Genomic Characterization of Variable Surface Antigens Reveals a Telomere Position Effect as a Prerequisite for RNA Interference-Mediated Silencing in Paramecium tetraurelia

    PubMed Central

    Baranasic, Damir; Oppermann, Timo; Cheaib, Miriam; Cullum, John; Schmidt, Helmut

    2014-01-01

    ABSTRACT Antigenic or phenotypic variation is a widespread phenomenon of expression of variable surface protein coats on eukaryotic microbes. To clarify the mechanism behind mutually exclusive gene expression, we characterized the genetic properties of the surface antigen multigene family in the ciliate Paramecium tetraurelia and the epigenetic factors controlling expression and silencing. Genome analysis indicated that the multigene family consists of intrachromosomal and subtelomeric genes; both classes apparently derive from different gene duplication events: whole-genome and intrachromosomal duplication. Expression analysis provides evidence for telomere position effects, because only subtelomeric genes follow mutually exclusive transcription. Microarray analysis of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to serotype-pure wild-type cultures, shows cotranscription of a subset of subtelomeric genes, indicating that the telomere position effect is due to a selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We present a model of surface antigen evolution by intrachromosomal gene duplication involving the maintenance of positive selection of structurally relevant regions. Further analysis of chromosome heterogeneity shows that alternative telomere addition regions clearly affect transcription of closely related genes. Consequently, chromosome fragmentation appears to be of crucial importance for surface antigen expression and evolution. Our data suggest that RNAi-mediated control of this genetic network by trans-acting RNAs allows rapid epigenetic adaptation by phenotypic variation in combination with long-term genetic adaptation by Darwinian evolution of antigen genes. PMID:25389173

  5. The Design and Development of a Potent and Selective Novel Diprolyl Derivative That Binds to the N-Domain of Angiotensin-I Converting Enzyme.

    PubMed

    Fienberg, Stephen; Cozier, Gyles E; Acharya, K Ravi; Chibale, Kelly; Sturrock, Edward D

    2018-01-11

    Angiotensin-I converting enzyme (ACE) is a zinc metalloprotease consisting of two catalytic domains (N- and C-). Most clinical ACE inhibitor(s) (ACEi) have been shown to inhibit both domains nonselectively, resulting in adverse effects such as cough and angioedema. Selectively inhibiting the individual domains is likely to reduce these effects and potentially treat fibrosis in addition to hypertension. ACEi from the GVK Biosciences database were inspected for possible N-domain selective binding patterns. From this set, a diprolyl chemical series was modeled using docking simulations. The series was expanded based on key target interactions involving residues known to impart N-domain selectivity. In total, seven diprolyl compounds were synthesized and tested for N-domain selective ACE inhibition. One compound with an aspartic acid in the P 2 position (compound 16) displayed potent inhibition (K i = 11.45 nM) and was 84-fold more selective toward the N-domain. A high-resolution crystal structure of compound 16 in complex with the N-domain revealed the molecular basis for the observed selectivity.

  6. The Effects of Direct Mail Appeals on Awareness, Readership, and Cognitive Response Content in a Community Heart Health Campaign.

    ERIC Educational Resources Information Center

    Loken, Barbara; And Others

    A study was conducted to determine the effectiveness of direct mail appeals in a heart health campaign and to explore the effects of three appeal types (positive, negative, and informational) on knowledge levels and behavior patterns. Seven-hundred fifty randomly selected households were mailed brochures representing one of the three appeal types.…

  7. Effects of particle size distribution in thick film conductors

    NASA Technical Reports Server (NTRS)

    Vest, R. W.

    1983-01-01

    Studies of particle size distribution in thick film conductors are discussed. The distribution of particle sizes does have an effect on fired film density but the effect is not always positive. A proper distribution of sizes is necessary, and while the theoretical models can serve as guides to selecting this proper distribution, improved densities can be achieved by empirical variations from the predictions of the models.

  8. Longitudinal investigation on learned helplessness tested under negative and positive reinforcement involving stimulus control.

    PubMed

    Oliveira, Emileane C; Hunziker, Maria Helena

    2014-07-01

    In this study, we investigated whether (a) animals demonstrating the learned helplessness effect during an escape contingency also show learning deficits under positive reinforcement contingencies involving stimulus control and (b) the exposure to positive reinforcement contingencies eliminates the learned helplessness effect under an escape contingency. Rats were initially exposed to controllable (C), uncontrollable (U) or no (N) shocks. After 24h, they were exposed to 60 escapable shocks delivered in a shuttlebox. In the following phase, we selected from each group the four subjects that presented the most typical group pattern: no escape learning (learned helplessness effect) in Group U and escape learning in Groups C and N. All subjects were then exposed to two phases, the (1) positive reinforcement for lever pressing under a multiple FR/Extinction schedule and (2) a re-test under negative reinforcement (escape). A fourth group (n=4) was exposed only to the positive reinforcement sessions. All subjects showed discrimination learning under multiple schedule. In the escape re-test, the learned helplessness effect was maintained for three of the animals in Group U. These results suggest that the learned helplessness effect did not extend to discriminative behavior that is positively reinforced and that the learned helplessness effect did not revert for most subjects after exposure to positive reinforcement. We discuss some theoretical implications as related to learned helplessness as an effect restricted to aversive contingencies and to the absence of reversion after positive reinforcement. This article is part of a Special Issue entitled: insert SI title. Copyright © 2014. Published by Elsevier B.V.

  9. Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

    PubMed

    Aird, Steven D; Aggarwal, Shikha; Villar-Briones, Alejandro; Tin, Mandy Man-Ying; Terada, Kouki; Mikheyev, Alexander S

    2015-08-28

    While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown. Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation. Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

  10. 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.

  11. PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes.

    PubMed

    Su, Fei; Ou, Hong-Yu; Tao, Fei; Tang, Hongzhi; Xu, Ping

    2013-12-27

    With genomic sequences of many closely related bacterial strains made available by deep sequencing, it is now possible to investigate trends in prokaryotic microevolution. Positive selection is a sub-process of microevolution, in which a particular mutation is favored, causing the allele frequency to continuously shift in one direction. Wide scanning of prokaryotic genomes has shown that positive selection at the molecular level is much more frequent than expected. Genes with significant positive selection may play key roles in bacterial adaption to different environmental pressures. However, selection pressure analyses are computationally intensive and awkward to configure. Here we describe an open access web server, which is designated as PSP (Positive Selection analysis for Prokaryotic genomes) for performing evolutionary analysis on orthologous coding genes, specially designed for rapid comparison of dozens of closely related prokaryotic genomes. Remarkably, PSP facilitates functional exploration at the multiple levels by assignments and enrichments of KO, GO or COG terms. To illustrate this user-friendly tool, we analyzed Escherichia coli and Bacillus cereus genomes and found that several genes, which play key roles in human infection and antibiotic resistance, show significant evidence of positive selection. PSP is freely available to all users without any login requirement at: http://db-mml.sjtu.edu.cn/PSP/. PSP ultimately allows researchers to do genome-scale analysis for evolutionary selection across multiple prokaryotic genomes rapidly and easily, and identify the genes undergoing positive selection, which may play key roles in the interactions of host-pathogen and/or environmental adaptation.

  12. Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection.

    PubMed

    Costello, Patrick S; Nicolas, Robert H; Watanabe, Yasuyuki; Rosewell, Ian; Treisman, Richard

    2004-03-01

    Thymocyte selection and differentiation requires extracellular signal-regulated kinase (Erk) signaling, but transcription factor substrates of Erk in thymocytes are unknown. We have characterized the function of SAP-1 (Elk4), an Erk-regulated transcription factor, in thymocyte development. Early thymocyte development was normal, but single-positive thymocyte and peripheral T cell numbers were reduced, reflecting a T cell-autonomous defect. T cell receptor-induced activation of SAP-1 target genes such as Egr1 was substantially impaired in double-positive thymocytes, although Erk activation was normal. Analysis of T cell receptor transgenes showed that positive selection was reduced by 80-90% in SAP-1-deficient mice; heterozygous mice showed a moderate defect. Negative selection was unimpaired. SAP-1 thus directly links Erk signaling to the transcriptional events required for thymocyte positive selection.

  13. Collaboration and Conflict Resolution in Education.

    ERIC Educational Resources Information Center

    Melamed, James C.; Reiman, John W.

    2000-01-01

    Presents guidelines for resolving conflicts between educators and parents. Participants should seek different perspectives, not "truths," consider the common ground, define an effective problem-solving procedure, adopt ground rules for discussion, address issues, identify interests and positive intentions, develop options, select arrangements, and…

  14. 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

  15. Prediction-Oriented Marker Selection (PROMISE): With Application to High-Dimensional Regression.

    PubMed

    Kim, Soyeon; Baladandayuthapani, Veerabhadran; Lee, J Jack

    2017-06-01

    In personalized medicine, biomarkers are used to select therapies with the highest likelihood of success based on an individual patient's biomarker/genomic profile. Two goals are to choose important biomarkers that accurately predict treatment outcomes and to cull unimportant biomarkers to reduce the cost of biological and clinical verifications. These goals are challenging due to the high dimensionality of genomic data. Variable selection methods based on penalized regression (e.g., the lasso and elastic net) have yielded promising results. However, selecting the right amount of penalization is critical to simultaneously achieving these two goals. Standard approaches based on cross-validation (CV) typically provide high prediction accuracy with high true positive rates but at the cost of too many false positives. Alternatively, stability selection (SS) controls the number of false positives, but at the cost of yielding too few true positives. To circumvent these issues, we propose prediction-oriented marker selection (PROMISE), which combines SS with CV to conflate the advantages of both methods. Our application of PROMISE with the lasso and elastic net in data analysis shows that, compared to CV, PROMISE produces sparse solutions, few false positives, and small type I + type II error, and maintains good prediction accuracy, with a marginal decrease in the true positive rates. Compared to SS, PROMISE offers better prediction accuracy and true positive rates. In summary, PROMISE can be applied in many fields to select regularization parameters when the goals are to minimize false positives and maximize prediction accuracy.

  16. Selection on parental performance opposes selection for larger body mass in a wild population of blue tits.

    PubMed

    Thomson, Caroline E; Bayer, Florian; Crouch, Nicholas; Farrell, Samantha; Heap, Elizabeth; Mittell, Elizabeth; Zurita-Cassinello, Mar; Hadfield, Jarrod D

    2017-03-01

    There is abundant evidence in many taxa for positive directional selection on body size, and yet little evidence for microevolutionary change. In many species, variation in body size is partly determined by the actions of parents, so a proposed explanation for stasis is the presence of a negative genetic correlation between direct and parental effects. Consequently, selecting genes for increased body size would result in a correlated decline in parental effects, reducing body size in the following generation. We show that these arguments implicitly assume that parental care is cost free, and that including a cost alters the predicted genetic architectures needed to explain stasis. Using a large cross-fostered population of blue tits, we estimate direct selection on parental effects for body mass, and show it is negative. Negative selection is consistent with a cost to parental care, mainly acting through a reduction in current fecundity rather than survival. Under these conditions, evolutionary stasis is possible for moderately negative genetic correlations between direct and parental effects. This is in contrast to the implausibly extreme correlations needed when care is assumed to be cost-free. Thus, we highlight the importance of accounting correctly for complete selection acting on traits across generations. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  17. A group's physical attractiveness is greater than the average attractiveness of its members: the group attractiveness effect.

    PubMed

    van Osch, Yvette; Blanken, Irene; Meijs, Maartje H J; van Wolferen, Job

    2015-04-01

    We tested whether the perceived physical attractiveness of a group is greater than the average attractiveness of its members. In nine studies, we find evidence for the so-called group attractiveness effect (GA-effect), using female, male, and mixed-gender groups, indicating that group impressions of physical attractiveness are more positive than the average ratings of the group members. A meta-analysis on 33 comparisons reveals that the effect is medium to large (Cohen's d = 0.60) and moderated by group size. We explored two explanations for the GA-effect: (a) selective attention to attractive group members, and (b) the Gestalt principle of similarity. The results of our studies are in favor of the selective attention account: People selectively attend to the most attractive members of a group and their attractiveness has a greater influence on the evaluation of the group. © 2015 by the Society for Personality and Social Psychology, Inc.

  18. Determinants and Impact of Rural-Urban Migration: A Case Study of Selected Communities in Western Nigeria. African Rural Employment Paper No. 10.

    ERIC Educational Resources Information Center

    Essang, Sunday M.; Mabawonku, Adewale F.

    This economic analysis of migration was designed to test the following six hypotheses on the causes of out-migration from agriculture and its effect on the rural economy of Western Nigeria: (1) age of the rural family, of which the migrant is a member, is positively related to rural-urban migration rate; (2) a positive relationship exists between…

  19. Characterizing the effects of amplitude, frequency and limb position on vibration induced movement illusions: Implications in sensory-motor rehabilitation

    PubMed Central

    Schofield, Jonathon S.; Dawson, Michael R.; Carey, Jason P.; Hebert, Jacqueline S.

    2015-01-01

    BACKGROUND Strategic vibration of musculotendinous regions of a limb elicits illusionary sensations of movement. As a rehabilitation technique, this ‘kinesthetic illusion’ has demonstrated beneficial results for numerous sensory-motor disorders. However, literature shows little consistency in the vibration parameters or body positioning used, and their effects have yet to be comprehensively investigated. OBJECTIVE To characterize the effects of the vibration amplitude, frequency, and limb position on the kinesthetic illusion. METHODS Movement illusions were induced in 12 participants’ biceps and triceps. The effect of amplitude (0.1 to 0.5 mm), frequency (70 to 110 Hz), and two limb positions were quantified on the strength of illusion (SOI), range of motion (ROM) and velocity. RESULTS Amplitude significantly affected the illusionary SOI, ROM and velocity in the biceps and triceps (p < 0.05). Increasing amplitude resulted in an increase of all three output variables. Limb position showed an effect on illusionary velocity in the biceps as well as ROM and velocity in the triceps (p < 0.05). Frequency demonstrated no statistical effect. CONCLUSIONS Amplitude demonstrated the most profound impact on the kinesthetic illusion in the experimental ranges tested. This work may help guide clinicians and researchers in selecting appropriate vibratory parameters and body positions to consistently elicit and manipulate the kinesthetic illusion. PMID:25425585

  20. Effect of nonsinusoidal bias waveforms on ion energy distributions and fluorocarbon plasma etch selectivity

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

    Agarwal, Ankur; Kushner, Mark J.; Iowa State University, Department of Electrical and Computer Engineering, 104 Marston Hall, Ames, Iowa 50011-2151

    2005-09-15

    The distributions of ion energies incident on the wafer significantly influence feature profiles and selectivity during plasma etching. Control of ion energies is typically obtained by varying the amplitude or frequency of a radio frequency sinusoidal bias voltage applied to the substrate. The resulting ion energy distribution (IED), though, is generally broad. Controlling the width and shape of the IED can potentially improve etch selectivity by distinguishing between threshold energies of surface processes. In this article, control of the IED was computationally investigated by applying a tailored, nonsinusoidal bias waveform to the substrate of an inductively coupled plasma. The waveformmore » we investigated, a quasi-dc negative bias having a short positive pulse each cycle, produced a narrow IED whose width was controllable based on the length of the positive spike and frequency. We found that the selectivity between etching Si and SiO{sub 2} in fluorocarbon plasmas could be controlled by adjusting the width and energy of the IED. Control of the energy of a narrow IED enables etching recipes that transition between speed and selectivity without change of gas mixture.« less

  1. 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.

  2. Polarizing the Nazarov cyclization: the impact of dienone substitution pattern on reactivity and selectivity.

    PubMed

    He, Wei; Herrick, Ildiko R; Atesin, Tulay A; Caruana, Patrick A; Kellenberger, Colleen A; Frontier, Alison J

    2008-01-23

    The impact of dienone substitution on the Nazarov cyclization has been examined in detail. Substrates bearing different substituents at each of four positions on the dienone backbone were systematically probed in order to identify trends leading to higher reactivity and better selectivity. Desymmetrization of the pentadienyl cation and oxyallyl cation intermediates through placement of polarizing groups at both the C-2 and C-4 positions was found to be particularly effective. These modifications allowed cyclizations to occur in the presence of catalytic amounts of mild Lewis acids. It was also found that stereoconvergent cyclization of mixtures of E and Z isomers of alkylidene beta-ketoesters occurred via an efficient isomerization process that occurred under the reaction conditions.

  3. Detecting Past Positive Selection through Ongoing Negative Selection

    PubMed Central

    Bazykin, Georgii A.; Kondrashov, Alexey S.

    2011-01-01

    Detecting positive selection is a challenging task. We propose a method for detecting past positive selection through ongoing negative selection, based on comparison of the parameters of intraspecies polymorphism at functionally important and selectively neutral sites where a nucleotide substitution of the same kind occurred recently. Reduced occurrence of recently replaced ancestral alleles at functionally important sites indicates that negative selection currently acts against these alleles and, therefore, that their replacements were driven by positive selection. Application of this method to the Drosophila melanogaster lineage shows that the fraction of adaptive amino acid replacements remained approximately 0.5 for a long time. In the Homo sapiens lineage, however, this fraction drops from approximately 0.5 before the Ponginae–Homininae divergence to approximately 0 after it. The proposed method is based on essentially the same data as the McDonald–Kreitman test but is free from some of its limitations, which may open new opportunities, especially when many genotypes within a species are known. PMID:21859804

  4. Using variable rate models to identify genes under selection in sequence pairs: their validity and limitations for EST sequences.

    PubMed

    Church, Sheri A; Livingstone, Kevin; Lai, Zhao; Kozik, Alexander; Knapp, Steven J; Michelmore, Richard W; Rieseberg, Loren H

    2007-02-01

    Using likelihood-based variable selection models, we determined if positive selection was acting on 523 EST sequence pairs from two lineages of sunflower and lettuce. Variable rate models are generally not used for comparisons of sequence pairs due to the limited information and the inaccuracy of estimates of specific substitution rates. However, previous studies have shown that the likelihood ratio test (LRT) is reliable for detecting positive selection, even with low numbers of sequences. These analyses identified 56 genes that show a signature of selection, of which 75% were not identified by simpler models that average selection across codons. Subsequent mapping studies in sunflower show four of five of the positively selected genes identified by these methods mapped to domestication QTLs. We discuss the validity and limitations of using variable rate models for comparisons of sequence pairs, as well as the limitations of using ESTs for identification of positively selected genes.

  5. The glass cliff: when and why women are selected as leaders in crisis contexts.

    PubMed

    Bruckmüller, Susanne; Branscombe, Nyla R

    2010-09-01

    The glass cliff refers to women being more likely to rise to positions of organizational leadership in times of crisis than in times of success, and men being more likely to achieve those positions in prosperous times. We examine the role that (a) a gendered history of leadership and (b) stereotypes about gender and leadership play in creating the glass cliff. In Expt 1, participants who read about a company with a male history of leadership selected a male future leader for a successful organization, but chose a female future leader in times of crisis. This interaction--between company performance and gender of the preferred future leader--was eliminated for a counter-stereotypic history of female leadership. In Expt 2, stereotypically male attributes were most predictive of leader selection in a successful organization, while stereotypically female attributes were most predictive in times of crisis. Differences in the endorsement of these stereotypes, in particular with regard to the ascription of lower stereotypically female attributes to the male candidate mediated the glass cliff effect. Overall, results suggest that stereotypes about male leadership may be more important for the glass cliff effect than stereotypes about women and leadership.

  6. Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates.

    PubMed

    Greenberg, Tsafrir; Carlson, Joshua M; Rubin, Denis; Cha, Jiook; Mujica-Parodi, Lilianne

    2015-04-01

    The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, 'uncertain' (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of 'uncertain' clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. The Influence of HIV on the Evolution of Mycobacterium tuberculosis

    PubMed Central

    Brites, Daniela; Stucki, David; Evans, Joanna C.; Seldon, Ronnett; Heekes, Alexa; Mulder, Nicola; Nicol, Mark; Oni, Tolu; Mizrahi, Valerie; Warner, Digby F.; Parkhill, Julian; Gagneux, Sebastien; Martin, Darren P.; Wilkinson, Robert J.

    2017-01-01

    Abstract HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates. PMID:28369607

  8. Stearoyl-acyl carrier protein desaturases are associated with floral isolation in sexually deceptive orchids

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

    Schluter, P.M.; Shanklin, J.; Xu, S.

    The orchids Ophrys sphegodes and O. exaltata are reproductively isolated from each other by the attraction of two different, highly specific pollinator species. For pollinator attraction, flowers chemically mimic the pollinators sex pheromones, the key components of which are alkenes with different double-bond positions. This study identifies genes likely involved in alkene biosynthesis, encoding stearoyl-acyl carrier protein (ACP) desaturase (SAD) homologs. The expression of two isoforms, SAD1 and SAD2, is flower-specific and broadly parallels alkene production during flower development. SAD2 shows a significant association with alkene production, and in vitro assays show that O. sphegodes SAD2 has activity both asmore » an 18:0-ACP {Delta}{sup 9} and a 16:0-ACP {Delta}{sup 4} desaturase. Downstream metabolism of the SAD2 reaction products would give rise to alkenes with double-bonds at position 9 or position 12, matching double-bond positions observed in alkenes in the odor bouquet of O. sphegodes. SAD1 and SAD2 show evidence of purifying selection before, and positive or relaxed purifying selection after gene duplication. By contributing to the production of species-specific alkene bouquets, SAD2 is suggested to contribute to differential pollinator attraction and reproductive isolation among these species. Taken together, these data are consistent with the hypothesis that SAD2 is a florally expressed barrier gene of large phenotypic effect and, possibly, a genic target of pollinator-mediated selection.« less

  9. Stearoyl-acyl carrier protein desaturases are associated with floral isolation in sexually deceptive orchids

    PubMed Central

    Schlüter, Philipp M.; Xu, Shuqing; Gagliardini, Valeria; Whittle, Edward; Shanklin, John; Grossniklaus, Ueli; Schiestl, Florian P.

