CenH3 evolution reflects meiotic symmetry as predicted by the centromere drive model

PubMed Central

Zedek, František; Bureš, Petr

2016-01-01

The centromere drive model explaining rapid evolution of eukaryotic centromeres predicts higher frequency of positive selection acting on centromeric histone H3 (CenH3) in clades with asymmetric meiosis compared to the clades with only symmetric meiosis. However, despite the impression one might get from the literature, this key prediction of the centromere drive model has not only never been confirmed, but it has never been tested, because all the previous studies dealt only with the presence or absence instead of the frequency of positive selection. To provide evidence for or against different frequencies of positively selected CenH3 in asymmetrics and symmetrics, we have inferred the selective pressures acting on CenH3 in seventeen eukaryotic clades, including plants, animals, fungi, ciliates and apicomplexa, using codon-substitution models, and compared the inferred frequencies between asymmetrics and symmetrics in a quantitative manner. We have found that CenH3 has been evolving adaptively much more frequently in clades with asymmetric meiosis compared with clades displaying only symmetric meiosis which confirms the prediction of centromere drive model. Our findings indicate that the evolution of asymmetric meiosis required CenH3 to evolve adaptively more often to counterbalance the negative consequences of centromere drive. PMID:27629066

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.

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

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

PubMed

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

2016-06-01

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

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

PubMed Central

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

2016-01-01

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

Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

PubMed

Stephan, Wolfgang

2016-01-01

In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

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.

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

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.

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).

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

The roles of gene duplication, gene conversion and positive selection in rodent Esp and Mup pheromone gene families with comparison to the Abp family.

PubMed

Karn, Robert C; Laukaitis, Christina M

2012-01-01

Three proteinaceous pheromone families, the androgen-binding proteins (ABPs), the exocrine-gland secreting peptides (ESPs) and the major urinary proteins (MUPs) are encoded by large gene families in the genomes of Mus musculus and Rattus norvegicus. We studied the evolutionary histories of the Mup and Esp genes and compared them with what is known about the Abp genes. Apparently gene conversion has played little if any role in the expansion of the mouse Class A and Class B Mup genes and pseudogenes, and the rat Mups. By contrast, we found evidence of extensive gene conversion in many Esp genes although not in all of them. Our studies of selection identified at least two amino acid sites in β-sheets as having evolved under positive selection in the mouse Class A and Class B MUPs and in rat MUPs. We show that selection may have acted on the ESPs by determining K(a)/K(s) for Exon 3 sequences with and without the converted sequence segment. While it appears that purifying selection acted on the ESP signal peptides, the secreted portions of the ESPs probably have undergone much more rapid evolution. When the inner gene converted fragment sequences were removed, eleven Esp paralogs were present in two or more pairs with K(a)/K(s) >1.0 and thus we propose that positive selection is detectable by this means in at least some mouse Esp paralogs. We compare and contrast the evolutionary histories of all three mouse pheromone gene families in light of their proposed functions in mouse communication.

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

Absence of positive selection on CenH3 in Luzula suggests that holokinetic chromosomes may suppress centromere drive.

PubMed

Zedek, František; Bureš, Petr

2016-12-01

The centromere drive theory explains diversity of eukaryotic centromeres as a consequence of the recurrent conflict between centromeric repeats and centromeric histone H3 (CenH3), in which selfish centromeres exploit meiotic asymmetry and CenH3 evolves adaptively to counterbalance deleterious consequences of driving centromeres. Accordingly, adaptively evolving CenH3 has so far been observed only in eukaryotes with asymmetric meiosis. However, if such evolution is a consequence of centromere drive, it should depend not only on meiotic asymmetry but also on monocentric or holokinetic chromosomal structure. Selective pressures acting on CenH3 have never been investigated in organisms with holokinetic meiosis despite the fact that holokinetic chromosomes have been hypothesized to suppress centromere drive. Therefore, the present study evaluates selective pressures acting on the CenH3 gene in holokinetic organisms for the first time, specifically in the representatives of the plant genus Luzula (Juncaceae), in which the kinetochore formation is not co-localized with any type of centromeric repeat. PCR, cloning and sequencing, and database searches were used to obtain coding CenH3 sequences from Luzula species. Codon substitution models were employed to infer selective regimes acting on CenH3 in Luzula KEY RESULTS: In addition to the two previously published CenH3 sequences from L. nivea, 16 new CenH3 sequences have been isolated from 12 Luzula species. Two CenH3 isoforms in Luzula that originated by a duplication event prior to the divergence of analysed species were found. No signs of positive selection acting on CenH3 in Luzula were detected. Instead, evidence was found that selection on CenH3 of Luzula might have been relaxed. The results indicate that holokinetism itself may suppress centromere drive and, therefore, holokinetic chromosomes might have evolved as a defence against centromere drive. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Color-selective attention need not be mediated by spatial attention.