    2011-01-01

    The orchids Ophrys sphegodes and O. exaltata are reproductively isolated from each other by the attraction of two different, highly specific pollinator species. For pollinator attraction, flowers chemically mimic the pollinators’ sex pheromones, the key components of which are alkenes with different double-bond positions. This study identifies genes likely involved in alkene biosynthesis, encoding stearoyl-acyl carrier protein (ACP) desaturase (SAD) homologs. The expression of two isoforms, SAD1 and SAD2, is flower-specific and broadly parallels alkene production during flower development. SAD2 shows a significant association with alkene production, and in vitro assays show that O. sphegodes SAD2 has activity both as an 18:0-ACP Δ9 and a 16:0-ACP Δ4 desaturase. Downstream metabolism of the SAD2 reaction products would give rise to alkenes with double-bonds at position 9 or position 12, matching double-bond positions observed in alkenes in the odor bouquet of O. sphegodes. SAD1 and SAD2 show evidence of purifying selection before, and positive or relaxed purifying selection after gene duplication. By contributing to the production of species-specific alkene bouquets, SAD2 is suggested to contribute to differential pollinator attraction and reproductive isolation among these species. Taken together, these data are consistent with the hypothesis that SAD2 is a florally expressed barrier gene of large phenotypic effect and, possibly, a genic target of pollinator-mediated selection. PMID:21436056

  10. Fear of negative evaluation biases social evaluation inference: evidence from a probabilistic learning task.

    PubMed

    Button, Katherine S; Kounali, Daphne; Stapinski, Lexine; Rapee, Ronald M; Lewis, Glyn; Munafò, Marcus R

    2015-01-01

    Fear of negative evaluation (FNE) defines social anxiety yet the process of inferring social evaluation, and its potential role in maintaining social anxiety, is poorly understood. We developed an instrumental learning task to model social evaluation learning, predicting that FNE would specifically bias learning about the self but not others. During six test blocks (3 self-referential, 3 other-referential), participants (n = 100) met six personas and selected a word from a positive/negative pair to finish their social evaluation sentences "I think [you are / George is]…". Feedback contingencies corresponded to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5 and 0.2, respectively. As FNE increased participants selected fewer positive words (β = -0.4, 95% CI -0.7, -0.2, p = 0.001), which was strongest in the self-referential condition (FNE × condition 0.28, 95% CI 0.01, 0.54, p = 0.04), and the neutral and dislike rules (FNE × condition × rule, p = 0.07). At low FNE the proportion of positive words selected for self-neutral and self-disliked greatly exceeded the feedback contingency, indicating poor learning, which improved as FNE increased. FNE is associated with differences in processing social-evaluative information specifically about the self. At low FNE this manifests as insensitivity to learning negative self-referential evaluation. High FNE individuals are equally sensitive to learning positive or negative evaluation, which although objectively more accurate, may have detrimental effects on mental health.

  11. Limited utility of residue masking for positive-selection inference.

    PubMed

    Spielman, Stephanie J; Dawson, Eric T; Wilke, Claus O

    2014-09-01

    Errors in multiple sequence alignments (MSAs) can reduce accuracy in positive-selection inference. Therefore, it has been suggested to filter MSAs before conducting further analyses. One widely used filter, Guidance, allows users to remove MSA positions aligned with low confidence. However, Guidance's utility in positive-selection inference has been disputed in the literature. We have conducted an extensive simulation-based study to characterize fully how Guidance impacts positive-selection inference, specifically for protein-coding sequences of realistic divergence levels. We also investigated whether novel scoring algorithms, which phylogenetically corrected confidence scores, and a new gap-penalization score-normalization scheme improved Guidance's performance. We found that no filter, including original Guidance, consistently benefitted positive-selection inferences. Moreover, all improvements detected were exceedingly minimal, and in certain circumstances, Guidance-based filters worsened inferences. © The Author 2014. 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.

  12. Lateralized goal framing: how selective presentation impacts message effectiveness.

    PubMed

    McCormick, Michael; Seta, John J

    2012-11-01

    We tested whether framing a message as a gain or loss would alter its effectiveness by using a dichotic listening procedure to selectively present a health related message to the left or right hemisphere. A significant goal framing effect (losses > gains) was found when right, but not left, hemisphere processing was initially enhanced. The results support the position that the contextual processing style of the right hemisphere is especially sensitive to the associative implications of the frame. We discussed the implications of these findings for goal framing research, and the valence hypothesis. We also discussed how these findings converge with prior valence framing research and how they can be of potential use to health care providers.

  13. Effects of the GABAB Receptor-Positive Modulators CGP7930 and rac-BHFF in Baclofen- and γ-Hydroxybutyrate-Discriminating Pigeons

    PubMed Central

    France, Charles P.; Cheng, Kejun; Rice, Kenner C.

    2012-01-01

    In vivo effects of GABAB receptor-positive modulators suggest them to have therapeutic potential to treat central nervous system disorders such as anxiety and drug abuse. Although these effects are thought to be mediated by positive modulation of GABAB receptors, such modulation has been examined primarily in vitro. This study further examined the in vivo properties of the GABAB receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF). In pigeons discriminating baclofen from saline, γ-hydroxybutyrate (GHB) produced 100% baclofen-appropriate responding, and the GABAB antagonist 3-aminopropyl(dimethoxymethyl) phosphinic acid (CGP35348) blocked the effects of both drugs. CGP7930 and rac-BHFF produced at most 41 and 74% baclofen-appropriate responding, respectively, and enhanced the discriminative stimulus effects of baclofen, but not of GHB. In pigeons discriminating GHB from saline, CGP7930 and rac-BHFF produced at most 1 and 49% GHB-appropriate responding, respectively, and enhanced the effects of baclofen, but not of GHB. Enhancement of the discriminative stimulus effects of baclofen by rac-BHFF and CGP7930 is further evidence of their effectiveness as GABAB receptor-positive modulators in vivo. Furthermore, lack of complete substitution of the positive modulators rac-BHFF and CGP7930 for baclofen and GHB suggests that their discriminative stimulus effects differ from those of GABAB receptor agonists. Finally, together with converging evidence that the GABAB receptor populations mediating the effects of baclofen and GHB are not identical, the present findings suggest that these populations differ in their susceptibility to positive modulatory effects. Such differences could allow for more selective therapeutic targeting of the GABAB system. PMID:22319197

  14. The effect of artificial selection on phenotypic plasticity in maize.

    PubMed

    Gage, Joseph L; Jarquin, Diego; Romay, Cinta; Lorenz, Aaron; Buckler, Edward S; Kaeppler, Shawn; Alkhalifah, Naser; Bohn, Martin; Campbell, Darwin A; Edwards, Jode; Ertl, David; Flint-Garcia, Sherry; Gardiner, Jack; Good, Byron; Hirsch, Candice N; Holland, Jim; Hooker, David C; Knoll, Joseph; Kolkman, Judith; Kruger, Greg; Lauter, Nick; Lawrence-Dill, Carolyn J; Lee, Elizabeth; Lynch, Jonathan; Murray, Seth C; Nelson, Rebecca; Petzoldt, Jane; Rocheford, Torbert; Schnable, James; Schnable, Patrick S; Scully, Brian; Smith, Margaret; Springer, Nathan M; Srinivasan, Srikant; Walton, Renee; Weldekidan, Teclemariam; Wisser, Randall J; Xu, Wenwei; Yu, Jianming; de Leon, Natalia

    2017-11-07

    Remarkable productivity has been achieved in crop species through artificial selection and adaptation to modern agronomic practices. Whether intensive selection has changed the ability of improved cultivars to maintain high productivity across variable environments is unknown. Understanding the genetic control of phenotypic plasticity and genotype by environment (G × E) interaction will enhance crop performance predictions across diverse environments. Here we use data generated from the Genomes to Fields (G2F) Maize G × E project to assess the effect of selection on G × E variation and characterize polymorphisms associated with plasticity. Genomic regions putatively selected during modern temperate maize breeding explain less variability for yield G × E than unselected regions, indicating that improvement by breeding may have reduced G × E of modern temperate cultivars. Trends in genomic position of variants associated with stability reveal fewer genic associations and enrichment of variants 0-5000 base pairs upstream of genes, hypothetically due to control of plasticity by short-range regulatory elements.

  15. Probability of success for phase III after exploratory biomarker analysis in phase II.

    PubMed

    Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

    2017-05-01

    The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

  16. The effects of negative and positive mood induction on eating behaviour: A meta-analysis of laboratory studies in the healthy population and eating and weight disorders.

    PubMed

    Cardi, Valentina; Leppanen, Jenni; Treasure, Janet

    2015-10-01

    The aim of this study was to conduct a meta-analysis to quantify the effect of induced negative and positive mood on meal consumption in healthy participants and patients with eating and weight disorders. The search term "MOOD" was combined with the following keywords: "TEST MEAL" or "LABORATORY FEEDING" or "LABORATORY MEAL" or "TASTE TEST" or "TASTE TASK" to identify the relevant studies. Thirty-three studies were selected, including 2491 participants. Two meta-analyses compared negative mood or positive mood with neutral mood. Induced negative mood was significantly associated with greater food intake, especially in restrained eaters and binge eaters. Positive mood was also associated with greater caloric intake across groups. These findings support the causal relationship between negative mood and greater food intake, especially in restrained eaters and binge eaters. Preliminary evidence indicates that strategies to improve positive mood might be of benefit for people with anorexia nervosa and bulimia nervosa, although the size of the effect across a single meal is small. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Brain Responses to Emotional Images Related to Cognitive Ability in Older Adults

    PubMed Central

    Foster, Shannon M.; Davis, Hasker P.; Kisley, Michael A.

    2013-01-01

    Older adults have been shown to exhibit a positivity effect in processing of emotional stimuli, seemingly focusing more on positive than negative information. Whether this reflects purposeful changes or an unintended side-effect of declining cognitive abilities is unclear. For the present study older adults displaying a wide range of cognitive abilities completed measures of attention, visual and verbal memory, executive functioning, and processing speed, as well as a socioemotional measure of time perspective. Regression analyses examined the ability of these variables to predict neural responsivity to select emotional stimuli as measured with the late positive potential (LPP), an event-related brain potential (ERP). Stronger cognitive functioning was associated with higher LPP amplitude in response to negative images (i.e., greater processing). This does not support a voluntary avoidance of negative information processing in older adults for this particular measure of attentional allocation. A model is proposed to reconcile this finding with the extant literature that has demonstrated positivity effects in measures of later, controlled attentional allocation. PMID:23276213

  18. Salmon's Laws.

    ERIC Educational Resources Information Center

    Shannon, Thomas A.

    1994-01-01

    Presents Paul Salmon's old-fashioned, common-sense guidelines for success in practical school administration. The maxims advise on problem ownership; the value of selective neglect; the importance of empowerment, enthusiasm, and effective communication; and the need for positive reinforcement, cultivation of support, and good relations with media,…

  19. Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.

    PubMed

    Hall, Peter S; McCabe, Christopher; Stein, Robert C; Cameron, David

    2012-01-04

    Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer. We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research. The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups. There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data.

  20. The effect of morphometric atlas selection on multi-atlas-based automatic brachial plexus segmentation.

    PubMed

    Van de Velde, Joris; Wouters, Johan; Vercauteren, Tom; De Gersem, Werner; Achten, Eric; De Neve, Wilfried; Van Hoof, Tom

    2015-12-23

    The present study aimed to measure the effect of a morphometric atlas selection strategy on the accuracy of multi-atlas-based BP autosegmentation using the commercially available software package ADMIRE® and to determine the optimal number of selected atlases to use. Autosegmentation accuracy was measured by comparing all generated automatic BP segmentations with anatomically validated gold standard segmentations that were developed using cadavers. Twelve cadaver computed tomography (CT) atlases were included in the study. One atlas was selected as a patient in ADMIRE®, and multi-atlas-based BP autosegmentation was first performed with a group of morphometrically preselected atlases. In this group, the atlases were selected on the basis of similarity in the shoulder protraction position with the patient. The number of selected atlases used started at two and increased up to eight. Subsequently, a group of randomly chosen, non-selected atlases were taken. In this second group, every possible combination of 2 to 8 random atlases was used for multi-atlas-based BP autosegmentation. For both groups, the average Dice similarity coefficient (DSC), Jaccard index (JI) and Inclusion index (INI) were calculated, measuring the similarity of the generated automatic BP segmentations and the gold standard segmentation. Similarity indices of both groups were compared using an independent sample t-test, and the optimal number of selected atlases was investigated using an equivalence trial. For each number of atlases, average similarity indices of the morphometrically selected atlas group were significantly higher than the random group (p < 0,05). In this study, the highest similarity indices were achieved using multi-atlas autosegmentation with 6 selected atlases (average DSC = 0,598; average JI = 0,434; average INI = 0,733). Morphometric atlas selection on the basis of the protraction position of the patient significantly improves multi-atlas-based BP autosegmentation accuracy. In this study, the optimal number of selected atlases used was six, but for definitive conclusions about the optimal number of atlases and to improve the autosegmentation accuracy for clinical use, more atlases need to be included.

  1. Tilted seat position for non-ambulant individuals with neurological and neuromuscular impairment: a systematic review.

    PubMed

    Michael, S M; Porter, D; Pountney, T E

    2007-12-01

    To determine the effects of tilt-in-space seating on outcomes for people with neurological or neuromuscular impairment who cannot walk. Search through electronic databases (MEDLINE, Embase, CINAHL, AMED). Discussions with researchers who are active in field. Selection criteria included interventional studies that investigated the effects of seat tilt on outcome or observational studies that identified outcomes for those who had used tilt-in-space seating in populations with neurological or neuromuscular impairments. Two reviewers independently selected trials for inclusion, assessed quality and extracted data. Nineteen studies were identified which fulfilled the selection criteria. Seventeen of these were essentially before-after studies investigating the immediate effects of tilting the seating. All studies looked at populations with neurological impairment, and most were on children with cerebral palsy (n=8) or adults with spinal cord injury (n=8). REVIEWER'S CONCLUSION: Posterior tilt can reduce pressures at the interface under the pelvis.

  2. Pilot selection and training

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Personality and situational factors relevant to individual and group performance in highly demanding environments, such as those faced by astronauts or by jet transport crew, are discussed. It is emphasized that although technical competence and proficiency in pilot selection are prerequisites for safety, operating a modern jet transport is a group endeavor that requires the effective coordination of the entire crew. A self-report test battery for measuring positive and negative personality traits of pilot candidates, termed the Personal Characteristics Inventory, is described.

  3. Dynamic Optical Filtration

    NASA Technical Reports Server (NTRS)

    Chretien, Jean-Loup (Inventor); Lu, Edward T. (Inventor)

    2005-01-01

    A dynamic optical filtration system and method effectively blocks bright light sources without impairing view of the remainder of the scene. A sensor measures light intensity and position so that selected cells of a shading matrix may interrupt the view of the bright light source by a receptor. A beamsplitter may be used so that the sensor may be located away from the receptor. The shading matrix may also be replaced by a digital micromirror device, which selectively sends image data to the receptor.

  4. Dynamic optical filtration

    NASA Technical Reports Server (NTRS)

    Chretien, Jean-Loup (Inventor); Lu, Edward T. (Inventor)

    2005-01-01

    A dynamic optical filtration system and method effectively blocks bright light sources without impairing view of the remainder of the scene. A sensor measures light intensity and position so that selected cells of a shading matrix may interrupt the view of the bright light source by a receptor. A beamsplitter may be used so that the sensor may be located away from the receptor. The shading matrix may also be replaced by a digital micromirror device, which selectively sends image data to the receptor.

  5. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence.

    PubMed

    Bosch-Capblanch, Xavier; Marceau, Claudine

    2014-12-01

    To describe the training, supervision and quality of care components of integrated Community Case Management (iCCM) programmes and to draw lessons learned from existing evaluations of those programmes. Scoping review of reports from 29 selected iCCM programmes purposively provided by stakeholders containing any information relevant to understand quality of care issues. The number of people reached by iCCM programmes varied from the tens of thousands to more than a million. All programmes aimed at improving access of vulnerable populations to health care, focusing on the main childhood illnesses, managed by Community Health Workers (CHW), often selected bycommunities. Training and supervision were widely implemented, in different ways and intensities, and often complemented with tools (eg, guides, job aids), supplies, equipment and incentives. Quality of care was measured using many outcomes (eg, access or appropriate treatment). Overall, there seemed to be positive effects for those strategies that involved policy change, organisational change, standardisation of clinical practices and alignment with other programmes. Positive effects were mostly achieved in large multi-component programmes. Mild or no effects have been described on mortality reduction amongst the few programmes for which data on this outcome was available to us. Promising strategies included teaming-up of CHW, micro-franchising or social franchising. On-site training and supervision of CHW have been shown to improve clinical practices. Effects on caregivers seemed positive, with increases in knowledge, care seeking behaviour, or caregivers' basic disease management. Evidence on iCCM is often of low quality, cannot relate specific interventions or the ways they are implemented with outcomes and lacks standardisation; this limits the capacity to identify promising strategies to improve quality of care. Large, multi-faceted, iCCM programmes, with strong components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations.

  6. Molecular evolution of respiratory syncytial virus subgroup A genotype NA1 and ON1 attachment glycoprotein (G) gene in central Vietnam.

    PubMed

    Yoshihara, Keisuke; Le, Minh Nhat; Nagasawa, Koo; Tsukagoshi, Hiroyuki; Nguyen, Hien Anh; Toizumi, Michiko; Moriuchi, Hiroyuki; Hashizume, Masahiro; Ariyoshi, Koya; Dang, Duc Anh; Kimura, Hirokazu; Yoshida, Lay-Myint

    2016-11-01

    We performed molecular evolutionary analyses of the G gene C-terminal 3rd hypervariable region of RSV-A genotypes NA1 and ON1 strains from the paediatric acute respiratory infection patients in central Vietnam during the 2010-2012 study period. Time-scaled phylogenetic analyses were performed using Bayesian Markov Chain Monte Carlo (MCMC) method, and pairwise distances (p-distances) were calculated. Bayesian Skyline Plot (BSP) was constructed to analyze the time-trend relative genetic diversity of central Vietnam RSV-A strains. We also estimated the N-glycosylation sites within G gene hypervariable region. Amino acid substitutions under positive and negative selection pressure were examined using Conservative Single Likelihood Ancestor Counting (SLAC), Fixed Effects Likelihood (FEL), Internal Fixed Effects Likelihood (IFEL) and Mixed Effects Model for Episodic Diversifying Selection (MEME) models. The majority of central Vietnam ON1 strains detected in 2012 were classified into lineage 1 with few positively selected substitutions. As for the Vietnamese NA1 strains, four lineages were circulating during the study period with a few positive selection sites. Shifting patterns of the predominantly circulating NA1 lineage were observed in each year during the investigation period. Median p-distance of central Vietnam NA1 strains was wider (p-distance=0.028) than that of ON1 (p-distance=0.012). The molecular evolutionary rate of central Vietnam ON1 strains was estimated to be 2.55×10 -2 (substitutions/site/year) and was faster than NA1 (7.12×10 -3 (substitutions/site/year)). Interestingly, the evolutionary rates of both genotypes ON1 and NA1 strains from central Vietnam were faster than the global strains respectively. Furthermore, the shifts of N-glycosylation pattern within the G gene 3rd hypervariable region of Vietnamese NA1 strains were observed in each year. BSP analysis indicated the rapid growth of RSV-A effective population size in early 2012. These results suggested that the molecular evolution of RSV-A G gene detected in central Vietnam was fast with unique evolutionary dynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence

    PubMed Central

    Bosch–Capblanch, Xavier; Marceau, Claudine

    2014-01-01

    Aim To describe the training, supervision and quality of care components of integrated Community Case Management (iCCM) programmes and to draw lessons learned from existing evaluations of those programmes. Methods Scoping review of reports from 29 selected iCCM programmes purposively provided by stakeholders containing any information relevant to understand quality of care issues. Results The number of people reached by iCCM programmes varied from the tens of thousands to more than a million. All programmes aimed at improving access of vulnerable populations to health care, focusing on the main childhood illnesses, managed by Community Health Workers (CHW), often selected bycommunities. Training and supervision were widely implemented, in different ways and intensities, and often complemented with tools (eg, guides, job aids), supplies, equipment and incentives. Quality of care was measured using many outcomes (eg, access or appropriate treatment). Overall, there seemed to be positive effects for those strategies that involved policy change, organisational change, standardisation of clinical practices and alignment with other programmes. Positive effects were mostly achieved in large multi–component programmes. Mild or no effects have been described on mortality reduction amongst the few programmes for which data on this outcome was available to us. Promising strategies included teaming–up of CHW, micro–franchising or social franchising. On–site training and supervision of CHW have been shown to improve clinical practices. Effects on caregivers seemed positive, with increases in knowledge, care seeking behaviour, or caregivers’ basic disease management. Evidence on iCCM is often of low quality, cannot relate specific interventions or the ways they are implemented with outcomes and lacks standardisation; this limits the capacity to identify promising strategies to improve quality of care. Conclusion Large, multi–faceted, iCCM programmes, with strong components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations. PMID:25520793

  8. Perceived duration of emotional events: evidence for a positivity effect in older adults.

    PubMed

    Nicol, Jeffrey R; Tanner, Jessica; Clarke, Kelly

    2013-01-01

    BACKGROUND/STUDY CONTEXT: Arousal and negative affect modulate the effect of emotion on the subjective experience of the passage of time. Given that older adults are less aroused by negative emotional stimuli, and report lower levels of negative affect, compared with younger adults, the present study examined whether the effect of emotion on time perception differed in older and younger adults. Participants performed a temporal bisection task for emotional (i.e., angry, sad, happy) and neutral facial expressions presented at varying temporal intervals. Older adults perceived the duration of both positive and threatening events longer than neutral events, whereas younger adults only perceived threatening events longer than neutral events. The results, which are partially consistent with the positivity effect of aging postulated by the socioemotional selectivity theory, are the first to show how the effect of emotion on perceived duration affects older adults, and support previous research indicating that only threatening events prolong perceived duration in younger adults.

  9. Automatic Omega Station and LOP (Line of Position) Selection,

    DTIC Science & Technology

    1987-09-01

    LL- jAj C) LJ b- I- I LL I-0 a- 5~52 3.2.2 SOLAR EFFECTS The sun effects Omega modal interference in several significant ways. Firstly the effect...nx(n+l) TD and F are 2x(n+l) -67- %..T C ..4 . (43). a -Je MT Therefore to form BTH requires 4n multiplies and (H TH)- 1 requires 6 multiplies and

  10. Rational design of antimicrobial C3a analogues with enhanced effects against Staphylococci using an integrated structure and function-based approach.

    PubMed

    Pasupuleti, Mukesh; Walse, Björn; Svensson, Bo; Malmsten, Martin; Schmidtchen, Artur

    2008-09-02

    The anaphylatoxin C3a and its inactivated derivative C3adesArg, generated during complement activation, exert direct antimicrobial effects, mediated via its C-terminal region [Nordahl et al. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 16879-16884]. During evolution, this region of C3a displays subtle changes in net charge, while preserving a moderate but variable amphipathicity [Pasupuleti et al. (2007) J. Biol. Chem. 282, 2520-2528]. In this study, we mimic these evolutionary changes, employing a design approach utilizing selected amino acid substitutions at strategic and structurally relevant positions in the original human C3a peptide CNYITELRRQHARASHLGLA, followed by structure-activity studies incorporating sequence-dependent QSAR models as tools for generation of C3a peptide variants with enhanced effects. While the native peptide and related amphipathic analogues of moderate positive net charge were active against the Gram-negative Escherichia coli, activity against the Gram-positive Staphylococcus aureus was primarily observed for peptides characterized by a combination of a relatively high net charge (+6-7) and a propensity to adopt an alpha-helical conformation with amphipathic character. Such increased helicity and charge also conferred activity against the fungus Candida albicans. A central histidine residue (H11), evolutionarily conserved among vertebrates, conferred high selectivity toward microbes, while substitutions with leucine rendered the peptides hemolytic. Selected C3a analogues retained their specificity against staphylococci in the presence of human plasma, while showing low cytotoxicity. The work illustrates structure-activity relationships underlying the function and specificity of antimicrobial C3a and related analogues and provides insights into the forces that drive evolution of antimicrobial peptides.

  11. Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2015-11-17

    Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent. In this study, we used an in vivo competition assay in mice immunised with ACV and in naïve (control) mice to compare the proportion of colonisation with recent clinical Prn positive and Prn negative B. pertussis strains from Australia. The Prn negative strain colonised the respiratory tract more effectively than the Prn positive strain in immunised mice, out-competing the Prn positive strain by day 3 of infection. However, in control mice, the Prn positive strain out-competed the Prn negative strain. Our findings of greater ability of Prn negative strains to colonise ACV-immunised mice are consistent with reports of selective advantage for these strains in ACV-immunised humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance.

    PubMed

    Jann, Oliver C; Werling, Dirk; Chang, Jung-Su; Haig, David; Glass, Elizabeth J

    2008-10-20

    There is accumulating evidence that polymorphism in Toll-like receptor (TLR) genes might be associated with disease resistance or susceptibility traits in livestock. Polymorphic sites affecting TLR function should exhibit signatures of positive selection, identified as a high ratio of non-synonymous to synonymous nucleotide substitutions (omega). Phylogeny based models of codon substitution based on estimates of omega for each amino acid position can therefore offer a valuable tool to predict sites of functional relevance. We have used this approach to identify such polymorphic sites within the bovine TLR2 genes from ten Bos indicus and Bos taurus cattle breeds. By analysing TLR2 gene phylogeny in a set of mammalian species and a subset of ruminant species we have estimated the selective pressure on individual sites and domains and identified polymorphisms at sites of putative functional importance. The omega were highest in the mammalian TLR2 domains thought to be responsible for ligand binding and lowest in regions responsible for heterodimerisation with other TLR-related molecules. Several positively-selected sites were detected in or around ligand-binding domains. However a comparison of the ruminant subset of TLR2 sequences with the whole mammalian set of sequences revealed that there has been less selective pressure among ruminants than in mammals as a whole. This suggests that there have been functional changes during ruminant evolution. Twenty newly-discovered non-synonymous polymorphic sites were identified in cattle. Three of them were localised at positions shaped by positive selection in the ruminant dataset (Leu227Phe, His305Pro, His326Gln) and in domains involved in the recognition of ligands. His326Gln is of particular interest as it consists of an exchange of differentially-charged amino acids at a position which has previously been shown to be crucial for ligand binding in human TLR2. Within bovine TLR2, polymorphisms at amino acid positions 227, 305 and 326 map to functionally important sites of TLR2 and should be considered as candidate SNPs for immune related traits in cattle. A final proof of their functional relevance requires further studies to determine their functional effect on the immune response after stimulation with relevant ligands and/or their association with immune related traits in animals.

  13. Selection of Phototransduction Genes in Homo sapiens.

    PubMed

    Christopher, Mark; Scheetz, Todd E; Mullins, Robert F; Abràmoff, Michael D

    2013-08-13

    We investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level. SNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively. Six of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes. There is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.

  14. Analytic theory for the selection of Saffman-Taylor fingers in the presence of thin film effects

    NASA Technical Reports Server (NTRS)

    Tanveer, S.

    1989-01-01

    An analytic theory is presented for the width selection of Saffman-Taylor fingers in the presence of thin film effect. In the limit of small capillary number Ca and small gap to width ratio epsilon, such that epsilon much less than Ca much less than 1, it is found that fingers with relative width lambda less than 1/2 are possible such that lambda squared (1-lambda)/(1-2 lambda) = k epsilon/Ca(sup 3/2), where the positive constant k depends on the branch of solution and equals 2.776 for the first branch. A fully nonlinear analysis is necessary in this problem even to obtain the correct scaling law. It is also shown how in principle, the selection rule for arbitrary Ca can be obtained.

  15. Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin with Current Modulation

    PubMed Central

    Hagen, Joshua A.; Kim, Sang N.; Bayraktaroglu, Burhan; Leedy, Kevin; Chávez, Jorge L.; Kelley-Loughnane, Nancy; Naik, Rajesh R.; Stone, Morley O.

    2011-01-01

    Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3′ terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels. PMID:22163977

  16. Integrating fluoroquinolones into the hospital formulary.

    PubMed

    Bertino, J S

    2001-10-01

    With the increasing availability of new agents, selection of fluoroquinolones for formulary inclusion can be difficult. Appropriate evaluation of the important characteristics (pharmacokinetic and pharmacodynamic properties, antimicrobial activity, efficacy, tolerability, cost) of these agents should allow selection of the most cost-effective ones. Evidence from in vitro studies and clinical trials indicates differences exist among fluoroquinolones, especially in terms of activity against gram-positive, aerobic organisms. For selected clinical situations, it may be important to choose an agent that is available in both intravenous and oral formulations. Comparative drug costs, as well as costs associated with potential clinical failure and adverse events, should be evaluated carefully. Dosage regimens should be considered, as shorter durations of therapy and less frequent dose administration may lead to reduced labor costs and increased patient compliance, thereby improving effectiveness and economic efficiency.

  17. Effect of increased HoxB4 on human megakaryocytic development

    PubMed Central

    Zhong, Yiming; Sullenbarger, Brent; Lasky, Larry C.

    2010-01-01

    In order to ex vivo produce clinically useful quantity of platelets, we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data indicate that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord blood cells primarily by upregulating Tpo R and Fli-1 expression and downregulating c-Myb expression. Increasing HoxB4 expression or adding recombinant HoxB4 protein might be a way to expand Mks for the production of platelets for use in transfusion medicine. PMID:20599537

  18. Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

    PubMed

    Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

    2014-05-01

    Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

  19. Phylogeny and evolution of Newcastle disease virus genotypes isolated in Asia during 2008-2011.

    PubMed

    Ebrahimi, Mohammad Majid; Shahsavandi, Shahla; Moazenijula, Gholamreza; Shamsara, Mahdi

    2012-08-01

    The full-length fusion (F) genes of 51 Newcastle disease (ND) strains isolated from chickens in Asia during the period 2008-2011 were genetically analyzed. Phylogenetic analysis showed that genotype VII of NDV still predominant in the domestic poultry of Asia. The sub-genotype VIIb circulated in the Iran and Indian sub-continent countries, whereas VIId sub-genotype existed in Far East countries. The non-synonymous to synonymous substitutions ratio was calculated 0.27 for VIId sub-genotype and 0.51 for VIIb sub-genotype indicates purifying/stabilizing selection which resulted in a low evolution rate in F gene of VIIb sub-genotype. There is evidence of localized positive selection when comparing these sub-genotypes protein sequences. Five codons in F gene of ND viruses had a posterior probability >90% using the Bayesian method, indicating these sites were under positive selection. To identify sites under positive selection; amino acid substitution classified depends on their radicalism and neutrality. The results indicate that although most positions were under purifying selection and can be eliminated, a few positions located in sub-genotype specific regions were subject to positive selection.

  20. Selfing ability and dispersal are positively related, but not affected by range position: a multispecies study on southern African Asteraceae.

    PubMed

    de Waal, C; Rodger, J G; Anderson, B; Ellis, A G

    2014-05-01

    Dispersal and breeding system traits are thought to affect colonization success. As species have attained their present distribution ranges through colonization, these traits may vary geographically. Although several theories predict associations between dispersal ability, selfing ability and the relative position of a population within its geographic range, there is little theoretical or empirical consensus on exactly how these three variables are related. We investigated relationships between dispersal ability, selfing ability and range position across 28 populations of 13 annual, wind-dispersed Asteraceae species from the Namaqualand region of South Africa. Controlling for phylogeny, relative dispersal ability--assessed from vertical fall time of fruits--was positively related to an index of autofertility--determined from hand-pollination experiments. These findings support the existence of two discrete syndromes: high selfing ability associated with good dispersal and obligate outcrossing associated with lower dispersal ability. This is consistent with the hypothesis that selection for colonization success drives the evolution of an association between these traits. However, no general effect of range position on dispersal or breeding system traits was evident. This suggests selection on both breeding system and dispersal traits acts consistently across distribution ranges. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  1. Some Effects of School Building Renovation on Pupil Attitudes and Behavior in Selected Junior High Schools.

    ERIC Educational Resources Information Center

    Cramer, Robert Joseph

    A study of 2,300 junior high school students from three schools determined the effect of a newly renovated school, a new school environment, and an old dilapidated school environment on their attitudes and behavior. Points were assigned to their answers; high scores indicated a positive attitude. Results show attitudes were lowest in the old…

  2. Sensory Modality and Stimulus Control in the Pigeon: Cross-Species Generality of Single-Incentive Selective-Association Effects

    ERIC Educational Resources Information Center

    Panlilio, Leigh V.; Weiss, Stanley J.

    2005-01-01

    In earlier studies with rats, the effectiveness of the auditory element of a tone--light discriminative stimulus was enhanced when the conditioned incentive value of the compound was negative rather than positive. The present experiment systematically replicated these results in pigeons trained to press a treadle in the presence of a tone--light…

  3. Synthesis, activity and pharmacophore development for isatin-β-thiosemicarbazones with selective activity towards multidrug resistant cellsa

    PubMed Central

    Hall, Matthew D.; Salam, Noeris K.; Hellawell, Jennifer L.; Fales, Henry M.; Kensler, Caroline B.; Ludwig, Joseph A.; Szakacs, Gergely; Hibbs, David E.; Gottesman, Michael M.

    2009-01-01

    We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β-thiosemicarbazones from our initial study have been validated, and a range of analogs synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1-selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone, and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicty of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity, and aid in directing the search for the mechanism of action of 1. PMID:19397322

  4. To kill, stay or flee: the effects of lions and landscape factors on habitat and kill site selection of cheetahs in South Africa.

    PubMed

    Rostro-García, Susana; Kamler, Jan F; Hunter, Luke T B

    2015-01-01

    Understanding how animals utilize available space is important for their conservation, as it provides insight into the ecological needs of the species, including those related to habitat, prey and inter and intraspecific interactions. We used 28 months of radio telemetry data and information from 200 kill locations to assess habitat selection at the 3rd order (selection of habitats within home ranges) and 4th order (selection of kill sites within the habitats used) of a reintroduced population of cheetahs Acinonyx jubatus in Phinda Private Game Reserve, South Africa. Along with landscape characteristics, we investigated if lion Panthera leo presence affected habitat selection of cheetahs. Our results indicated that cheetah habitat selection was driven by a trade-off between resource acquisition and lion avoidance, and the balance of this trade-off varied with scale: more open habitats with high prey densities were positively selected within home ranges, whereas more closed habitats with low prey densities were positively selected for kill sites. We also showed that habitat selection, feeding ecology, and avoidance of lions differed depending on the sex and reproductive status of cheetahs. The results highlight the importance of scale when investigating a species' habitat selection. We conclude that the adaptability of cheetahs, together with the habitat heterogeneity found within Phinda, explained their success in this small fenced reserve. The results provide information for the conservation and management of this threatened species, especially with regards to reintroduction efforts in South Africa.

  5. To Kill, Stay or Flee: The Effects of Lions and Landscape Factors on Habitat and Kill Site Selection of Cheetahs in South Africa

    PubMed Central

    Rostro-García, Susana; Kamler, Jan F.; Hunter, Luke T. B.

    2015-01-01

    Understanding how animals utilize available space is important for their conservation, as it provides insight into the ecological needs of the species, including those related to habitat, prey and inter and intraspecific interactions. We used 28 months of radio telemetry data and information from 200 kill locations to assess habitat selection at the 3rd order (selection of habitats within home ranges) and 4th order (selection of kill sites within the habitats used) of a reintroduced population of cheetahs Acinonyx jubatus in Phinda Private Game Reserve, South Africa. Along with landscape characteristics, we investigated if lion Panthera leo presence affected habitat selection of cheetahs. Our results indicated that cheetah habitat selection was driven by a trade-off between resource acquisition and lion avoidance, and the balance of this trade-off varied with scale: more open habitats with high prey densities were positively selected within home ranges, whereas more closed habitats with low prey densities were positively selected for kill sites. We also showed that habitat selection, feeding ecology, and avoidance of lions differed depending on the sex and reproductive status of cheetahs. The results highlight the importance of scale when investigating a species’ habitat selection. We conclude that the adaptability of cheetahs, together with the habitat heterogeneity found within Phinda, explained their success in this small fenced reserve. The results provide information for the conservation and management of this threatened species, especially with regards to reintroduction efforts in South Africa. PMID:25693067

  6. Evolution of Genes Involved in Gamete Interaction: Evidence for Positive Selection, Duplications and Losses in Vertebrates

    PubMed Central

    Callebaut, Isabelle; Laurin, Michel; Pascal, Géraldine; Poupon, Anne; Goudet, Ghylène; Monget, Philippe

    2012-01-01

    Genes encoding proteins involved in sperm-egg interaction and fertilization exhibit a particularly fast evolution and may participate in prezygotic species isolation [1], [2]. Some of them (ZP3, ADAM1, ADAM2, ACR and CD9) have individually been shown to evolve under positive selection [3], [4], suggesting a role of positive Darwinian selection on sperm-egg interaction. However, the genes involved in this biological function have not been systematically and exhaustively studied with an evolutionary perspective, in particular across vertebrates with internal and external fertilization. Here we show that 33 genes among the 69 that have been experimentally shown to be involved in fertilization in at least one taxon in vertebrates are under positive selection. Moreover, we identified 17 pseudogenes and 39 genes that have at least one duplicate in one species. For 15 genes, we found neither positive selection, nor gene copies or pseudogenes. Genes of teleosts, especially genes involved in sperm-oolemma fusion, appear to be more frequently under positive selection than genes of birds and eutherians. In contrast, pseudogenization, gene loss and gene gain are more frequent in eutherians. Thus, each of the 19 studied vertebrate species exhibits a unique signature characterized by gene gain and loss, as well as position of amino acids under positive selection. Reflecting these clade-specific signatures, teleosts and eutherian mammals are recovered as clades in a parsimony analysis. Interestingly the same analysis places Xenopus apart from teleosts, with which it shares the primitive external fertilization, and locates it along with amniotes (which share internal fertilization), suggesting that external or internal environmental conditions of germ cell interaction may not be the unique factors that drive the evolution of fertilization genes. Our work should improve our understanding of the fertilization process and on the establishment of reproductive barriers, for example by offering new leads for experiments on genes identified as positively selected. PMID:22957080

  7. Decision-Making Guide for the Proposed Coast Guard Differential Global Positioning System

    DTIC Science & Technology

    1991-06-01

    DIFFERENTIAL GLOBAL POSITIONING SYSTEM by Robert J. Wilson June, 1991 Thesis Co-Advisors: Dan C. Boger Kurt Schnebele Approved for public release; distribution...Wilson Approved by: -Dan C. Boger, Thesis Co dvisor Kurt Scnebele, CaIn, NOAA, Thesis Co-Advisor -4v David R. Whipple, Chairman Department of...Group, 9 April 1990, Coast Guard Research and Development Center, Groton, CT. 20. Kremer , G.T., and others, ’The Effect of Selective Availability on

  8. The use of an in situ portable flume to examine the effect of flow properties on the capture probability of juvenile Atlantic salmon

    NASA Astrophysics Data System (ADS)

    Roy, M. L.; Roy, A. G.; Grant, J. W.

    2013-12-01

    For stream fish, flow properties have been shown to influence energy expenses and habitat selection. Furthermore, flow properties directly influence the velocity of drifting prey items, therefore influencing the probability of fish at catch prey. Flow properties might also have an effect on prey trajectories that can become more unpredictable with increased turbulence. In this study, we combined field and experimental approaches to examine the foraging behaviour and position choice of juvenile Atlantic salmon in various flow conditions. We used an in situ portable flume, which consists in a transparent enclosure (observation section) equipped with hinged doors upstream allowing to funnel the water inside and modify flow properties. Portable flumes have been developed and used to simulate benthic invertebrate drift and sediment transport, but have not been previously been used to examine fish behaviour. Specifically, we tested the predictions that 1) capture probability declined with turbulence, 2) the number of attacks and the proportion of time spent on the substrate decreased with turbulence and 3) parr will preferably selected focal positions with lower turbulence than random locations across the observation section. The portable flume allowed creating four flow treatments on a gradient of mean downstream velocity and turbulence. Fish were fed with brine shrimps and filmed through translucent panels using a submerged camera. Twenty-three juvenile salmon were captured and submitted to each flow treatment for 20 minutes feeding trials. Our results showed high inter-individual variability in the foraging success and time budget within each flow treatment associated to levels of velocity and turbulence. However, the average prey capture probability for the two lower velocity treatments was higher than that for the two higher velocity treatments. An inverse relationship between flow velocity and prey capture probability was observed and might have resulted from a diminution in prey detection distance. Fish preferentially selected focal positions in moderate velocity, and low turbulence areas and avoided the highly turbulent locations. Similarly, selection of average downward velocity and avoidance of upward velocity might be associated to the ease at maintaining position. Considering the streamlined shape providing high hydrodynamism, average vertical velocity might be an important feature driving microhabitat selection. Our results do not rule out the effect of turbulence on fish foraging but rather highlights the need to further investigate this question with a wider range of hydraulic values in order to possibly implement a turbulence-dependent prey capture function that might be useful to mechanistic foraging models.

  9. Research & market strategy: how choice of drug discovery approach can affect market position.

    PubMed

    Sams-Dodd, Frank

    2007-04-01

    In principal, drug discovery approaches can be grouped into target- and function-based, with the respective aims of developing either a target-selective drug or a drug that produces a specific biological effect irrespective of its mode of action. Most analyses of drug discovery approaches focus on productivity, whereas the strategic implications of the choice of drug discovery approach on market position and ability to maintain market exclusivity are rarely considered. However, a comparison of approaches from the perspective of market position indicates that the functional approach is superior for the development of novel, innovative treatments.

  10. [Effect of tigecycline on selected multiresistant bacteria].