PubMed

Andersen, Søren K; Müller, Matthias M; Hillyard, Steven A

2009-06-08

It is well-established that attention can select stimuli for preferential processing on the basis of non-spatial features such as color, orientation, or direction of motion. Evidence is mixed, however, as to whether feature-selective attention acts by increasing the signal strength of to-be-attended features irrespective of their spatial locations or whether it acts by guiding the spotlight of spatial attention to locations containing the relevant feature. To address this question, we designed a task in which feature-selective attention could not be mediated by spatial selection. Participants observed a display of intermingled dots of two colors, which rapidly and unpredictably changed positions, with the task of detecting brief intervals of reduced luminance of 20% of the dots of one or the other color. Both behavioral indices and electrophysiological measures of steady-state visual evoked potentials showed selectively enhanced processing of the attended-color items. The results demonstrate that feature-selective attention produces a sensory gain enhancement at early levels of the visual cortex that occurs without mediation by spatial attention.

The NASA competitive placement plan for positions GS-15 and below (including trades and labor positions)

NASA Technical Reports Server (NTRS)

1993-01-01

This plan provides the framework for selection based on merit from among the best qualified candidates available. Selections will be made without regard to political, religious, or labor organization affiliation or nonaffiliation, marital status, race, color, sex, national origin, nondisqualifying disability, or age. This plan does not guarantee promotion but rather ensures that all qualified available candidates receive fair and equitable consideration for positions filled under these competitive procedures. Announcing a vacancy under this plan is only one method of locating applicants for a position and can be used in conjunction with other methods. Subject to applicable law and regulation, selection of an individual to fill a position is the decision of management, as is the decision as to the method(s) to be used in identifying candidates. This plan is applicable to all NASA Installations. It covers all positions in the competitive service at (and below) the GS/GM-15 level (including all trades and labor positions), except positions in the Office of the Inspector General. The requirements herein are not intended to, nor should they be construed to limit in any way, the independent personnel authority of the Inspector General under the Inspector General Act, as Amended.

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

PubMed Central

2012-01-01

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

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

PubMed

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

2012-10-02

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

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

Characterization of the unique function of a reduced amide bond in a cytolytic peptide that acts on phospholipid membranes.

PubMed Central

Oh, J E; Lee, K H

2000-01-01

The incorporation of a reduced amide bond, psi(CH(2)NH), into peptide results in an increase in the net positive charge and the perturbation of alpha-helical structure. By using this characteristic of the reduced amide bond, we designed and synthesized novel pseudopeptides containing reduced amide bonds, which had a great selectivity between bacterial and mammalian cells. A structure-activity relationship study on pseudopeptides indicated that the decrease in alpha-helicity and the increase in net positive charge in the backbone, caused by the incorporation of a reduced amide bond into the peptide, both contributed to an improvement in the selectivity between lipid membranes with various surface charges. However, activity results in vitro indicated that a perturbation of alpha-helical structure rather than an increase in net positive charge in the backbone is more important in the selectivity between bacterial and mammalian cells. The present result revealed that the backbone of membrane-active peptides were important not only in maintaining the secondary structure for the interactions with lipid membranes but also in direct interactions with lipid membranes. The present study showed the unique function of a reduced amide bond in cytolytic peptides and a direction for developing novel anti-bacterial agents from cytolytic peptides that act on the lipid membrane of micro-organisms. PMID:11104671

Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.

PubMed

Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

2007-01-01

T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.

Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling

PubMed Central

Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

2007-01-01

Background T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Results Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusion The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death. PMID:17239257

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...

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...

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...

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...

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...

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

USGS Publications Warehouse

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.

PubMed

Fetterman, Christina D; Rannala, Bruce; Walter, Michael A

2008-09-24

Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. Consideration of selection pressures observed in conjunction with known functional information allowed prediction of residue function and refinement of domain boundaries. Identification of residues that differentiate orthologs and paralogs provided insight into the development and functional consequences of paralogs and forkhead subfamily composition differences among species. Overall we found that after gene duplication of forkhead family members, rapid differentiation and subsequent fixation of amino acid changes through negative selection has occurred.

Rapidly evolving zona pellucida domain proteins are a major component of the vitelline envelope of abalone eggs

PubMed Central

Aagaard, Jan E.; Yi, Xianhua; MacCoss, Michael J.; Swanson, Willie J.

2006-01-01

Proteins harboring a zona pellucida (ZP) domain are prominent components of vertebrate egg coats. Although less well characterized, the egg coat of the non-vertebrate marine gastropod abalone (Haliotis spp.) is also known to contain a ZP domain protein, raising the possibility of a common molecular basis of metazoan egg coat structures. Egg coat proteins from vertebrate as well as non-vertebrate taxa have been shown to evolve under positive selection. Studied most extensively in the abalone system, coevolution between adaptively diverging egg coat and sperm proteins may contribute to the rapid development of reproductive isolation. Thus, identifying the pattern of evolution among egg coat proteins is important in understanding the role these genes may play in the speciation process. The purpose of the present study is to characterize the constituent proteins of the egg coat [vitelline envelope (VE)] of abalone eggs and to provide preliminary evidence regarding how selection has acted on VE proteins during abalone evolution. A proteomic approach is used to match tandem mass spectra of peptides from purified VE proteins with abalone ovary EST sequences, identifying 9 of 10 ZP domain proteins as components of the VE. Maximum likelihood models of codon evolution suggest positive selection has acted among a subset of amino acids for 6 of these genes. This work provides further evidence of the prominence of ZP proteins as constituents of the egg coat, as well as the prominent role of positive selection in diversification of these reproductive proteins. PMID:17085584

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

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

Provider and patient perceptions of malaria rapid diagnostic test use in Nigeria: a cross-sectional evaluation.

PubMed

Mokuolu, Olugbenga A; Ajumobi, Olufemi O; Ntadom, Godwin N; Adedoyin, Olanrewaju T; Roberts, Alero A; Agomo, Chimere O; Edozieh, Kate U; Okafor, Henrietta U; Wammanda, Robinson D; Odey, Friday A; Maikore, Ibrahim K; Abikoye, Olatayo O; Alabi, Adekunle D; Amajoh, Chiomah; Audu, Bala M

2018-05-16

Nigeria commenced a phased programmatic deployment of rapid diagnostic tests (RDT) at the primary health care (PHC) facility levels since 2011. Despite various efforts, the national testing rate for malaria is still very low. The uptake of RDT has been variable. This study was undertaken to determine the provider and patient perceptions to RDT use at the PHC level in Nigeria with their implications for improving uptake and compliance. A cross-sectional survey was conducted in 120 randomly selected PHCs across six states, across the six-geopolitical zones of Nigeria in January 2013. Health facility staff interviews were conducted to assess health workers (HW) perception, prescription practices and determinants of RDT use. Patient exit interviews were conducted to assess patient perception of RDT from ten patients/caregivers who met the eligibility criterion and were consecutively selected in each PHC, and to determine HW's compliance with RDT test results indirectly. Community members, each selected by their ward development committees in each Local Government Area were recruited for focus group discussion on their perceptions to RDT use. Health workers would use RDT results because of confidence in RDT results (95.4%) and its reduction in irrational use of artemisinin-based combination therapy (ACT) (87.2%). However, in Enugu state, RDT was not used by health workers because of the pervasive notion RDT that results were inaccurate. Among the 1207 exit interviews conducted, 549 (45.5%) had received RDT test. Compliance rate (administering ACT to positive patients and withholding ACT from negative patients) from patient exit interviews was 90.2%. Among caregivers/patients who had RDT done, over 95% knew that RDT tested for malaria, felt it was necessary and liked the test. Age of patients less than 5 years (p = 0.04) and "high" educational status (p = 0.0006) were factors influencing HW's prescription of ACT to RDT negative patients. The study demonstrated positive perception to RDT use by HW and among community members with good compliance rate among health workers at the PHC level. This positive perception should be explored in improving the current low level of malaria testing in Nigeria while addressing the influence of age on HW administration of ACT to RDT negative cases.

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

Analysis of adaptive evolution in Lyssavirus genomes reveals pervasive diversifying selection during species diversification.

PubMed

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

2014-11-19

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

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

PubMed Central

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

2014-01-01

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

Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

PubMed

Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

2015-09-16

Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be genotype-specific or geographically tailored.

A self-excising beta-recombinase/six cassette for repetitive gene deletion and homokaryon purification in Neurospora crassa

USDA-ARS?s Scientific Manuscript database

In a previous study we developed a cassette employing a bacterial beta-recombinase acting on six recognition sequences (beta-rec/six), which allowed repetitive site-specific gene deletion and marker recycling in Neurospora crassa. However, only one positive selection marker was used in the cassette...