    PubMed

    Kolár, Milan; Hanulík, Vojtech; Chromá, Magdalena

    2009-02-01

    Currently, one of the most serious problems in medicine is the increasing resistance of pathogenic bacteria to antimicrobial drugs. Bacterial resistance may potentially be solved in particular by decreasing the consumption of antibiotics and increasing the quality of their use. Equally important, however, is the development of new antimicrobial drugs and their use in clinical practice. One of the new antibiotic agents is tigecycline of the glycylcycline group. The presented work aimed at assessing its in vitro effect on selected multiresistant bacteria. Clinical samples were collected from patients hospitalized in the University Hospital Olomouc to isolate ESBL- and AmpC beta-lactamase-producing enterobacteria, methicillin-resistant Staphylococcus aureus (MRSA) strains and vancomycin-resistant enterococci (VRE). In the isolates, susceptibility to tigecycline was determined by the standard microdilution method. A total of 350 isolates were tested (100 MRSA, 10 0 VRE, 100 ESBL-positive and 50 AmpC-positive enterobacteria). In the cases of VRE and MRSA, no resistance to tigecycline was detected and the minimum inhibitory concentrations (MIC) did not exceed 0.25 mg/l and 0.5 mg/l, respectively. In ESBL-positive enterobacteria, 97% susceptibility (MIC range = or <0.06 to 4 mg/l) was detected; in AmpC-positive enterobacteria, the MIC range was = or <0.03-2 mg/l and susceptibility reached 98 %. Tigecycline may be considered a suitable alternative in the treatment of infections caused by the above-mentioned multiresistant strains.

  11. 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.

  12. 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

  13. Selective biosensing of Staphylococcus aureus using chitosan quantum dots

    NASA Astrophysics Data System (ADS)

    Abdelhamid, Hani Nasser; Wu, Hui-Fen

    2018-01-01

    Selective biosensing of Staphylococcus aureus (S. aureus) using chitosan modified quantum dots (CTS@CdS QDs) in the presence of hydrogen peroxide is reported. The method is based on the intrinsic positive catalase activity of S. aureus. CTS@CdS quantum dots provide high dispersion in aqueous media with high fluorescence emission. Staphylococcus aureus causes a selective quenching of the fluorescence emission of CTS@CdS QDs in the presence of H2O2 compared to other pathogens such as Escherichia coli and Pseudomonas aeruginosa. The intrinsic enzymatic character of S. aureus (catalase positive) offers selective and fast biosensing. The present method is highly selective for positive catalase species and requires no expensive reagents such as antibodies, aptamers or microbeads. It could be extended for other species that are positive catalase.

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

    PubMed

    Singh, Niraj K; Tyagi, Anuj

    2017-07-01

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

  15. 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.

  16. Characterising private and shared signatures of positive selection in 37 Asian populations.

    PubMed

    Liu, Xuanyao; Lu, Dongsheng; Saw, Woei-Yuh; Shaw, Philip J; Wangkumhang, Pongsakorn; Ngamphiw, Chumpol; Fucharoen, Suthat; Lert-Itthiporn, Worachart; Chin-Inmanu, Kwanrutai; Chau, Tran Nguyen Bich; Anders, Katie; Kasturiratne, Anuradhani; de Silva, H Janaka; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Takeuchi, Fumihiko; Yamamoto, Ken; Yokota, Mitsuhiro; Mamatyusupu, Dolikun; Yang, Wenjun; Chung, Yeun-Jun; Jin, Li; Hoh, Boon-Peng; Wickremasinghe, Ananda R; Ong, RickTwee-Hee; Khor, Chiea-Chuen; Dunstan, Sarah J; Simmons, Cameron; Tongsima, Sissades; Suriyaphol, Prapat; Kato, Norihiro; Xu, Shuhua; Teo, Yik-Ying

    2017-04-01

    The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection. We performed population structure analyses of the ADP populations and divided these populations into four major groups based on their genographic information. By applying a highly sensitive algorithm haploPS to locate genomic signatures of positive selection, 140 distinct genomic regions exhibiting evidence of positive selection in at least one population were identified. We examined the extent of signal sharing for regions that were selected in multiple populations and observed that populations clustered in a similar fashion to that of how the ancestry clades were phylogenetically defined. In particular, populations predominantly located in South Asia underwent considerably different adaptation as compared with populations from the other geographical regions. Signatures of positive selection present in multiple geographical regions were predicted to be older and have emerged prior to the separation of the populations in the different regions. In contrast, selection signals present in a single population group tended to be of lower frequencies and thus can be attributed to recent evolutionary events.

  17. Characterising private and shared signatures of positive selection in 37 Asian populations

    PubMed Central

    Liu, Xuanyao; Lu, Dongsheng; Saw, Woei-Yuh; Shaw, Philip J; Wangkumhang, Pongsakorn; Ngamphiw, Chumpol; Fucharoen, Suthat; Lert-itthiporn, Worachart; Chin-inmanu, Kwanrutai; Chau, Tran Nguyen Bich; Anders, Katie; Kasturiratne, Anuradhani; de Silva, H Janaka; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Takeuchi, Fumihiko; Yamamoto, Ken; Yokota, Mitsuhiro; Mamatyusupu, Dolikun; Yang, Wenjun; Chung, Yeun-Jun; Jin, Li; Hoh, Boon-Peng; Wickremasinghe, Ananda R; Ong, RickTwee-Hee; Khor, Chiea-Chuen; Dunstan, Sarah J; Simmons, Cameron; Tongsima, Sissades; Suriyaphol, Prapat; Kato, Norihiro; Xu, Shuhua; Teo, Yik-Ying

    2017-01-01

    The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection. We performed population structure analyses of the ADP populations and divided these populations into four major groups based on their genographic information. By applying a highly sensitive algorithm haploPS to locate genomic signatures of positive selection, 140 distinct genomic regions exhibiting evidence of positive selection in at least one population were identified. We examined the extent of signal sharing for regions that were selected in multiple populations and observed that populations clustered in a similar fashion to that of how the ancestry clades were phylogenetically defined. In particular, populations predominantly located in South Asia underwent considerably different adaptation as compared with populations from the other geographical regions. Signatures of positive selection present in multiple geographical regions were predicted to be older and have emerged prior to the separation of the populations in the different regions. In contrast, selection signals present in a single population group tended to be of lower frequencies and thus can be attributed to recent evolutionary events. PMID:28098149

  18. ['Clinical auditing', a novel tool for quality assessment in surgical oncology].

    PubMed

    van Leersum, Nicoline J; Kolfschoten, Nikki E; Klinkenbijl, Jean H G; Tollenaar, Rob A E M; Wouters, Michel W J M

    2011-01-01

    To determine whether systematic audit and feedback of information about the process and outcomes improve the quality of surgical care. Systematic literature review. Embase, PubMed, and Web of Science databases were searched for publications on 'quality assessment' and 'surgery'. The references of the publications found were examined as well. Publications were included in the review if the effect of auditing on the quality of surgical care had been investigated. In the databases 2415 publications were found. After selection, 28 publications describing the effect of auditing, whether or not combined with a quality improvement project, on guideline adherence or indications of outcomes of care were included. In 21 studies, a statistically significant positive effect of auditing was reported. In 5 studies a positive effect was found, but this was either not significant or statistical significance was not determined. In 2 studies no effect was observed. 5 studies compared the combination of auditing with a quality improvement project with auditing alone; 4 of these reported an additional effect of the quality improvement project. Audit and feedback of quality information seem to have a positive effect on the quality of surgical care. The use of quality information from audits for the purpose of a quality improvement project can enhance the positive effect of the audit.

  19. Developmental Environment Effects on Sexual Selection in Male and Female Drosophila melanogaster

    PubMed Central

    Morimoto, Juliano; Pizzari, Tommaso; Wigby, Stuart

    2016-01-01

    The developmental environment can potentially alter the adult social environment and influence traits targeted by sexual selection such as body size. In this study, we manipulated larval density in male and female Drosophila melanogaster, which results in distinct adult size phenotypes–high (low) densities for small (large) adults–and measured sexual selection in experimental groups consisting of adult males and females from high, low, or a mixture of low and high larval densities. Overall, large adult females (those reared at low larval density) had more matings, more mates and produced more offspring than small females (those reared at high larval density). The number of offspring produced by females was positively associated with their number of mates (i.e. there was a positive female Bateman gradient) in social groups where female size was experimentally varied, likely due to the covariance between female productivity and mating rate. For males, we found evidence that the larval environment affected the relative importance of sexual selection via mate number (Bateman gradients), mate productivity, paternity share, and their covariances. Mate number and mate productivity were significantly reduced for small males in social environments where males were of mixed sizes, versus social environments where all males were small, suggesting that social heterogeneity altered selection on this subset of males. Males are commonly assumed to benefit from mating with large females, but in contrast to expectations we found that in groups where both the male and female size varied, males did not gain more offspring per mating with large females. Collectively, our results indicate sex-specific effects of the developmental environment on the operation of sexual selection, via both the phenotype of individuals, and the phenotype of their competitors and mates. PMID:27167120

  20. Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

    PubMed

    Lester, Kathryn J; Field, Andy P; Muris, Peter

    2011-01-01

    This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

  1. The partial-reinforcement extinction effect and the contingent-sampling hypothesis.

    PubMed

    Hochman, Guy; Erev, Ido

    2013-12-01

    The partial-reinforcement extinction effect (PREE) implies that learning under partial reinforcements is more robust than learning under full reinforcements. While the advantages of partial reinforcements have been well-documented in laboratory studies, field research has failed to support this prediction. In the present study, we aimed to clarify this pattern. Experiment 1 showed that partial reinforcements increase the tendency to select the promoted option during extinction; however, this effect is much smaller than the negative effect of partial reinforcements on the tendency to select the promoted option during the training phase. Experiment 2 demonstrated that the overall effect of partial reinforcements varies inversely with the attractiveness of the alternative to the promoted behavior: The overall effect is negative when the alternative is relatively attractive, and positive when the alternative is relatively unattractive. These results can be captured with a contingent-sampling model assuming that people select options that provided the best payoff in similar past experiences. The best fit was obtained under the assumption that similarity is defined by the sequence of the last four outcomes.

  2. 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

  3. Designing Superoxide-Generating Quantum Dots for Selective Light-Activated Nanotherapy

    NASA Astrophysics Data System (ADS)

    Goodman, Samuel M.; Levy, Max; Li, Fei-Fei; Ding, Yuchen; Courtney, Colleen M.; Chowdhury, Partha P.; Erbse, Annette; Chatterjee, Anushree; Nagpal, Prashant

    2018-03-01

    The rapid emergence of superbugs or multi-drug resistant (MDR) organisms has prompted a search for novel antibiotics, beyond traditional small-molecule therapies. Nanotherapeutics are being investigated as alternatives, and recently superoxide-generating quantum dots (QDs) have been shown as important candidates for selective light-activated therapy and potentiating existing antibiotics against MDR superbugs. Their therapeutic action is selective, can be tailored by simply changing their quantum-confined conduction-valence bands and their alignment with different redox half-reactions, and hence their ability to generate specific radical species in biological media. Here, we show the design of superoxide-generating QDs using optimal QD material and size well matched to superoxide redox potential, charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs with conduction band position at -0.5V with respect to Normal Hydrogen Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective superoxide radicals, thereby demonstrating the most effective light-activated therapy. Although the positively charged QDs demonstrate large cellular uptake, they bind indiscriminately to cell surfaces and cause non-selective cell death, while negatively charged and zwitterionic QD ligands reduce the uptake and allow selective therapeutic action via interaction with redox species. The stability of designed QDs in biologically-relevant media increases with the formation of core-shell QD structures, but an appropriate design of core-shell structures is needed to minimize any reduction in charge injection efficiency to adsorbed oxygen molecules (to form superoxide) and maintain similar quantitative generation of tailored redox species, as measured using electron paramagnetic resonance (EPR) spectroscopy and electrochemical impedance spectroscopy. Using these findings, we demonstrate the rational design of QDs as selective therapeutic kills more than 99% of priority class I pathogens, thus providing an effective therapy against MDR superbugs.

  4. Tuning transport selectivity of ionic species by phosphoric acid gradient in positively charged nanochannel membranes.

    PubMed

    Yang, Meng; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Fan, Xin; Liu, Wei; Liu, Xizhen; Liu, Jianbo; Huang, Jin

    2015-02-03

    The transport of ionic species through a nanochannel plays important roles in fundamental research and practical applications of the nanofluidic device. Here, we demonstrated that ionic transport selectivity of a positively charged nanochannel membrane can be tuned under a phosphoric acid gradient. When phosphoric acid solution and analyte solution were connected by the positively charged nanochannel membrane, the faster-moving analyte through the positively charged nanochannel membrane was the positively charged dye (methylviologen, MV(2+)) instead of the negatively charged dye (1,5-naphthalene disulfonate, NDS(2-)). In other words, a reversed ion selectivity of the nanochannel membranes can be found. It can be explained as a result of the combination of diffusion, induced electroosmosis, and induced electrophoresis. In addition, the influencing factors of transport selectivity, including concentration of phosphoric acid, penetration time, and volume of feed solution, were also investigated. The results showed that the transport selectivity can further be tuned by adjusting these factors. As a method of tuning ionic transport selectivity by establishing phosphoric acid gradient, it will be conducive to improving the separation of ionic species.

  5. Amido-Schiff base derivatives as colorimetric fluoride sensor: Effect of nitro substitution on the sensitivity and color change.

    PubMed

    Ghosh, Soumen; Alam, Md Akhtarul; Ganguly, Aniruddha; Guchhait, Nikhil

    2015-01-01

    A series of Schiff bases synthesized by the condensation of benzohydrazide and -NO2 substituted benzaldehyde have been used as selective fluoride ion sensor. Test paper coated with these synthetic Schiff bases (test kits) can detect fluoride ion selectively with a drastic color change and detection can be achieved by just using the naked-eye without the help of any optical instrument. Interestingly, the position of -NO2 group in the amido Schiff bases has an effect on the sensitivity as well as on the change of color of species. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Effect of damping on excitability of high-order normal modes. [for a large space telescope spacecraft

    NASA Technical Reports Server (NTRS)

    Merchant, D. H.; Gates, R. M.; Straayer, J. W.

    1975-01-01

    The effect of localized structural damping on the excitability of higher-order large space telescope spacecraft modes is investigated. A preprocessor computer program is developed to incorporate Voigt structural joint damping models in a finite-element dynamic model. A postprocessor computer program is developed to select critical modes for low-frequency attitude control problems and for higher-frequency fine-stabilization problems. The selection is accomplished by ranking the flexible modes based on coefficients for rate gyro, position gyro, and optical sensor, and on image-plane motions due to sinusoidal or random PSD force and torque inputs.

  7. Positive messages enhance older adults' motivation and recognition memory for physical activity programmes.

    PubMed

    Notthoff, Nanna; Klomp, Peter; Doerwald, Friederike; Scheibe, Susanne

    2016-09-01

    Although physical activity is an effective way to cope with ageing-related impairments, few older people are motivated to turn their sedentary lifestyle into an active one. Recent evidence suggests that walking can be more effectively promoted in older adults with positive messages about the benefits of walking than with negative messages about the risks of inactivity. This study examined motivation and memory as the supposed mechanisms underlying the greater effectiveness of positively framed compared to negatively framed messages for promoting activity. Older adults ( N  = 53, age 60-87 years) were introduced to six physical activity programmes that were randomly paired with either positively framed or negatively framed messages. Participants indicated how motivated they were to participate in each programme by providing ratings on attractiveness, suitability, capability and intention. They also completed surprise free recall and recognition tests. Respondents felt more motivated to participate in physical activity programmes paired with positively framed messages than in those with negatively framed ones. They also had better recognition memory for positively framed than negatively framed messages, and misremembered negatively framed messages to be positively framed. Findings support the notion that socioemotional selectivity theory-a theory of age-related changes in motivation-is a useful basis for health intervention design.

  8. Music-induced positive mood broadens the scope of auditory attention.

    PubMed

    Putkinen, Vesa; Makkonen, Tommi; Eerola, Tuomas

    2017-07-01

    Previous studies indicate that positive mood broadens the scope of visual attention, which can manifest as heightened distractibility. We used event-related potentials (ERP) to investigate whether music-induced positive mood has comparable effects on selective attention in the auditory domain. Subjects listened to experimenter-selected happy, neutral or sad instrumental music and afterwards participated in a dichotic listening task. Distractor sounds in the unattended channel elicited responses related to early sound encoding (N1/MMN) and bottom-up attention capture (P3a) while target sounds in the attended channel elicited a response related to top-down-controlled processing of task-relevant stimuli (P3b). For the subjects in a happy mood, the N1/MMN responses to the distractor sounds were enlarged while the P3b elicited by the target sounds was diminished. Behaviorally, these subjects tended to show heightened error rates on target trials following the distractor sounds. Thus, the ERP and behavioral results indicate that the subjects in a happy mood allocated their attentional resources more diffusely across the attended and the to-be-ignored channels. Therefore, the current study extends previous research on the effects of mood on visual attention and indicates that even unfamiliar instrumental music can broaden the scope of auditory attention via its effects on mood. © The Author (2017). Published by Oxford University Press.

  9. Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV Protease Inhibitor Nelfinavir

    PubMed Central

    2012-01-01

    Background Human epidermal growth factor receptor 2 (HER2)–positive breast cancer is highly aggressive and has higher risk of recurrence than HER2-negative cancer. With few treatment options available, new drug targets specific for HER2-positive breast cancer are needed. Methods We conducted a pharmacological profiling of seven genotypically distinct breast cancer cell lines using a subset of inhibitors of breast cancer cells from a screen of the Johns Hopkins Drug Library. To identify molecular targets of nelfinavir, identified in the screen as a selective inhibitor of HER2-positive cells, we conducted a genome-wide screen of a haploinsufficiency yeast mutant collection. We evaluated antitumor activity of nelfinavir with xenografts in athymic nude mouse models (n = 4–6 per group) of human breast cancer and repeated mixed-effects regression analysis. All statistical tests were two-sided. Results Pharmacological profiling showed that nelfinavir, an anti-HIV drug, selectively inhibited the growth of HER2-positive breast cancer cells in vitro. A genome-wide screening of haploinsufficiency yeast mutants revealed that nelfinavir inhibited heat shock protein 90 (HSP90) function. Further characterization using proteolytic footprinting experiments indicated that nelfinavir inhibited HSP90 in breast cancer cells through a novel mechanism. In vivo, nelfinavir selectively inhibited the growth of HER2-positive breast cancer cells (tumor volume index of HCC1954 cells on day 29, vehicle vs nelfinavir, mean = 14.42 vs 5.16, difference = 9.25, 95% confidence interval [CI] = 5.93 to 12.56, P < .001; tumor volume index of BT474 cells on day 26, vehicle vs nelfinavir, mean = 2.21 vs 0.90, difference = 1.31, 95% CI = 0.83 to 1.78, P < .001). Moreover, nelfinavir inhibited the growth of trastuzumab- and/or lapatinib-resistant, HER2-positive breast cancer cells in vitro at clinically achievable concentrations. Conclusion Nelfinavir was found to be a new class of HSP90 inhibitor and can be brought to HER2-breast cancer treatment trials with the same dosage regimen as that used among HIV patients. PMID:23042933

  10. Proceedings: Second User’s Workshop on Combat Stress Held at Fort Sam Houston, Texas on 29-30 April 1982.

    DTIC Science & Technology

    1983-12-01

    participant spaces are limited, selection for attendance will be based upon the following priorities: a. Unit is willing to have both line officers with...Proximity Re-Emerged as Primary Treatment Principle. * Clinical Picture: Tremors, Paralvsis, Mutism , Ganser Syndrome. 5. WW II: * lo Effective Treatment...aspects of the job, not on the danger. A soldier who is concentrating on firing his weacon and on selecting his next firing position is not concentrating

  11. A strategy for position-selective epoxidation of polyprenols.

    PubMed

    Gnanadesikan, Vijay; Corey, E J

    2008-06-25

    An effective strategy has been developed for the efficient site-selective epoxidation of poylolefinic isoprenoid alcohols, based on the use of an internal control element for intramolecular reaction. The approach is illustrated by application to a series of polyisoprenoid alcohols (polyprenols) at substrate concentration of 0.5 mM. With polyprenol substrates having the hydroxyl function at one terminus, the internal epoxidation can be directed at the double bond of the polyprenol, which is either four or five away from the terminal hydroxyprenyl subunit.

  12. Acurex Parabolic Dish Concentrator (PDC-2)

    NASA Technical Reports Server (NTRS)

    Overly, P.; Bedard, R.

    1982-01-01

    The design approach, rationale for the selected configuration, and the development status of a cost effective point-focus solar concentrator are discussed. The low-cost concentrator reflective surface design is based on the use of a thin, backsilvered mirror glass reflector bonded to a molded structural plastic substrate. The foundation, support, and drive subassembles are described. A hybrid, two-axis, Sun tracking control system based on microprocessor technology was selected. Coarse synthetic tracking is achieved through a microcomputer-based control system to calculate Sun position for transient periods of cloud cover as well as sundown and sunrise positioning. Accurate active tracking is achieved by two-axis optical sensors. Results of the reflective panel demonstration tests investigating slope error, hail impact survivability, temperature/humidity cycling, longitudinal strength/bending stiffness, and torsional stiffness are discussed.

  13. [Emotional processing in patients with a dissocial personality disorder subtype "psychopathy" according to PCL-R].

    PubMed

    Weber, Tatjana; Sommer, Monika; Hajak, Göran; Müller, Jürgen

    2004-11-01

    Functional MRI was used to test the effects of the deficient emotional responsiveness of psychopathic patients on cognitive processes. We used a Simon-paradigm, in which ten healthy volunteers and ten patients with a diagnosis of "psychopathy" (defined by Hare Psychopathy Checklist Revised) have to select their spatially defined responses on the basis of a nonspatial stimuli feature. For the emotion induction pictures from the International Affective Picture System (IAPS) were selected. At the beginning and intermediated by the Simon-paradigm blocks of positive, negative or neutral pictures were presented. Patients with "psychopathy" exhibited untypical activation patterns in amygdala and prefrontal regions during interferences between negative or positive stimulations and cognitive tasks. These results demonstrated disturbed regulation of emotion-cognition-interaction in "psychopathy" according to PCL-R.

  14. Ginseng-Aconite Decoction elicits a positive inotropic effect via the reverse mode Na+/Ca2+ exchanger in beating rabbit atria.

    PubMed

    Cui, Hao Zhen; Kim, Hye Yoom; Kang, Dae Gill; Lee, Ho Sub

    2013-07-09

    Ginseng-Aconite Decoction (GAD), a traditional oriental medicine composed of Panax ginseng C.A. Mey. (Araliaceae) and Aconitum carmichaeli Debx. (Ranunculaceae) has been used as treatment for cardiovascular diseases from Song Dynasty of China. The purpose of the present study was to elucidate the possible mechanisms of GAD-induced positive inotropic effect. GAD-induced changes in atrial dynamics and cAMP efflux were determined in isolated perfused beating rabbit atria. GAD significantly increased atrial dynamics such as stroke volume, pulse pressure and augmented cAMP efflux in beating rabbit atria. The inotropic effect was significantly attenuated by pre-treatment with KB-R7943, a reverse mode Na(+)/Ca(2+) exchanger blocker. The GAD-induced increase in atrial dynamics was also markedly inhibited by staurosporine, a non-selective protein kinase inhibitor, and partly blocked by KT5720, a selective PKA inhibitor. The effect of GAD on atrial dynamics was not altered by pre-treatment with propranolol, a β-adrenergic receptor inhibitor, or diltiazem, an L-type Ca(2+)channel blocker. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) failed to modulate the GAD-induced increase in atrial dynamics, but markedly attenuated cAMP efflux in the beating atria. These results suggest that the GAD-induced positive inotropic effect in beating rabbit atria may be attributable to stimulation of the reverse mode Na(+)/Ca(2+) exchanger, while PKA activity would, at least in part, be participated in the course. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Speech perception in older listeners with normal hearing:conditions of time alteration, selective word stress, and length of sentences.

    PubMed

    Cho, Soojin; Yu, Jyaehyoung; Chun, Hyungi; Seo, Hyekyung; Han, Woojae

    2014-04-01

    Deficits of the aging auditory system negatively affect older listeners in terms of speech communication, resulting in limitations to their social lives. To improve their perceptual skills, the goal of this study was to investigate the effects of time alteration, selective word stress, and varying sentence lengths on the speech perception of older listeners. Seventeen older people with normal hearing were tested for seven conditions of different time-altered sentences (i.e., ±60%, ±40%, ±20%, 0%), two conditions of selective word stress (i.e., no-stress and stress), and three different lengths of sentences (i.e., short, medium, and long) at the most comfortable level for individuals in quiet circumstances. As time compression increased, sentence perception scores decreased statistically. Compared to a natural (or no stress) condition, the selectively stressed words significantly improved the perceptual scores of these older listeners. Long sentences yielded the worst scores under all time-altered conditions. Interestingly, there was a noticeable positive effect for the selective word stress at the 20% time compression. This pattern of results suggests that a combination of time compression and selective word stress is more effective for understanding speech in older listeners than using the time-expanded condition only.

  16. Design, Synthesis and Biological Evaluation of Histone Deacetylase (HDAC) Inhibitors: Saha (Vorinostat) Analogs and Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity

    NASA Astrophysics Data System (ADS)

    Negmeldin, Ahmed Thabet

    HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools to help understand the HDAC-related cancer biology. Our strategy was based on synthesis and screening of several derivatives of the non-selective FDA approved drug SAHA substituted at different positions of the linker region. Several SAHA analogs modified at the C4 and C5 positions of the linker were synthesized. The new C4- and C5-modified SAHA libraries, along with the previously synthesized C2-modified SAHA analogs were screened in vitro and in cellulo for HDAC isoform selectivity. Interestingly, several analogs exhibited dual HDAC6/HDAC8 selectivity. Enantioselective syntheses of the pure enantiomers of some of the interesting analogs were performed and the enantiomers were screened in vitro. Among the most interesting analogs, ( R)-C4-benzyl SAHA displayed 520- to 1300-fold selectivity for HDAC6 and HDAC8 over HDAC1, 2, and 3, with IC50 values of 48 and 27 nM with HDAC6 and 8, respectively. Docking studies were performed to provide structural rationale for the observed selectivity of the new analogs. In addition, rational design, synthesis, and screening of several other biaryl indolyl benzamide HDAC inhibitors is discussed, and some showed modest HDAC1 selectivity. The new biaryl indolyl benzamides can be useful to further develop HDAC1 selective inhibitors. The dual HDAC6/8 selective inhibitors can be used as lead compounds and as a chemical tool to study HDAC related cancer biology. The observed enhancement of selectivity upon modifying the linker region of the non-selective inhibitor SAHA shows that modifying current drugs, like SAHA, could lead to substantial improvement in its pharmacodynamic properties.

  17. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

  18. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

  19. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

  20. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

  1. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

  2. GWASinlps: Nonlocal prior based iterative SNP selection tool for genome-wide association studies.

    PubMed

    Sanyal, Nilotpal; Lo, Min-Tzu; Kauppi, Karolina; Djurovic, Srdjan; Andreassen, Ole A; Johnson, Valen E; Chen, Chi-Hua

    2018-06-19

    Multiple marker analysis of the genome-wide association study (GWAS) data has gained ample attention in recent years. However, because of the ultra high-dimensionality of GWAS data, such analysis is challenging. Frequently used penalized regression methods often lead to large number of false positives, whereas Bayesian methods are computationally very expensive. Motivated to ameliorate these issues simultaneously, we consider the novel approach of using nonlocal priors in an iterative variable selection framework. We develop a variable selection method, named, iterative nonlocal prior based selection for GWAS, or GWASinlps, that combines, in an iterative variable selection framework, the computational efficiency of the screen-and-select approach based on some association learning and the parsimonious uncertainty quantification provided by the use of nonlocal priors. The hallmark of our method is the introduction of 'structured screen-and-select' strategy, that considers hierarchical screening, which is not only based on response-predictor associations, but also based on response-response associations, and concatenates variable selection within that hierarchy. Extensive simulation studies with SNPs having realistic linkage disequilibrium structures demonstrate the advantages of our computationally efficient method compared to several frequentist and Bayesian variable selection methods, in terms of true positive rate, false discovery rate, mean squared error, and effect size estimation error. Further, we provide empirical power analysis useful for study design. Finally, a real GWAS data application was considered with human height as phenotype. An R-package for implementing the GWASinlps method is available at https://cran.r-project.org/web/packages/GWASinlps/index.html. Supplementary data are available at Bioinformatics online.

  3. Selective activation of group III metabotropic glutamate receptor subtypes produces different patterns of γ-aminobutyric acid immunoreactivity and glutamate release in the retina.

    PubMed

    Guimarães-Souza, E M; Calaza, K C

    2012-12-01

    Glutamate, the major excitatory neurotransmitter in the retina, functions by activation of both ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors. Group III mGluRs, except for mGluR6, are mostly found in the inner plexiform layer (IPL), and their retinal functions are not well known. Therefore, we decided to investigate the effect of mGluRIII on glutamate release and GABAergic amacrine cells in the chick retina. The nonselective mGluRIII agonist L-SOP promoted a decrease in the number of γ-aminobutyric acid (GABA)-positive cells and in the GABA immunoreactivity in all sublayers of the IPL. This effect was prevented by the antagonist MAP-4, by GAT-1 inhibitor, and by antagonists of iGluR. Under the conditions used, L-SOP did not alter endogenous glutamate release. VU0155041, an mGluR4-positive allosteric modulator, reduced GABA immunoreactivity in amacrine cells and in sublayers 2 and 4 of the IPL but evoked an increase in the glutamate released. VU0155041's effect was inhibited by the absence of calcium. AMN082, a selective mGluR7-positive allosteric modulator, also decreased GABA immunoreactivity in amacrine cells and sublayers 1, 2, and 3 and increased glutamate release, and this effect was also inhibited by calcium absence. DCPG, an mGluR8-selective agonist, did not significantly alter GABA immunoreactivity in amacrine cells or glutamate release. However, it did significantly increase GABA immunoreactivity in sublayers 4 and 5. The results suggest that mGluRIIIs are involved in the modulation of glutamate and GABA release in the retina, possibly participating in distinct visual pathways: mGluR4 might be involved with cholinergic circuitry, whereas mGluR7 and mGluR8 might participate, respectively, in the OFF and the ON pathways. Copyright © 2012 Wiley Periodicals, Inc.

  4. Mixed culture polyhydroxyalkanoates production from sugar molasses: the use of a 2-stage CSTR system for culture selection.

    PubMed

    Albuquerque, M G E; Concas, S; Bengtsson, S; Reis, M A M

    2010-09-01

    Polyhydroxyalkanoates (PHAs) are promising biodegradable polymers. The use of mixed microbial cultures (MMC) and low cost feedstocks have a positive impact on the cost-effectiveness of the process. It has typically been carried out in Sequencing Batch Reactors (SBR). In this study, a 2-stage CSTR system (under Feast and Famine conditions) was used to effectively select for PHA-storing organisms using fermented molasses as feedstock. The effect of influent substrate concentration (60-120 Cmmol VFA/L) and HRT ratio between the reactors (0.2-0.5h/h) on the system's selection efficiency was assessed. It was shown that Feast reactor residual substrate concentration impacted on the selective pressure for PHA storage (due to substrate-dependent kinetic limitation). Moreover, a residual substrate concentration coming from the Feast to the Famine reactor did not jeopardize the physiological adaptation required for enhanced PHA storage. The culture reached a maximum PHA content of 61%. This success opens new perspectives to the use of wastewater treatment infrastructure for PHA production, thus valorizing either excess sludge or wastewaters. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Evolutionary characterization of hemagglutinin gene of H9N2 influenza viruses isolated from Asia.

    PubMed

    Shahsavandi, Shahla; Salmanian, Ali-Hatef; Ghorashi, Seyed Ali; Masoudi, Shahin; Ebrahimi, Mohammad Majid

    2012-08-01

    The full length hemagglutinin (HA) genes of 287 H9N2 AI strains isolated from chickens in Asia during the period 1994-2009 were genetically analyzed. Phylogenetic analysis showed that G1-like viruses circulated in the Middle East and Indian sub-continent countries, whereas other sublineages existed in Far East countries. It also revealed G1-like viruses with an average 96.7% identity clustered into two subgroups largely based on their time of isolation. The Ka/Ks ratio was calculated 0.34 for subgroup 1 and 0.57 for subgroup 2 indicates purifying/stabilizing selection, but despite this there is evidence of localized positive selection when comparing the subgroups 1 and 2 protein sequences. Five sites in HA H9N2 viruses had a posterior probability >0.5 using the Bayesian method, indicating these sites were under positive selection. These sites were found to be associated with the globular head region of HA. To identify sites under positive selection; amino acid substitution classified depends on their radicalism and neutrality. The results indicate that, although most positions in HAs were under purifying selection and can be eliminated, a few positions located in the antigenic regions and receptor binding sites were subject to positive selection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Framing effects in medical situations: distinctions of attribute, goal and risky choice frames.

    PubMed

    Peng, Jiaxi; Jiang, Yuan; Miao, Danmin; Li, Rui; Xiao, Wei

    2013-06-01

    To verify whether three different framing effects (risky choice, attribute and goal) exist in simulated medical situations and to analyse any differences. Medical decision-making problems were established, relating to medical skill evaluation, patient compliance and a selection of treatment options. All problems were described in positive and negative frame conditions. Significantly more positive evaluations were made if the doctor's medical records were described as 'of 100 patients, 70 patients became better' compared with those described as 'of 100 patients, 30 patients didn't become better'. Doctor's advice described in a negative frame resulted in significantly more decisions to comply, compared with advice described in a positive frame. Treatment options described in terms of survival rates resulted in significantly more adventurous choices compared with options described in terms of mortality rates. Decision-making reversal appeared in the risky choice and attribute frames, but not the goal frame. Framing effects were shown to exist in simulated medical situations, but there were significant differences among the three kinds of such effects.

  7. Striving for quality use of medicines: how effective is Australia's ban on direct-to-consumer prescription medicine advertising?

    PubMed

    Brown, Sonja

    2009-02-01

    The potential for both positive and negative effects arising from direct-to-consumer advertising of prescription medicines challenges health policymakers to develop regulatory schemes which selectively capture the positive aspects of the practice. Australia has dealt with this quandary by banning the practice, while New Zealand and the United States permit it. However, in recent times pharmaceutical companies have been increasingly successful in introducing promotional materials into the Australian market. This article demonstrates that the Australian ban is consistent with striving for the major policy goal of quality use of medicines, thus providing the basis for arguing that solutions to strengthen the ban against the identified threats ought to be implemented. Quality use of medicines can be most effectively achieved via the combined effect of the strengthened ban and the mimicking of the limited positive aspects of direct-to-consumer advertising by government provision of non-promotional information to consumers.

  8. Fear of Negative Evaluation Biases Social Evaluation Inference: Evidence from a Probabilistic Learning Task

    PubMed Central

    Button, Katherine S.; Kounali, Daphne; Stapinski, Lexine; Rapee, Ronald M.; Lewis, Glyn; Munafò, Marcus R.

    2015-01-01

    Background Fear of negative evaluation (FNE) defines social anxiety yet the process of inferring social evaluation, and its potential role in maintaining social anxiety, is poorly understood. We developed an instrumental learning task to model social evaluation learning, predicting that FNE would specifically bias learning about the self but not others. Methods During six test blocks (3 self-referential, 3 other-referential), participants (n = 100) met six personas and selected a word from a positive/negative pair to finish their social evaluation sentences “I think [you are / George is]…”. Feedback contingencies corresponded to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5 and 0.2, respectively. Results As FNE increased participants selected fewer positive words (β = −0.4, 95% CI −0.7, −0.2, p = 0.001), which was strongest in the self-referential condition (FNE × condition 0.28, 95% CI 0.01, 0.54, p = 0.04), and the neutral and dislike rules (FNE × condition × rule, p = 0.07). At low FNE the proportion of positive words selected for self-neutral and self-disliked greatly exceeded the feedback contingency, indicating poor learning, which improved as FNE increased. Conclusions FNE is associated with differences in processing social-evaluative information specifically about the self. At low FNE this manifests as insensitivity to learning negative self-referential evaluation. High FNE individuals are equally sensitive to learning positive or negative evaluation, which although objectively more accurate, may have detrimental effects on mental health. PMID:25853835

  9. Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity

    PubMed Central

    Shabalina, Svetlana A.; Spiridonov, Nikolay A.; Kashina, Anna

    2013-01-01

    Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. PMID:23293005

  10. Heavy Metal Uptake by C. esculentus, S. alterniflora and Agronomic Plants from Contaminated Soils and Sediments.

    DTIC Science & Technology

    1982-02-28

    in March and potted in April. Seed sowing will ta..-e place in mid-May. The species sown will include a grass. wheat, lettuce and radish and C... effects varied. Soe started negativeLy, and became positive; others remained negative ( radish ), and others were positive aLl the time (wheat). ALL...agronomic plants selected were radish (Webb’s French Break- fast), lettuce (Paris White), wheat (spring), red fescue (Merlin) and ryegrass (S24). Each

  11. The Impact of School-Wide Positive Behavior Support on Number of Office Discipline Referrals and the Financial Impact on the Allocation of Funds in Both High and Low Socioeconomic Status School Settings

    ERIC Educational Resources Information Center

    Kinsley, Sean Christopher

    2013-01-01

    The purpose of this study was to determine the effect of participation in School-Wide Positive Behavior Support on the number of office discipline referrals written and the financial impact it had on the allocation of funds in both high and low socioeconomic status schools in the selected school district. The top 10 percent of elementary schools…

  12. Enhancement of hepatitis virus immunoassay outcome predictions in imbalanced routine pathology data by data balancing and feature selection before the application of support vector machines.

    PubMed

    Richardson, Alice M; Lidbury, Brett A

    2017-08-14

    Data mining techniques such as support vector machines (SVMs) have been successfully used to predict outcomes for complex problems, including for human health. Much health data is imbalanced, with many more controls than positive cases. The impact of three balancing methods and one feature selection method is explored, to assess the ability of SVMs to classify imbalanced diagnostic pathology data associated with the laboratory diagnosis of hepatitis B (HBV) and hepatitis C (HCV) infections. Random forests (RFs) for predictor variable selection, and data reshaping to overcome a large imbalance of negative to positive test results in relation to HBV and HCV immunoassay results, are examined. The methodology is illustrated using data from ACT Pathology (Canberra, Australia), consisting of laboratory test records from 18,625 individuals who underwent hepatitis virus testing over the decade from 1997 to 2007. Overall, the prediction of HCV test results by immunoassay was more accurate than for HBV immunoassay results associated with identical routine pathology predictor variable data. HBV and HCV negative results were vastly in excess of positive results, so three approaches to handling the negative/positive data imbalance were compared. Generating datasets by the Synthetic Minority Oversampling Technique (SMOTE) resulted in significantly more accurate prediction than single downsizing or multiple downsizing (MDS) of the dataset. For downsized data sets, applying a RF for predictor variable selection had a small effect on the performance, which varied depending on the virus. For SMOTE, a RF had a negative effect on performance. An analysis of variance of the performance across settings supports these findings. Finally, age and assay results for alanine aminotransferase (ALT), sodium for HBV and urea for HCV were found to have a significant impact upon laboratory diagnosis of HBV or HCV infection using an optimised SVM model. Laboratories looking to include machine learning via SVM as part of their decision support need to be aware that the balancing method, predictor variable selection and the virus type interact to affect the laboratory diagnosis of hepatitis virus infection with routine pathology laboratory variables in different ways depending on which combination is being studied. This awareness should lead to careful use of existing machine learning methods, thus improving the quality of laboratory diagnosis.

  13. Effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation.

    PubMed

    Masuda, Yoshiki; Tatsumi, Hiroomi; Imaizumi, Hitoshi; Gotoh, Kyoko; Yoshida, Shinichiro; Chihara, Shinya; Takahashi, Kanako; Yamakage, Michiaki

    2014-03-01

    Prone ventilation is an effective method for improving oxygenation in patients with acute respiratory failure. However, in extracorporeal circulation, there is a risk of cannula-related complications when changing the position. In this study, we investigated cannula-related complications when changing position for prone ventilation and the effect of prone ventilation on impaired oxygenation in patients who underwent extracorporeal membrane oxygenation (ECMO). The study subjects were patients who underwent prone ventilation during ECMO in the period from 2004 to 2011. Indication for prone ventilation was the presence of dorsal infiltration shown by lung computed tomography. Factors investigated were cannula insertion site, dislodgement or obstruction of the cannula, malfunction of vascular access and unplanned dislodgement of the catheters when changing position. Mean arterial pressure, PaO2/FiO2, PEEP level, blood flow and rotation speed of the pump were also determined before and after position change. Five patients were selected as study subjects. The mean duration of prone positioning was 15.3 ± 0.5 h. Strict management during position changes prevented cannula-related complications in the patients who underwent extracorporeal circulation. There were no significant changes in mean arterial pressure, PEEP level, blood flow and rotation speed of the pump when changing position. Low PaO2/FiO2 prior to prone ventilation was significantly increased after supine to prone and then prone to supine position. Prone positioning to improve impaired oxygenation is a safe procedure and not a contraindication in patients receiving extracorporeal circulation.

  14. Relaxation of selection, niche construction, and the Baldwin effect in language evolution.

    PubMed

    Yamauchi, Hajime; Hashimoto, Takashi

    2010-01-01

    Deacon has suggested that one of the key factors of language evolution is not characterized by an increase in genetic contribution, often known as the Baldwin effect, but rather by a decrease. This process effectively increases linguistic learning capability by organizing a novel synergy of multiple lower-order functions previously irrelevant to the process of language acquisition. Deacon posits that this transition is not caused by natural selection. Rather, it is due to the relaxation of natural selection. While there are some cases in which relaxation caused by some external factors indeed induces the transition, we do not know what kind of relaxation has worked in language evolution. In this article, a genetic-algorithm-based computer simulation is used to investigate how the niche-constructing aspect of linguistic behavior may trigger the degradation of genetic predisposition related to language learning. The results show that agents initially increase their genetic predisposition for language learning—the Baldwin effect. They create a highly uniform sociolinguistic environment—a linguistic niche construction. This means that later generations constantly receive very similar inputs from adult agents, and subsequently the selective pressure to retain the genetic predisposition is relaxed.

  15. Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

    PubMed Central

    Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

    2015-01-01

    Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

  16. Positive responses to televised beer advertisements associated with drinking and problems reported by 18 to 29-year-olds.

    PubMed

    Wyllie, A; Zhang, J F; Casswell, S

    1998-05-01

    To examine the nature of the relationships between responses to alcohol advertisements and drinking behaviour and related problems. To examine the role of positive and negative beliefs about drinking as intervening variables. Survey utilizing a CATI (computer-assisted telephone interviewing) system, involving interviews with 1012 randomly selected respondents. Respondents were randomly selected from throughout New Zealand. Eighteen to twenty-nine-year-old New Zealanders. Response to specific alcohol advertisements was measured by recalled exposure (how often they recalled having seen the advertisements) and liking (a measure of positive response). An exploratory non-recursive structural equation model, based on 791 drinkers provided tentative support for the hypothesis that positive responses to televised beer advertisements (as measured by liking) contributed to the quantity of alcohol consumed on drinking occasions, which in turn contributed to the level of alcohol-related problems. The model, which provided a good fit to the data, was consistent with the hypothesis that liking of beer advertisements had both a direct influence on quantities of alcohol consumed and an indirect influence, via its influence on positive beliefs. These effects were present after controlling for reciprocal effects, none of which were significant. The data did not support the hypothesis that the quantities of alcohol consumed would influence the respondent's liking of beer advertisements. Recalled exposure was not a significant influence on the quantities consumed. The results are consistent with a number of theoretical perspectives and with a growing body of research that are suggestive of alcohol advertising having some influence on the consumption of younger people.

  17. Selective effects of acute alcohol intake on the prospective and retrospective components of a prospective-memory task with emotional targets.

    PubMed

    Walter, Nora T; Bayen, Ute J

    2016-01-01

    Prospective memory involves remembering to do something in the future and has a prospective component (remembering that something must be done) and a retrospective component (remembering what must be done and when it must be done). Initial studies reported an impairment in prospective-memory performance due to acute alcohol consumption. Retrospective-memory studies demonstrated that alcohol effects vary depending on the emotionality of the information that needs to be learned. The aim of the present study was to investigate possible differential effects of a mild acute alcohol dose (0.4 g/kg) on the prospective and retrospective components of prospective memory depending on cue valence. Seventy-five participants were allocated to an alcohol or placebo group and performed a prospective-memory task in which prospective-memory cue valence was manipulated (negative, neutral, positive). The multinomial model of event-based prospective memory (Smith and Bayen 2004) was used to measure alcohol and valence effects on the two prospective-memory components separately. Overall, no main effect of alcohol or valence on prospective-memory performance occurred. However, model-based analyses demonstrated a significantly higher retrospective component for positive compared with negative cues in the placebo group. In the alcohol group, the prospective component was weaker for negative than for neutral cues and the retrospective component was stronger for positive than for neutral cues. Group comparisons showed that the alcohol group had a significantly lower prospective component for negative cues and a lower retrospective component for neutral cues. This is the first study to demonstrate selective alcohol effects on prospective-memory components depending on prospective-memory cue valence.

  18. Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

    PubMed

    Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

    2014-05-01

    The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

  19. Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans

    PubMed Central

    Moretti, S.; Davydov, I.I.; Excoffier, L.

    2017-01-01

    Abstract Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier “significant” genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution. PMID:28333345

  20. Associations among selective attention, memory bias, cognitive errors and symptoms of anxiety in youth.

    PubMed

    Watts, Sarah E; Weems, Carl F

    2006-12-01

    The purpose of this study was to examine the linkages among selective attention, memory bias, cognitive errors, and anxiety problems by testing a model of the interrelations among these cognitive variables and childhood anxiety disorder symptoms. A community sample of 81 youth (38 females and 43 males) aged 9-17 years and their parents completed measures of the child's anxiety disorder symptoms. Youth completed assessments measuring selective attention, memory bias, and cognitive errors. Results indicated that selective attention, memory bias, and cognitive errors were each correlated with childhood anxiety problems and provide support for a cognitive model of anxiety which posits that these three biases are associated with childhood anxiety problems. Only limited support for significant interrelations among selective attention, memory bias, and cognitive errors was found. Finally, results point towards an effective strategy for moving the assessment of selective attention to younger and community samples of youth.

  1. Molecular evolution of the enzymes involved in the sphingolipid metabolism of Leishmania: selection pressure in relation to functional divergence and conservation.

    PubMed

    Mandlik, Vineetha; Shinde, Sonali; Singh, Shailza

    2014-06-21

    Selection pressure governs the relative mutability and the conservedness of a protein across the protein family. Biomolecules (DNA, RNA and proteins) continuously evolve under the effect of evolutionary pressure that arises as a consequence of the host parasite interaction. IPCS (Inositol phosphorylceramide synthase), SPL (Sphingosine-1-P lyase) and SPT (Serine palmitoyl transferase) represent three important enzymes involved in the sphingolipid metabolism of Leishmania. These enzymes are responsible for maintaining the viability and infectivity of the parasite and have been classified as druggable targets in the parasite metabolome. The present work relates to the role of selection pressure deciding functional conservedness and divergence of the drug targets. IPCS and SPL protein families appear to diverge from the SPT family. The three protein families were largely under the influence of purifying selection and were moderately conserved baring two residues in the IPCS protein which were under the influence of positive selection. To further explore the selection pressure at the codon level, codon usage bias indices were calculated to analyze genes for their synonymous codon usage pattern. IPCS gene exhibited slightly lower codon bias as compared to SPL and SPT protein families. Evolutionary tracing of the proposed drug targets has been done with a viewpoint that the amino-acids lining the drug binding pocket should have a lower evolvability. Sites under positive selection (HIS20 and CYS30 of IPCS) should be avoided during devising strategies for inhibitor design.

  2. Understanding the link between sexual selection, sexual conflict and aging using crickets as a model.

    PubMed

    Archer, C Ruth; Hunt, John

    2015-11-01

    Aging evolved because the strength of natural selection declines over the lifetime of most organisms. Weak natural selection late in life allows the accumulation of deleterious mutations and may favor alleles that have positive effects on fitness early in life, but costly pleiotropic effects expressed later on. While this decline in natural selection is central to longstanding evolutionary explanations for aging, a role for sexual selection and sexual conflict in the evolution of lifespan and aging has only been identified recently. Testing how sexual selection and sexual conflict affect lifespan and aging is challenging as it requires quantifying male age-dependent reproductive success. This is difficult in the invertebrate model organisms traditionally used in aging research. Research using crickets (Orthoptera: Gryllidae), where reproductive investment can be easily measured in both sexes, has offered exciting and novel insights into how sexual selection and sexual conflict affect the evolution of aging, both in the laboratory and in the wild. Here we discuss how sexual selection and sexual conflict can be integrated alongside evolutionary and mechanistic theories of aging using crickets as a model. We then highlight the potential for research using crickets to further advance our understanding of lifespan and aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Ten Years of Experience with a Performance-Based Promotional Selection and Career Development System within State Government.

    ERIC Educational Resources Information Center

    Baugher, Dan; And Others

    1994-01-01

    The New York State Division of Budget uses a decentralized system to assess promotion candidates by comparing their training, experience, and recent performance to the proposed position. Managers and candidates find the system more effective than traditional written/oral exams. (SK)

  4. 75 FR 67589 - Recruitment, Selection, and Placement (General)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... contains regulatory documents #0;having general applicability and legal effect, most of which are keyed #0... agencies, at their discretion, to designate a different local commuting area for RPL eligibles when the agency will not have any competitive service positions remaining in the local commuting area. The agency...

  5. On Using Various Mathematics Instructions versus Traditional Instruction: An Action Research

    ERIC Educational Resources Information Center

    Alzabut, Jehad

    2017-01-01

    In this research, I provide an overview of potentially selected interactive mathematical instructions that help learners-educators identifying the most effective practices for teaching a course on differential equations. Based on my practical experience, positive and negative aspects of the used techniques are discussed. Immediate reactions on the…

  6. Effects of Systematic Human Relations Training on Inmate Participants

    ERIC Educational Resources Information Center

    Davis, E. Duane; And Others

    1976-01-01

    The present study was conducted to determine the applicability of human relations training in the rehabilitation of selected prisoners in a Southern prison. Inmates who participated in the study were able to learn discrimination between helpful and nonhelpful communication and to make positive gains in their work behavior. (Author)

  7. Dominant positive and negative selection using a hygromycin phosphotransferase-thymidine kinase fusion gene.

    PubMed

    Lupton, S D; Brunton, L L; Kalberg, V A; Overell, R W

    1991-06-01

    The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable phenotypes may be expressed and regulated as a single genetic entity.

  8. Effect of biofilm and selective mixed culture on microbial fuel cell for the treatment of tempeh industrial wastewater

    NASA Astrophysics Data System (ADS)

    Arbianti, Rita; Surya Utami, Tania; Leondo, Vifki; Elisabeth; Andyah Putri, Syafira; Hermansyah, Heri

    2018-03-01

    Microbial Fuel Cell (MFC) provides a new alternative in the treatment of organic waste. MFC produces 50-90% less sludge to be disposed than other methods. MFC technology can utilize existing microorganisms in the waste as a catalyst to generate electricity and simultaneously also serves as a wastewater treatment unit itself. Tempeh wastewater is one of the abundant industrial wastewater which can be processed using MFC. Research using the selective mixed culture is very likely to do due to the good result on COD removals by adding mixed culture. Microorganisms in tempeh wastewater consist of bacteria gram positive and gram negative. This study focused on the aspects of waste treatment which is determined by decreased levels of COD and BOD. Variations in this study are the formation time of biofilm and the addition of selective gram. MFC operated for 50 hours. For a variation of biofilm formation, experiments were performed after incubation by replacing incubation substrates used in the formation of biofilms. Biofilm formation time in this study was 3 days, 5 days, 7 days and 14 days. Gram positive and gram negative bacteria were used in selective mixed culture experiments. Selective mixed culture added to the reactor by 1 mL and 5 mL. Selection of gram-positive or gram-negative bacteria carried by growing mixed culture on selective media. COD and BOD levels were measured in the wastewater before and after the experiment conducted in each variation. Biofilm formation optimum time is 7 days which decrease COD and BOD levels by 18.2% and 35.9%. The addition of gram negative bacteria decreases COD and BOD levels by 29.32% and 51.32%. Further research is needed in order to get a better result on decreasing levels of COD and BOD.

  9. Sexual selection and allometry: a critical reappraisal of the evidence and ideas.

    PubMed

    Bonduriansky, Russell

    2007-04-01

    One of the most pervasive ideas in the sexual selection literature is the belief that sexually selected traits almost universally exhibit positive static allometries (i.e., within a sample of conspecific adults, larger individuals have disproportionally larger traits). In this review, I show that this idea is contradicted by empirical evidence and theory. Although positive allometry is a typical attribute of some sexual traits in certain groups, the preponderance of positively allometric sexual traits in the empirical literature apparently results from a sampling bias reflecting a fascination with unusually exaggerated (bizarre) traits. I review empirical examples from a broad range of taxa illustrating the diversity of allometric patterns exhibited by signal, weapon, clasping and genital traits, as well as nonsexual traits. This evidence suggests that positive allometry may be the exception rather than the rule in sexual traits, that directional sexual selection does not necessarily lead to the evolution of positive allometry and, conversely, that positive allometry is not necessarily a consequence of sexual selection, and that many sexual traits exhibit sex differences in allometric intercept rather than slope. Such diversity in the allometries of secondary sexual traits is to be expected, given that optimal allometry should reflect resource allocation trade-offs, and patterns of sexual and viability selection on both trait size and body size. An unbiased empirical assessment of the relation between sexual selection and allometry is an essential step towards an understanding of this diversity.

  10. Rapid Detection of Positive Selection in Genes and Genomes Through Variation Clusters

    PubMed Central

    Wagner, Andreas

    2007-01-01

    Positive selection in genes and genomes can point to the evolutionary basis for differences among species and among races within a species. The detection of positive selection can also help identify functionally important protein regions and thus guide protein engineering. Many existing tests for positive selection are excessively conservative, vulnerable to artifacts caused by demographic population history, or computationally very intensive. I here propose a simple and rapid test that is complementary to existing tests and that overcomes some of these problems. It relies on the null hypothesis that neutrally evolving DNA regions should show a Poisson distribution of nucleotide substitutions. The test detects significant deviations from this expectation in the form of variation clusters, highly localized groups of amino acid changes in a coding region. In applying this test to several thousand human–chimpanzee gene orthologs, I show that such variation clusters are not generally caused by relaxed selection. They occur in well-defined domains of a protein's tertiary structure and show a large excess of amino acid replacement over silent substitutions. I also identify multiple new human–chimpanzee orthologs subject to positive selection, among them genes that are involved in reproductive functions, immune defense, and the nervous system. PMID:17603100

  11. Functional divergence in nitrogen uptake rates explains diversity-productivity relationship in microalgal communities

    DOE PAGES

    Mandal, Shovon; Shurin, Jonathan B.; Efroymson, Rebecca A.; ...

    2018-05-23

    The relationship between biodiversity and productivity has emerged as a central theme in ecology. Mechanistic explanations for this relationship suggest that the role organisms play in the ecosystem (i.e., niches or functional traits) is a better predictor of ecosystem stability and productivity than taxonomic richness. Here, we tested the capacity of functional diversity in nitrogen uptake in experimental microalgal communities to predict the complementarity effect (CE) and selection effect (SE) of biodiversity on productivity. We grew five algal species as monocultures and as polycultures in pairwise combinations in homogeneous (ammonium, nitrate, or urea alone) and heterogeneous nitrogen (mixed nitrogen) environmentsmore » to determine whether complementarity between species may be enhanced in heterogeneous environments. We show that the positive diversity effects on productivity in heterogeneous environments resulted from complementarity effects with no positive contribution by species–specific SEs. Positive biodiversity effects in homogeneous environments, when present (nitrate and urea treatments but not ammonium), were driven both by CE and SE. Our results suggest that functional diversity increases species complementarity and productivity mainly in heterogeneous resource environments. Furthermore, these results provide evidence that the positive effect of functional diversity on community productivity depends on the diversity of resources present in the environment.« less

  12. Functional divergence in nitrogen uptake rates explains diversity-productivity relationship in microalgal communities

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

    Mandal, Shovon; Shurin, Jonathan B.; Efroymson, Rebecca A.

    The relationship between biodiversity and productivity has emerged as a central theme in ecology. Mechanistic explanations for this relationship suggest that the role organisms play in the ecosystem (i.e., niches or functional traits) is a better predictor of ecosystem stability and productivity than taxonomic richness. Here, we tested the capacity of functional diversity in nitrogen uptake in experimental microalgal communities to predict the complementarity effect (CE) and selection effect (SE) of biodiversity on productivity. We grew five algal species as monocultures and as polycultures in pairwise combinations in homogeneous (ammonium, nitrate, or urea alone) and heterogeneous nitrogen (mixed nitrogen) environmentsmore » to determine whether complementarity between species may be enhanced in heterogeneous environments. We show that the positive diversity effects on productivity in heterogeneous environments resulted from complementarity effects with no positive contribution by species–specific SEs. Positive biodiversity effects in homogeneous environments, when present (nitrate and urea treatments but not ammonium), were driven both by CE and SE. Our results suggest that functional diversity increases species complementarity and productivity mainly in heterogeneous resource environments. Furthermore, these results provide evidence that the positive effect of functional diversity on community productivity depends on the diversity of resources present in the environment.« less

  13. The variable genomic architecture of isolation between hybridizing species of house mice.

    PubMed

    Teeter, Katherine C; Thibodeau, Lisa M; Gompert, Zachariah; Buerkle, C Alex; Nachman, Michael W; Tucker, Priscilla K

    2010-02-01

    Studies of the genetics of hybrid zones can provide insight into the genomic architecture of species boundaries. By examining patterns of introgression of multiple loci across a hybrid zone, it may be possible to identify regions of the genome that have experienced selection. Here, we present a comparison of introgression in two replicate transects through the house mouse hybrid zone through central Europe, using data from 41 single nucleotide markers. Using both genomic and geographic clines, we found many differences in patterns of introgression between the two transects, as well as some similarities. We found that many loci may have experienced the effects of selection at linked sites, including selection against hybrid genotypes, as well as positive selection in the form of genotypes introgressed into a foreign genetic background. We also found many positive associations of conspecific alleles among unlinked markers, which could be caused by epistatic interactions. Different patterns of introgression in the two transects highlight the challenge of using hybrid zones to identify genes underlying isolation and raise the possibility that the genetic basis of isolation between these species may be dependent on the local population genetic make-up or the local ecological setting.

  14. Path Diversity Improved Opportunistic Routing for Underwater Sensor Networks

    PubMed Central

    Wang, Haiyan; He, Ke

    2018-01-01

    The packets carried along a pre-defined route in underwater sensor networks are very vulnerble. Node mobility or intermittent channel availability easily leads to unreachable routing. Opportunistic routing has been proven to be a promising paradigm to design routing protocols for underwater sensor networks. It takes advantage of the broadcast nature of the wireless medium to combat packet losses and selects potential paths on the fly. Finding an appropriate forwarding candidate set is a key issue in opportunistic routing. Many existing solutions ignore the impact of candidates location distribution on packet forwarding. In this paper, a path diversity improved candidate selection strategy is applied in opportunistic routing to improve packet forwarding efficiency. It not only maximizes the packet forwarding advancements but also takes the candidate’s location distribution into account. Based on this strategy, we propose two effective routing protocols: position improved candidates selection (PICS) and position random candidates selection (PRCS). PICS employs two-hop neighbor information to make routing decisions. PRCS only uses one-hop neighbor information. Simulation results show that both PICS and PRCS can significantly improve network performance when compared with the previous solutions, in terms of packet delivery ratio, average energy consumption and end-to-end delay. PMID:29690621

  15. Path Diversity Improved Opportunistic Routing for Underwater Sensor Networks.

    PubMed

    Bai, Weigang; Wang, Haiyan; He, Ke; Zhao, Ruiqin

    2018-04-23

    The packets carried along a pre-defined route in underwater sensor networks are very vulnerble. Node mobility or intermittent channel availability easily leads to unreachable routing. Opportunistic routing has been proven to be a promising paradigm to design routing protocols for underwater sensor networks. It takes advantage of the broadcast nature of the wireless medium to combat packet losses and selects potential paths on the fly. Finding an appropriate forwarding candidate set is a key issue in opportunistic routing. Many existing solutions ignore the impact of candidates location distribution on packet forwarding. In this paper, a path diversity improved candidate selection strategy is applied in opportunistic routing to improve packet forwarding efficiency. It not only maximizes the packet forwarding advancements but also takes the candidate’s location distribution into account. Based on this strategy, we propose two effective routing protocols: position improved candidates selection (PICS) and position random candidates selection (PRCS). PICS employs two-hop neighbor information to make routing decisions. PRCS only uses one-hop neighbor information. Simulation results show that both PICS and PRCS can significantly improve network performance when compared with the previous solutions, in terms of packet delivery ratio, average energy consumption and end-to-end delay.

  16. Voluntary strategy suppresses the positive impact of preferential selection in prisoner’s dilemma

    NASA Astrophysics Data System (ADS)

    Sun, Lei; Lin, Pei-jie; Chen, Ya-shan

    2014-11-01

    Impact of aspiration is ubiquitous in social and biological disciplines. In this work, we try to explore the impact of such a trait on voluntary prisoners’ dilemma game via a selection parameter w. w=0 returns the traditional version of random selection. For positive w, the opponent of high payoff will be selected; while negative w means that the partner of low payoff will be chosen. We find that for positive w, cooperation will be greatly promoted in the interval of small b, at variance cooperation is inhibited with large b. For negative w, cooperation is fully restrained, irrespective of b value. It is found that the positive impact of preferential selection is suppressed by the voluntary strategy in prisoner’s dilemma. These observations can be supported by the spatial patterns. Our work may shed light on the emergence and persistence of cooperation with voluntary participation in social dilemma.

  17. Sexual selection on spontaneous mutations strengthens the between-sex genetic correlation for fitness.

    PubMed

    Allen, Scott L; McGuigan, Katrina; Connallon, Tim; Blows, Mark W; Chenoweth, Stephen F

    2017-10-01

    A proposed benefit to sexual selection is that it promotes purging of deleterious mutations from populations. For this benefit to be realized, sexual selection, which is usually stronger on males, must purge mutations deleterious to both sexes. Here, we experimentally test the hypothesis that sexual selection on males purges deleterious mutations that affect both male and female fitness. We measured male and female fitness in two panels of spontaneous mutation-accumulation lines of the fly, Drosophila serrata, each established from a common ancestor. One panel of mutation accumulation lines limited both natural and sexual selection (LS lines), whereas the other panel limited natural selection, but allowed sexual selection to operate (SS lines). Although mutation accumulation caused a significant reduction in male and female fitness in both the LS and SS lines, sexual selection had no detectable effect on the extent of the fitness reduction. Similarly, despite evidence of mutational variance for fitness in males and females of both treatments, sexual selection had no significant impact on the amount of mutational genetic variance for fitness. However, sexual selection did reshape the between-sex correlation for fitness: significantly strengthening it in the SS lines. After 25 generations, the between-sex correlation for fitness was positive but considerably less than one in the LS lines, suggesting that, although most mutations had sexually concordant fitness effects, sex-limited, and/or sex-biased mutations contributed substantially to the mutational variance. In the SS lines this correlation was strong and could not be distinguished from unity. Individual-based simulations that mimick the experimental setup reveal two conditions that may drive our results: (1) a modest-to-large fraction of mutations have sex-limited (or highly sex-biased) fitness effects, and (2) the average fitness effect of sex-limited mutations is larger than the average fitness effect of mutations that affect both sexes similarly. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  18. Artepillin C induces selective oxidative stress and inhibits migration and invasion in a comprehensive panel of human cervical cancer cell lines.

    PubMed

    Souza, Raquel Pantarotto; de Souza Bonfim-Mendonca, Patricia; Damke, Gabrielle Marconi Zago Ferreira; De Assis Carvalho, Analine Rosa Barquez; Ratti, Bianca Altrao; de Oliveira Dembogurski, Djaceli Sampaio; da Silva, Vania Ramos Sela; Silva, Sueli Oliveira; da Silva, Denise Brentan; Bruschi, Marcos Luciano; Maria-Engler, Silvya Stuchi; Consolaro, Marcia Edilaine Lopes

    2018-06-03

    Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer. To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A (HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells. Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV types. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. How Do Children Behave Regarding Their Birth Order in Dental Setting?

    PubMed

    Ghaderi, Faezeh; Fijan, Soleiman; Hamedani, Shahram

    2015-12-01

    Prediction of child cooperation level in dental setting is an important issue for a dentist to select the proper behavior management method. Many psychological studies have emphasized the effect of birth order on patient behavior and personality; however, only a few researches evaluated the effect of birth order on child's behavior in dental setting. This study was designed to evaluate the influence of children ordinal position on their behavior in dental setting. A total of 158 children with at least one primary mandibular molar needing class I restoration were selected. Children were classified based on the ordinal position; first, middle, or last child as well as single child. A blinded examiner recorded the pain perception of children during injection based on Visual Analogue Scale (VAS) and Sound, Eye and Movement (SEM) scale. To assess the child's anxiety, the questionnaire known as "Dental Subscale of the Children's Fear Survey Schedule" (CFSS-DS) was employed. The results showed that single children were significantly less cooperative and more anxious than the other children (p<0.001). The middle children were significantly more cooperative in comparison with the other child's position (p< 0.001). Single child may behave less cooperatively in dental setting. The order of child birth must also be considered in prediction of child's behavior for behavioral management.

  20. The impact of podcasting on the learning and satisfaction of undergraduate nursing students.

    PubMed

    Vogt, Marjorie; Schaffner, Barbara; Ribar, Alicia; Chavez, Ruth

    2010-01-01

    Nursing education has evolved from traditional pedagogical models to current methods using technology for knowledge acquisition. Podcasting is one example of teaching methodology used in higher education. Studies demonstrate positive student satisfaction with podcasting, but there is limited data related to knowledge acquisition. The purpose of this study was to examine the impact of podcasting on nursing student learning and satisfaction. Two classes of junior baccalaureate nursing students had scores on selected exam questions compared. The 2007 class (n=63) had select content presented in traditional lecture format where the 2008 class (n=57) had the same content presented via podcast. Both methods used the same faculty and exam questions. The 2008 class completed a satisfaction survey. Results indicated no significant difference in correct responses on exam questions. Exam scores were better with the first podcast, equal for the second, and worse with the third podcast. Students were overall satisfied with the podcasting experience and commented positively on its portability and flexibility. This study contributes to the knowledge base of podcasting effectiveness and raises the question of evaluation of new teaching methodologies. Must an increase in learning occur for new methods to be considered effective, or is positive student satisfaction adequate to encourage the adoption of new technology methods?

  1. Selective antitumor activity of roscovitine in head and neck cancer

    PubMed Central

    Biktasova, Asel; Bellinger, Gary; Yarbrough, Wendell G.; Issaeva, Natalia

    2016-01-01

    Radiation and chemotherapy that are commonly used to treat human cancers damage cellular DNA. DNA damage appears to be more toxic to cancer cells than normal cells, most likely due to deregulated checkpoint activation and/or deficiency in DNA repair pathways that are characteristics of many tumors. However, unwanted side effects arise as a result of DNA damage to normal cells during the treatment. Here, we show that roscovitine, a cyclin-dependent kinase (CDK) inhibitor that inhibits CDK-1, CDK-2, CDK-5, CDK-7, and CDK-9 due to competitive binding to the ATP site on the kinases, causes significant DNA damage followed by p53-dependent cell death in human papilloma virus (HPV)-positive, but not in HPV-negative, head and neck cancer cells. Since HPV positivity was a molecular marker for increased sensitivity of cells to roscovitine, we reasoned that systemic roscovitine administration would not be toxic to healthy HPV-negative tissue. Indeed, low roscovitine doses significantly inhibited the growth of HPV-associated xenografted tumors in mice without causing any detectable side effects. Given that inhibition of CDKs has been shown to inhibit replication of several viruses, we suggest that roscovitine treatment may represent a selective and safe targeted therapeutic option against HPV-positive head and neck cancer. PMID:27233076

  2. Urban Waste Recycling Behavior: Antecedents of Participation in a Selective Collection Program

    NASA Astrophysics Data System (ADS)

    Garcés, Conchita; Lafuente, Alberto; Pedraja, Marta; Rivera, Pilar

    2002-09-01

    The aim of this study is to analyze the antecedents of urban waste recycling behavior. To achieve this goal, a concrete urban waste management program was chosen. The study focuses on the Selective Collection Program (SCP) in Zaragoza, a medium-sized city in northeastern Spain. The research starts with a conceptual model in which the variables that potentially affect recycling behavior can be classified into two groups: incentives and barriers. Moreover, the sociodemographic characteristics of the individuals are included in our study. Given that the proposed model requires specification of latent variables or constructs, the analysis is based on the Structural Equation Models (SEM) methodology. The results revealed that environmental awareness, knowledge of the environmental impact of urban waste, and the positive perception of management by local government exercise a positive effect on individual recycling behavior, while perceived personal difficulties (space and time availability) and distance to and from the container have a negative effect. As regards sociodemographic variables, this study found that annual family income sustains a negative relationship with recycling behavior, while age maintains a positive one. The results obtained clearly show the important role that the public authorities play, especially municipal governments, in achieving the waste recycling objectives established in accordance with international legislation.

  3. Scientific citations favor positive results: a systematic review and meta-analysis.

    PubMed

    Duyx, Bram; Urlings, Miriam J E; Swaen, Gerard M H; Bouter, Lex M; Zeegers, Maurice P

    2017-08-01

    Citation bias concerns the selective citation of scientific articles based on their results. We brought together all available evidence on citation bias across scientific disciplines and quantified its impact. An extensive search strategy was applied to the Web of Science Core Collection and Medline, yielding 52 studies in total. We classified these studies on scientific discipline, selection method, and other variables. We also performed random-effects meta-analyses to pool the effect of positive vs. negative results on subsequent citations. Finally, we checked for other determinants of citation as reported in the citation bias literature. Evidence for the occurrence of citation bias was most prominent in the biomedical sciences and least in the natural sciences. Articles with statistically significant results were cited 1.6 (95% confidence interval [CI] 1.3-1.8) times more often than articles with nonsignificant results. Articles in which the authors explicitly conclude to have found support for their hypothesis were cited 2.7 (CI 2.0-3.7) times as often. Article results and journal impact factor were associated with citation more often than any other reported determinant. Similar to what we already know on publication bias, also citation bias can lead to an overrepresentation of positive results and unfounded beliefs. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Narrating positive versus negative memories of illness: does narrating influence the emotional tone of memories?

    PubMed

    Fioretti, C; Smorti, A

    2017-05-01

    Psychoncological studies have recognised a reduced autobiographical memory in cancer patients, furthermore cognitive studies have found that narrative is an effective instrument to re-elaborate memories. However, it is still unclear whether narrating positive versus negative events can have a different impact on autobiographical memory. The present study aims to explore the emotional experience of autobiographical memory before and after having narrated negative or positive events related to the illness. Of 63 oncological patients, 35 were selected for the present study. Participants completed a Memory Fluency Task twice, before and after having selected and narrated a positive (PN group) or a negative (NN group) memory of illness. They also had to attribute one or more emotions to each memory and to the narrative. The number of emotions and the percentage of emotional tones in both narrated and non-narrated memories were assessed. Narrated memories were more emotionally re-elaborated than non-narrated ones. Negative group participants, more than positive group ones, decreased negative emotions and increased complex ones. Authors discuss these results claiming that narrating works as a rehearsal of autobiographical memories in oncological patients and narrating negative memories eases the emotional re-elaboration of illness. © 2016 John Wiley & Sons Ltd.

  5. How motivation affects academic performance: a structural equation modelling analysis.

    PubMed

    Kusurkar, R A; Ten Cate, Th J; Vos, C M P; Westers, P; Croiset, G

    2013-03-01

    Few studies in medical education have studied effect of quality of motivation on performance. Self-Determination Theory based on quality of motivation differentiates between Autonomous Motivation (AM) that originates within an individual and Controlled Motivation (CM) that originates from external sources. To determine whether Relative Autonomous Motivation (RAM, a measure of the balance between AM and CM) affects academic performance through good study strategy and higher study effort and compare this model between subgroups: males and females; students selected via two different systems namely qualitative and weighted lottery selection. Data on motivation, study strategy and effort was collected from 383 medical students of VU University Medical Center Amsterdam and their academic performance results were obtained from the student administration. Structural Equation Modelling analysis technique was used to test a hypothesized model in which high RAM would positively affect Good Study Strategy (GSS) and study effort, which in turn would positively affect academic performance in the form of grade point averages. This model fit well with the data, Chi square = 1.095, df = 3, p = 0.778, RMSEA model fit = 0.000. This model also fitted well for all tested subgroups of students. Differences were found in the strength of relationships between the variables for the different subgroups as expected. In conclusion, RAM positively correlated with academic performance through deep strategy towards study and higher study effort. This model seems valid in medical education in subgroups such as males, females, students selected by qualitative and weighted lottery selection.

  6. Generation-specific incentives and disincentives for nurse faculty to remain employed.

    PubMed

    Tourangeau, Ann E; Wong, Matthew; Saari, Margaret; Patterson, Erin

    2015-05-01

    The aims of this paper are to: (1) describe work characteristics that nurse faculty report encourage them to remain in or leave their academic positions; and (2) determine if there are generational differences in work characteristics selected. Nurse faculty play key roles in preparing new nurses and graduate nurses. However, educational institutions are challenged to maintain full employment in faculty positions. A cross-sectional, descriptive survey design was employed. Ontario nurse faculty were asked to select, from a list, work characteristics that entice them to remain in or leave their faculty positions. Respondent data (n = 650) were collected using mailed surveys over four months in 2011. While preferred work characteristics differed across generations, the most frequently selected incentives enticing nurse faculty to stay were having: a supportive director/dean, reasonable workloads, supportive colleagues, adequate resources, manageable class sizes and work/life balance. The most frequently selected disincentives included: unmanageable workloads, unsupportive organizations, poor work environments, exposure to bullying, belittling and other types of incivility in the workplace and having an unsupportive director/dean. This research yields new and important knowledge about work characteristics that nurse faculty report shape their decisions to remain in or leave their current employment. Certain work characteristics were rated as important among all generations. Where similarities exist, broad strategies addressing work characteristics may effectively promote nurse faculty retention. However, where generational differences exist, retention-promoting strategies should target generation-specific preferences. © 2014 John Wiley & Sons Ltd.

  7. 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.

  8. Determination of Azimuth Angle at Burnout for Placing a Satellite Over a Selected Earth Position

    NASA Technical Reports Server (NTRS)

    Skopinski, T. H.; Johnson, Katherine G.

    1960-01-01

    Expressions are presented for relating the satellite position in the orbital plane with the projected latitude and longitude on a rotating earth surface. An expression is also presented for determining the azimuth angle at a given burnout position on the basis of a selected passage position on the earth's surface. Examples are presented of a satellite launched eastward and one launched westward, each passing over a selected position sometime after having completed three orbits. Incremental changes from the desired latitude and longitude due to the earth's oblateness are included in the iteration for obtaining the azimuth angles of the two examples. The results for both cases are then compared with those obtained from a computing program using an oblate rotating earth. Changes from the selected latitude and longitude resulting from incremental changes from the burn-out azimuth angle and latitude are also analyzed.

  9. Selective visual scaling of time-scale processes facilitates broadband learning of isometric force frequency tracking.

    PubMed

    King, Adam C; Newell, Karl M

    2015-10-01

    The experiment investigated the effect of selectively augmenting faster time scales of visual feedback information on the learning and transfer of continuous isometric force tracking tasks to test the generality of the self-organization of 1/f properties of force output. Three experimental groups tracked an irregular target pattern either under a standard fixed gain condition or with selectively enhancement in the visual feedback display of intermediate (4-8 Hz) or high (8-12 Hz) frequency components of the force output. All groups reduced tracking error over practice, with the error lowest in the intermediate scaling condition followed by the high scaling and fixed gain conditions, respectively. Selective visual scaling induced persistent changes across the frequency spectrum, with the strongest effect in the intermediate scaling condition and positive transfer to novel feedback displays. The findings reveal an interdependence of the timescales in the learning and transfer of isometric force output frequency structures consistent with 1/f process models of the time scales of motor output variability.

  10. Perceptions of similarity and response to selected comparison targets in type 2 diabetes.

    PubMed

    Arigo, Danielle; Smyth, Joshua M; Suls, Jerry M

    2015-01-01

    Social comparisons (i.e. self-evaluations relative to others) may affect motivation for diabetes self-care behaviours. Comparisons can have either positive or negative effects, but it is not clear what differentiates these responses. This study tested the effect of a patient's perceived similarity to a comparison target on motivation for self-care. Individuals with type 2 diabetes (n = 180, MA1c = 7.59%) selected to read one of four brief descriptions of a patient with diabetes. Participants rated their motivation for self-care behaviours prior and subsequent to reading and reported the extent to which they focused on similarities between the self and the selected patient while reading. Perceived similarity moderated the effect of selection on motivation for self-care (p = .01, η2 = .06). Increased motivation was observed if participants focused on similarities with patients 'doing better' (i.e. high coping effectiveness/low symptom severity) and decreased motivation if they focused on similarities with patients 'doing worse' (low coping effectiveness/high symptom severity). Providing social comparison information in diabetes management (and perhaps other chronic diseases) may improve motivation for self-care among some patients. A subset of patients, however, may benefit from guidance to focus on similarities with certain targets.

  11. Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

    PubMed

    Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

    2011-06-01

    Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

  12. Effect of MLC leaf position, collimator rotation angle, and gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma

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

    Bai, Sen; Li, Guangjun; Wang, Maojie

    The purpose of this study was to investigate the effect of multileaf collimator (MLC) leaf position, collimator rotation angle, and accelerator gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma. To compare dosimetric differences between the simulating plans and the clinical plans with evaluation parameters, 6 patients with nasopharyngeal carcinoma were selected for simulation of systematic and random MLC leaf position errors, collimator rotation angle errors, and accelerator gantry rotation angle errors. There was a high sensitivity to dose distribution for systematic MLC leaf position errors in response to field size. When the systematic MLC position errors weremore » 0.5, 1, and 2 mm, respectively, the maximum values of the mean dose deviation, observed in parotid glands, were 4.63%, 8.69%, and 18.32%, respectively. The dosimetric effect was comparatively small for systematic MLC shift errors. For random MLC errors up to 2 mm and collimator and gantry rotation angle errors up to 0.5°, the dosimetric effect was negligible. We suggest that quality control be regularly conducted for MLC leaves, so as to ensure that systematic MLC leaf position errors are within 0.5 mm. Because the dosimetric effect of 0.5° collimator and gantry rotation angle errors is negligible, it can be concluded that setting a proper threshold for allowed errors of collimator and gantry rotation angle may increase treatment efficacy and reduce treatment time.« less

  13. Testing Direct and Indirect Effects of Identity, Media Use, Cognitions, and Conversations on Self-Reported Physical Activity Among a Sample of Hispanic Adults.

    PubMed

    Wirtz, John G; Wang, Zongyuan; Kulpavarapos, Supathida

    2017-03-01

    This article presents the results of a study testing the direct and indirect effects of identity, media use, cognitions and conversations on physical activity (PA). The study was guided by the O-S-O-R model (Markus & Zajonc, 1985), and it used data collected from a sample of Hispanic adults (N = 268) living in the U.S. Southwest. Exercise identity and ethnic identity were defined as pre-orientations (O 1 ); use of PA-related media content was defined as the stimulus (S); reflective integration and conversations about PA-related media were post-orientations (O 2 ); and self-reported physical activity was the behavioral response (R). Structural equation modeling was used to analyze the data, and several compelling results emerged. Exercise identity had a significant positive direct effect on PA and PA-related media use, as well as a significant positive indirect effect on conversations about PA-related media. PA-related media use exerted a strong and significant positive effect on conversations about PA-related media, as well as a significant positive indirect effect on PA. Finally, conversations about PA-related media content had a significant positive direct effect on PA. The results indicate that identity acts as a filter influencing what media content are selected and that cognitions and conversations about media content can serve as a link between media use and health behavior. Key words: O-S-O-R model, physical activity, Hispanic adults, identity, media use, conversation.

  14. A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning.

    PubMed

    Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

    2015-10-30

    The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different metrics can significantly improve the positioning accuracy while preserving the efficiency in computational complexity typical of two-step algorithms.

  15. A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning

    PubMed Central

    Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

    2015-01-01

    The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different metrics can significantly improve the positioning accuracy while preserving the efficiency in computational complexity typical of two-step algorithms. PMID:26528984

  16. A New Direction of Cancer Classification: Positive Effect of Low-Ranking MicroRNAs.

    PubMed

    Li, Feifei; Piao, Minghao; Piao, Yongjun; Li, Meijing; Ryu, Keun Ho

    2014-10-01

    Many studies based on microRNA (miRNA) expression profiles showed a new aspect of cancer classification. Because one characteristic of miRNA expression data is the high dimensionality, feature selection methods have been used to facilitate dimensionality reduction. The feature selection methods have one shortcoming thus far: they just consider the problem of where feature to class is 1:1 or n:1. However, because one miRNA may influence more than one type of cancer, human miRNA is considered to be ranked low in traditional feature selection methods and are removed most of the time. In view of the limitation of the miRNA number, low-ranking miRNAs are also important to cancer classification. We considered both high- and low-ranking features to cover all problems (1:1, n:1, 1:n, and m:n) in cancer classification. First, we used the correlation-based feature selection method to select the high-ranking miRNAs, and chose the support vector machine, Bayes network, decision tree, k-nearest-neighbor, and logistic classifier to construct cancer classification. Then, we chose Chi-square test, information gain, gain ratio, and Pearson's correlation feature selection methods to build the m:n feature subset, and used the selected miRNAs to determine cancer classification. The low-ranking miRNA expression profiles achieved higher classification accuracy compared with just using high-ranking miRNAs in traditional feature selection methods. Our results demonstrate that the m:n feature subset made a positive impression of low-ranking miRNAs in cancer classification.

  17. Convergent Evolution of the Osmoregulation System in Decapod Shrimps.

    PubMed

    Yuan, Jianbo; Zhang, Xiaojun; Liu, Chengzhang; Duan, Hu; Li, Fuhua; Xiang, Jianhai

    2017-02-01

    In adaptating to different aquatic environments, seawater (SW) and freshwater (FW) shrimps have exploited different adaptation strategies, which should generate clusters of genes with different adaptive features. However, little is known about the genetic basis of these physiological adaptations. Thus, in this study, we performed comparative transcriptomics and adaptive evolution analyses on SW and FW shrimps and found that convergent evolution may have happened on osmoregulation system of shrimps. We identified 275 and 234 positively selected genes in SW and FW shrimps, respectively, which enriched in the functions of ion-binding and membrane-bounded organelles. Among them, five (CaCC, BEST2, GPDH, NKA, and Integrin) and four (RasGAP, RhoGDI, CNK3, and ODC) osmoregulation-related genes were detected in SW and FW shrimps, respectively. All five genes in SW shrimps have been reported to have positive effects on ion transportation, whereas RasGAP and RhoGDI in FW shrimps are associated with negative control of ion transportation, and CNK3 and ODC play central roles in cation homeostasis. Besides, the phylogenetic tree reconstructed from the positively selected sites separated the SW and FW shrimps into two groups. Distinct subsets of parallel substitutions also have been found in these osmoregulation-related genes in SW and FW shrimps. Therefore, our results suggest that distinct convergent evolution may have occurred in the osmoregulation systems of SW and FW shrimps. Furthermore, positive selection of osmoregulation-related genes may be beneficial for the regulation of water and salt balance in decapod shrimps.

  18. Economic evaluation of different screening alternatives for patients with clinically suspected acute deep vein thrombosis.

    PubMed

    Bogavac-Stanojević, Natasa; Dopsaj, Violeta; Jelić-Ivanović, Zorana; Lakić, Dragana; Vasić, Dragan; Petrova, Guenka

    2013-01-01

    We examined the cost-effectiveness of the three different D-dimer measurements in the screening of DVT in models with and without calculation of pre-test probability (PTP) score. Moreover, we calculated the minimal cost in DVT detection. In the group of 192 patients with clinically suspected acute DVT, we examined the three different D-dimer measurements (Innovance D-dimer, Hemosil D-dimer HS and Vidas D-dimer Exclusion II) in combination with and without PTP assessment. The diagnostic alternative employing Vidas D-dimer Exclusion II assay without and with PTP calculation gave lower incremental cost-effectiveness ratio (ICER) than the alternative employing Hemosil D-dimer HS assay (0.187 Euros vs. 0.998 Euros per one additional DVT positive patient selected for CUS in model without PTP assessment and 0.450 vs. 0.753 Euros per one DVT positive patient selected for CUS in model with PTP assessment). According to sensitivity analysis, the Hemosil D-dimer HS assay was the most cost effective alternative when one patient was admitted to the vascular ambulance per day. Vidas D-dimer Exclusion II assay was the most cost effective alternative when more than one patient were admitted to the vascular ambulance per day. Cost minimisation analysis indicated that selection of patients according to PTP score followed by D-dimer analysis decreases the cost of DVT diagnosis. ICER analysis enables laboratories to choose optimal laboratory tests according to number of patients admitted to laboratory. Results support the feasibility of using PTP scoring and D-dimer measurement before CUS examination in DVT screening.

  19. Ceftazidime Is the Key Diversification and Selection Driver of VIM-Type Carbapenemases.

    PubMed

    Martínez-García, Laura; González-Alba, José M; Baquero, Fernando; Cantón, Rafael; Galán, Juan Carlos

    2018-05-08

    In recent decades, carbapenems have been considered the last line of antibiotic therapy for Gram-negative bacterial infections. Unfortunately, strains carrying a high diversity of β-lactamases able to hydrolyze carbapenems have emerged in the clinical setting. Among them, VIM β-lactamases have diversified in a bloom of variants. The evolutionary reconstructions performed in this work revealed that, at the end of the 1980s, two independent events involving diversification from VIM-2 and VIM-4 produced at least 25 VIM variants. Later, a third event involving diversification from VIM-1 occurred in the mid-1990s. In a second approach to understanding the emergence of VIM carbapenemases, 44 mutants derived from VIM-2 and VIM-4 were obtained by site-directed mutagenesis based on those positions predicted to be under positive selection. These variants were expressed in an isogenic context. The more-evolved variants yielded increased levels of hydrolytic efficiency toward ceftazidime to a higher degree than toward carbapenems. In fact, an antagonist effect was frequently observed. These results led us to develop an experimental-evolution step. When Escherichia coli strains carrying VIM-2 or VIM-4 were submitted to serial passages at increasing concentrations of carbapenems or ceftazidime, more-efficient new variants (such as VIM-11 and VIM-1, with N165S [bearing a change from N to S at position 165] and R228S mutations, respectively) were only obtained when ceftazidime was present. Therefore, the observed effect of ceftazidime in the diversification and selection of VIM variants might help to explain the recent bloom of carbapenemase diversity, and it also represents another example of the potential universal effect exerted by ceftazidime in the selection of more-efficient β-lactamase variants, as in TEM, CTX-M, or KPC enzymes. IMPORTANCE One of the objectives recently proposed by the World Health Organization (WHO) Assembly in the global plan on antimicrobial resistance was to improve the understanding and knowledge of antimicrobial resistance. In the present work, we paid attention to the drivers of diversification and selection of new carbapenemases in Gram-negative bacteria, which occupy one of the most critical places in the WHO priority list of antibiotic-resistant microorganisms. Based on evolutionary-reconstruction, site-directed-mutagenesis, and experimental-evolution approaches, we proposed a critical role of ceftazidime exposure in the selection of VIM carbapenemase variants. This surprising finding is also applicable to other β-lactamases, indicating that ceftazidime, and not other antibiotics, might have a universal effect in the diversification of β-lactamases. Our results might help to define future strategies to reconsider the extended use of ceftazidime. Copyright © 2018 Martínez-García et al.

  20. Emotion effects on implicit and explicit musical memory in normal aging.

    PubMed

    Narme, Pauline; Peretz, Isabelle; Strub, Marie-Laure; Ergis, Anne-Marie

    2016-12-01

    Normal aging affects explicit memory while leaving implicit memory relatively spared. Normal aging also modifies how emotions are processed and experienced, with increasing evidence that older adults (OAs) focus more on positive information than younger adults (YAs). The aim of the present study was to investigate how age-related changes in emotion processing influence explicit and implicit memory. We used emotional melodies that differed in terms of valence (positive or negative) and arousal (high or low). Implicit memory was assessed with a preference task exploiting exposure effects, and explicit memory with a recognition task. Results indicated that effects of valence and arousal interacted to modulate both implicit and explicit memory in YAs. In OAs, recognition was poorer than in YAs; however, recognition of positive and high-arousal (happy) studied melodies was comparable. Insofar as socioemotional selectivity theory (SST) predicts a preservation of the recognition of positive information, our findings are not fully consistent with the extension of this theory to positive melodies since recognition of low-arousal (peaceful) studied melodies was poorer in OAs. In the preference task, YAs showed stronger exposure effects than OAs, suggesting an age-related decline of implicit memory. This impairment is smaller than the one observed for explicit memory (recognition), extending to the musical domain the dissociation between explicit memory decline and implicit memory relative preservation in aging. Finally, the disproportionate preference for positive material seen in OAs did not translate into stronger exposure effects for positive material suggesting no age-related emotional bias in implicit memory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Collective feature selection to identify crucial epistatic variants.

    PubMed

    Verma, Shefali S; Lucas, Anastasia; Zhang, Xinyuan; Veturi, Yogasudha; Dudek, Scott; Li, Binglan; Li, Ruowang; Urbanowicz, Ryan; Moore, Jason H; Kim, Dokyoon; Ritchie, Marylyn D

    2018-01-01

    Machine learning methods have gained popularity and practicality in identifying linear and non-linear effects of variants associated with complex disease/traits. Detection of epistatic interactions still remains a challenge due to the large number of features and relatively small sample size as input, thus leading to the so-called "short fat data" problem. The efficiency of machine learning methods can be increased by limiting the number of input features. Thus, it is very important to perform variable selection before searching for epistasis. Many methods have been evaluated and proposed to perform feature selection, but no single method works best in all scenarios. We demonstrate this by conducting two separate simulation analyses to evaluate the proposed collective feature selection approach. Through our simulation study we propose a collective feature selection approach to select features that are in the "union" of the best performing methods. We explored various parametric, non-parametric, and data mining approaches to perform feature selection. We choose our top performing methods to select the union of the resulting variables based on a user-defined percentage of variants selected from each method to take to downstream analysis. Our simulation analysis shows that non-parametric data mining approaches, such as MDR, may work best under one simulation criteria for the high effect size (penetrance) datasets, while non-parametric methods designed for feature selection, such as Ranger and Gradient boosting, work best under other simulation criteria. Thus, using a collective approach proves to be more beneficial for selecting variables with epistatic effects also in low effect size datasets and different genetic architectures. Following this, we applied our proposed collective feature selection approach to select the top 1% of variables to identify potential interacting variables associated with Body Mass Index (BMI) in ~ 44,000 samples obtained from Geisinger's MyCode Community Health Initiative (on behalf of DiscovEHR collaboration). In this study, we were able to show that selecting variables using a collective feature selection approach could help in selecting true positive epistatic variables more frequently than applying any single method for feature selection via simulation studies. We were able to demonstrate the effectiveness of collective feature selection along with a comparison of many methods in our simulation analysis. We also applied our method to identify non-linear networks associated with obesity.

  2. 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.

  3. 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

  4. Single substitutions to closely related amino acids contribute to the functional diversification of an insect-inducible, positively selected plant cystatin.

    PubMed

    Rasoolizadeh, Asieh; Goulet, Marie-Claire; Sainsbury, Frank; Cloutier, Conrad; Michaud, Dominique

    2016-04-01

    A causal link has been reported between positively selected amino acids in plant cystatins and the inhibitory range of these proteins against insect digestive cysteine (Cys) proteases. Here we assessed the impact of single substitutions to closely related amino acids on the contribution of positive selection to cystatin diversification. Cystatin sequence alignments, while confirming hypervariability, indicated a preference for related amino acids at positively selected sites. For example, the non-polar residues leucine (Leu), isoleucine (Ile) and valine (Val) were shown to predominate at positively selected site 2 in the N-terminal region, unlike selected sites 6 and 10, where polar residues are preferred. The model cystatin SlCYS8 and single variants with Leu, Ile or Val at position 2 were compared with regard to their ability to bind digestive proteases of the coleopteran pest Leptinotarsa decemlineata and to induce compensatory responses in this insect. A functional proteomics procedure to capture target Cys proteases in midgut extracts allowed confirmation of distinct binding profiles for the cystatin variants. A shotgun proteomics procedure to monitor whole Cys protease complements revealed protease family specific compensatory responses in the insect, dependent on the variant ingested. Our data confirm the contribution of closely related amino acids to the functional diversity of positively selected plant cystatins in a broader structure/function context imposing physicochemical constraints to primary structure alterations. They also underline the complexity of protease/inhibitor interactions in plant-insect systems, and the challenges still to be met in order to harness the full potential of ectopically expressed protease inhibitors in crop protection. © 2016 Federation of European Biochemical Societies.

  5. Computational Analyses of an Evolutionary Arms Race between Mammalian Immunity Mediated by Immunoglobulin A and Its Subversion by Bacterial Pathogens

    PubMed Central

    Pinheiro, Ana; Woof, Jenny M.; Abi-Rached, Laurent; Parham, Peter; Esteves, Pedro J.

    2013-01-01

    IgA is the predominant immunoglobulin isotype in mucosal tissues and external secretions, playing important roles both in defense against pathogens and in maintenance of commensal microbiota. Considering the complexity of its interactions with the surrounding environment, IgA is a likely target for diversifying or positive selection. To investigate this possibility, the action of natural selection on IgA was examined in depth with six different methods: CODEML from the PAML package and the SLAC, FEL, REL, MEME and FUBAR methods implemented in the Datamonkey webserver. In considering just primate IgA, these analyses show that diversifying selection targeted five positions of the Cα1 and Cα2 domains of IgA. Extending the analysis to include other mammals identified 18 positively selected sites: ten in Cα1, five in Cα2 and three in Cα3. All but one of these positions display variation in polarity and charge. Their structural locations suggest they indirectly influence the conformation of sites on IgA that are critical for interaction with host IgA receptors and also with proteins produced by mucosal pathogens that prevent their elimination by IgA-mediated effector mechanisms. Demonstrating the plasticity of IgA in the evolution of different groups of mammals, only two of the eighteen selected positions in all mammals are included in the five selected positions in primates. That IgA residues subject to positive selection impact sites targeted both by host receptors and subversive pathogen ligands highlights the evolutionary arms race playing out between mammals and pathogens, and further emphasizes the importance of IgA in protection against mucosal pathogens. PMID:24019941

  6. Effects of feature-selective and spatial attention at different stages of visual processing.

    PubMed

    Andersen, Søren K; Fuchs, Sandra; Müller, Matthias M

    2011-01-01

    We investigated mechanisms of concurrent attentional selection of location and color using electrophysiological measures in human subjects. Two completely overlapping random dot kinematograms (RDKs) of two different colors were presented on either side of a central fixation cross. On each trial, participants attended one of these four RDKs, defined by its specific combination of color and location, in order to detect coherent motion targets. Sustained attentional selection while monitoring for targets was measured by means of steady-state visual evoked potentials (SSVEPs) elicited by the frequency-tagged RDKs. Attentional selection of transient targets and distractors was assessed by behavioral responses and by recording event-related potentials to these stimuli. Spatial attention and attention to color had independent and largely additive effects on the amplitudes of SSVEPs elicited in early visual areas. In contrast, behavioral false alarms and feature-selective modulation of P3 amplitudes to targets and distractors were limited to the attended location. These results suggest that feature-selective attention produces an early, global facilitation of stimuli having the attended feature throughout the visual field, whereas the discrimination of target events takes place at a later stage of processing that is only applied to stimuli at the attended position.

  7. Monoclonal antibodies with group specificity toward sulfonamides: selection of hapten and antibody selectivity.

    PubMed

    Wang, Zhanhui; Beier, Ross C; Sheng, Yajie; Zhang, Suxia; Jiang, Wenxiao; Wang, Zhaopeng; Wang, Jin; Shen, Jianzhong

    2013-05-01

    Immunoassays based on the current available antibodies for large multi-sulfonamide screening programs have suffered from high selectivity for individual sulfonamides and a wide range of selectivities for different sulfonamides. In this study, five synthesized haptens, HS, BS, CS, SA10, and TS and two sulfonamides, SG and SMX were used as haptens, which may or may not contain a ring structure at the N1 position of the sulfonamides, were selected to evaluate the effectiveness for producing group-specific monoclonal antibodies (MAbs). Mice immunized with three different two-ring haptens were used for hybridoma production, which resulted in three unique MAbs recognizing 10, 13, and 15 sulfonamides showing 50 % inhibition (IC50) at concentrations below 100 ng mL(-1). MAb 4D11 derived from one novel immunizing hapten could recognize 12 sulfonamides with IC50 values ranging from 1.2 to 12.4 ng mL(-1), almost within 1 order of magnitude. These produced MAbs show lower IC50 values in addition to significantly improved group specificity compared with previously generated MAbs. This study clearly indicates that the careful selection of the immunizing hapten has an important effect on the specificity of the generated antibodies.

  8. Spatial Resolution Effects of Digital Terrain Models on Landslide Susceptibility Analysis

    NASA Astrophysics Data System (ADS)

    Chang, K. T.; Dou, J.; Chang, Y.; Kuo, C. P.; Xu, K. M.; Liu, J. K.

    2016-06-01

    The purposes of this study are to identify the maximum number of correlated factors for landslide susceptibility mapping and to evaluate landslide susceptibility at Sihjhong river catchment in the southern Taiwan, integrating two techniques, namely certainty factor (CF) and artificial neural network (ANN). The landslide inventory data of the Central Geological Survey (CGS, MOEA) in 2004-2014 and two digital elevation model (DEM) datasets including a 5-meter LiDAR DEM and a 30-meter Aster DEM were prepared. We collected thirteen possible landslide-conditioning factors. Considering the multi-collinearity and factor redundancy, we applied the CF approach to optimize these thirteen conditioning factors. We hypothesize that if the CF values of the thematic factor layers are positive, it implies that these conditioning factors have a positive relationship with the landslide occurrence. Therefore, based on this assumption and positive CF values, seven conditioning factors including slope angle, slope aspect, elevation, terrain roughness index (TRI), terrain position index (TPI), total curvature, and lithology have been selected for further analysis. The results showed that the optimized-factors model provides a better accuracy for predicting landslide susceptibility in the study area. In conclusion, the optimized-factors model is suggested for selecting relative factors of landslide occurrence.

  9. 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).

  10. 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

  11. Synthesis of the PPARbeta/delta-selective agonist GW501516 and C4-thiazole-substituted analogs.

    PubMed

    Pereira, Raquel; Gaudon, Claudine; Iglesias, Beatriz; Germain, Pierre; Gronemeyer, Hinrich; de Lera, Angel R

    2006-01-01

    Sequential, position-selective, Pd-catalyzed cross-coupling reactions of 2,4-dibromo-5-hydroxymethylthiazole provided the scaffold for the synthesis of GW501516, the most potent PPARbeta/delta agonist yet described, and equally selective analogs at the thiazole-C4 position.

  12. Differential effects of others' emotional cues on 18-month-olds' preferential reproduction of observed actions.

    PubMed

    Patzwald, Christiane; Curley, Charlotte A; Hauf, Petra; Elsner, Birgit

    2018-05-01

    Infants use others' emotional signals to regulate their own object-directed behavior and action reproduction, and they typically produce more actions after having observed positive as compared to negative emotional cues. This study explored infants' understanding of the referential specificity of others' emotional cues when being confronted with two actions that are accompanied by different emotional displays. Selective action reproduction was measured after 18-month-olds (N = 42) had observed two actions directed at the same object, one of which was modeled with a positive emotional expression and the other with a negative emotional expression. Across four trials with different objects, infants' first actions matched the positively-emoted actions more often than the negatively-emoted actions. In comparison with baseline-level, infants' initial performance changed only for the positively-emoted actions, in that it increased during test. Latencies to first object-touch during test did not differ when infants reproduced the positively- or negatively-emoted actions, respectively, indicating that infants related the cues to the respective actions rather than to the object. During demonstration, infants looked relatively longer at the object than at the model's face, with no difference in positive or negative displays. Infants during their second year of life thus capture the action-related referential specificity of others' emotional cues and seem to follow positive signals more readily when actively selecting which of two actions to reproduce preferentially. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Variation in promiscuity and sexual selection drives avian rate of Faster-Z evolution.

    PubMed

    Wright, Alison E; Harrison, Peter W; Zimmer, Fabian; Montgomery, Stephen H; Pointer, Marie A; Mank, Judith E

    2015-03-01

    Higher rates of coding sequence evolution have been observed on the Z chromosome relative to the autosomes across a wide range of species. However, despite a considerable body of theory, we lack empirical evidence explaining variation in the strength of the Faster-Z Effect. To assess the magnitude and drivers of Faster-Z Evolution, we assembled six de novo transcriptomes, spanning 90 million years of avian evolution. Our analysis combines expression, sequence and polymorphism data with measures of sperm competition and promiscuity. In doing so, we present the first empirical evidence demonstrating the positive relationship between Faster-Z Effect and measures of promiscuity, and therefore variance in male mating success. Our results from multiple lines of evidence indicate that selection is less effective on the Z chromosome, particularly in promiscuous species, and that Faster-Z Evolution in birds is due primarily to genetic drift. Our results reveal the power of mating system and sexual selection in shaping broad patterns in genome evolution. © 2015 John Wiley & Sons Ltd.

  14. Nonmaternal Care’s Association With Mother’s Parenting Sensitivity: A Case of Self-Selection Bias?

    PubMed Central

    Nomaguchi, Kei M.; DeMaris, Alfred

    2013-01-01

    Although attachment theory posits that the use of nonmaternal care undermines quality of mothers’ parenting, empirical evidence for this link is inconclusive. Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,233), the authors examined the associations between nonmaternal care characteristics and maternal sensitivity during the first 3 years of children’s lives, with special attention to selection effects and moderation by resource levels. Findings from fixed-effects regression models suggested that, on average, there is little relationship between nonmaternal care characteristics and maternal sensitivity, once selection factors are held constant. Some evidence of moderation effects was found, however. Excellent-quality care is related to more sensitivity for mothers with lower family income. Poor-quality care is related to lower sensitivity for single mothers, but not partnered mothers. In sum, nonmaternal care characteristics do not seem to have as much influence on mothers’ parenting as attachment theory claims. PMID:23772093

  15. Tilted seat position for non-ambulant individuals with neurological and neuromuscular impairment: a systematic review

    PubMed Central

    Porter, D; Pountney, TE

    2008-01-01

    Objective: To determine the effects of tilt-in-space seating on outcomes for people with neurological or neuromuscular impairment who cannot walk. Data sources: Search through electronic databases (MEDLINE, Embase, CINAHL, AMED). Discussions with researchers who are active in field. Review methods: Selection criteria included interventional studies that investigated the effects of seat tilt on outcome or observational studies that identified outcomes for those who had used tilt-in-space seating in populations with neurological or neuromuscular impairments. Two reviewers independently selected trials for inclusion, assessed quality and extracted data. Results: Nineteen studies were identified which fulfilled the selection criteria. Seventeen of these were essentially before–after studies investigating the immediate effects of tilting the seating. All studies looked at populations with neurological impairment, and most were on children with cerebral palsy (n = 8) or adults with spinal cord injury (n = 8). Reviewer's conclusion: Posterior tilt can reduce pressures at the interface under the pelvis. PMID:18042602

  16. The dark side of incremental learning: a model of cumulative semantic interference during lexical access in speech production.

    PubMed

    Oppenheim, Gary M; Dell, Gary S; Schwartz, Myrna F

    2010-02-01

    Naming a picture of a dog primes the subsequent naming of a picture of a dog (repetition priming) and interferes with the subsequent naming of a picture of a cat (semantic interference). Behavioral studies suggest that these effects derive from persistent changes in the way that words are activated and selected for production, and some have claimed that the findings are only understandable by positing a competitive mechanism for lexical selection. We present a simple model of lexical retrieval in speech production that applies error-driven learning to its lexical activation network. This model naturally produces repetition priming and semantic interference effects. It predicts the major findings from several published experiments, demonstrating that these effects may arise from incremental learning. Furthermore, analysis of the model suggests that competition during lexical selection is not necessary for semantic interference if the learning process is itself competitive. Copyright 2009 Elsevier B.V. All rights reserved.

  17. The importance of protein in leaf selection of folivorous primates.

    PubMed

    Ganzhorn, Joerg U; Arrigo-Nelson, Summer J; Carrai, Valentina; Chalise, Mukesh K; Donati, Giuseppe; Droescher, Iris; Eppley, Timothy M; Irwin, Mitchell T; Koch, Flávia; Koenig, Andreas; Kowalewski, Martin M; Mowry, Christopher B; Patel, Erik R; Pichon, Claire; Ralison, Jose; Reisdorff, Christoph; Simmen, Bruno; Stalenberg, Eleanor; Starrs, Danswell; Terboven, Juana; Wright, Patricia C; Foley, William J

    2017-04-01

    Protein limitation has been considered a key factor in hypotheses on the evolution of life history and animal communities, suggesting that animals should prioritize protein in their food choice. This contrasts with the limited support that food selection studies have provided for such a priority in nonhuman primates, particularly for folivores. Here, we suggest that this discrepancy can be resolved if folivores only need to select for high protein leaves when average protein concentration in the habitat is low. To test the prediction, we applied meta-analyses to analyze published and unpublished results of food selection for protein and fiber concentrations from 24 studies (some with multiple species) of folivorous primates. To counter potential methodological flaws, we differentiated between methods analyzing total nitrogen and soluble protein concentrations. We used a meta-analysis to test for the effect of protein on food selection by primates and found a significant effect of soluble protein concentrations, but a non-significant effect for total nitrogen. Furthermore, selection for soluble protein was reinforced in forests where protein was less available. Selection for low fiber content was significant but unrelated to the fiber concentrations in representative leaf samples of a given forest. There was no relationship (either negative or positive) between the concentration of protein and fiber in the food or in representative samples of leaves. Overall our study suggests that protein selection is influenced by the protein availability in the environment, explaining the sometimes contradictory results in previous studies on protein selection. Am. J. Primatol. 79:e22550, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. 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.

  19. Index to Positions: A Selective List, 1969-1982.

    ERIC Educational Resources Information Center

    Staniford, Edward; Conn, Edith

    Positions taken by the Academic Senate for California Community Colleges (ASCCC) on selected topics are traced over the years 1969 through 1982. Chronological listings of ASCCC positions are provided for the following topics as compiled in 1980: academic standards, accreditation, credit and noncredit course policy, general education, grade policy,…

  20. Selection Pressure in CD8+ T-cell Epitopes in the pol Gene of HIV-1 Infected Individuals in Colombia. A Bioinformatic Approach

    PubMed Central

    Acevedo-Sáenz, Liliana; Ochoa, Rodrigo; Rugeles, Maria Teresa; Olaya-García, Patricia; Velilla-Hernández, Paula Andrea; Diaz, Francisco J.

    2015-01-01

    One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells. PMID:25803098

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