In one's own image: ethics and the reproduction of deafness.

PubMed

Johnston, Trevor

2005-01-01

The ethics of the use of genetic screening and reproductive technologies to select against and for deafness is presented. It is argued that insofar as deafness is a disability it is ethical to act in such a way as to avoid the conception or birth of children with genetic or congenital deafness. The discovery and recognition of signing deaf communities as cultural and linguistic communities (minorities) does not alter this basic ethical position, although the consequences of widespread application of this technology appears destined to lead to the eventual disappearance of these communities. The argument that acting to avoid deafness is unethical because it will lead to the elimination of a linguistic or cultural group (genocide or ethnocide) or conversely that acting to ensure deafness is ethical, if not praiseworthy, can only be sustained if deafness is not regarded as a disability at all. I argue that the premise that deafness is not a disability of some sort is false and thus the claim that genetic selection against deafness is unethical is untenable.

Whole-Genome Positive Selection and Habitat-Driven Evolution in a Shallow and a Deep-Sea Urchin

PubMed Central

Oliver, Thomas A.; Garfield, David A.; Manier, Mollie K.; Haygood, Ralph; Wray, Gregory A.; Palumbi, Stephen R.

2010-01-01

Comparisons of genomic sequence between divergent species can provide insight into the action of natural selection across many distinct classes of proteins. Here, we examine the extent of positive selection as a function of tissue-specific and stage-specific gene expression in two closely-related sea urchins, the shallow-water Strongylocentrotus purpuratus and the deep-sea Allocentrotus fragilis, which have diverged greatly in their adult but not larval habitats. Genes that are expressed specifically in adult somatic tissue have significantly higher dN/dS ratios than the genome-wide average, whereas those in larvae are indistinguishable from the genome-wide average. Testis-specific genes have the highest dN/dS values, whereas ovary-specific have the lowest. Branch-site models involving the outgroup S. franciscanus indicate greater selection (ωFG) along the A. fragilis branch than along the S. purpuratus branch. The A. fragilis branch also shows a higher proportion of genes under positive selection, including those involved in skeletal development, endocytosis, and sulfur metabolism. Both lineages are approximately equal in enrichment for positive selection of genes involved in immunity, development, and cell–cell communication. The branch-site models further suggest that adult-specific genes have experienced greater positive selection than those expressed in larvae and that ovary-specific genes are more conserved (i.e., experienced greater negative selection) than those expressed specifically in adult somatic tissues and testis. Our results chart the patterns of protein change that have occurred after habitat divergence in these two species and show that the developmental or functional context in which a gene acts can play an important role in how divergent species adapt to new environments. PMID:20935062

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster

PubMed Central

Corbett-Detig, Russell B.

2016-01-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. “Sensitive sites” have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. PMID:27343234

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster.

PubMed

Corbett-Detig, Russell B

2016-09-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. "Sensitive sites" have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. Copyright © 2016 by the Genetics Society of America.

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.

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

PubMed

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

2016-09-11

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

A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera

PubMed Central

Zayed, Amro; Whitfield, Charles W.

2008-01-01

Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating “Africanized” honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive selection, detected by contrasting genetic differentiation estimates (FST) between coding and noncoding SNPs. In native populations, SNPs in protein-coding regions had significantly higher FST estimates than those in noncoding regions, indicating adaptive evolution in the genome driven by positive selection. This signal of selection was associated with the expansion of honey bees from Africa into Western and Northern Europe, perhaps reflecting adaptation to temperate environments. We estimate that positive selection acted on a minimum of 852–1,371 genes or ≈10% of the bee's coding genome. We also detected positive selection associated with the invasion of African-derived honey bees in the New World. We found that introgression of European-derived alleles into Africanized bees was significantly greater for coding than noncoding regions. Our findings demonstrate that Africanized bees exploited the genetic diversity present from preexisting introductions in an adaptive way. Finally, we found a significant negative correlation between FST estimates and the local GC content surrounding coding SNPs, suggesting that AT-rich genes play an important role in adaptive evolution in the honey bee. PMID:18299560

A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera.

PubMed

Zayed, Amro; Whitfield, Charles W

2008-03-04

Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating "Africanized" honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive selection, detected by contrasting genetic differentiation estimates (F(ST)) between coding and noncoding SNPs. In native populations, SNPs in protein-coding regions had significantly higher F(ST) estimates than those in noncoding regions, indicating adaptive evolution in the genome driven by positive selection. This signal of selection was associated with the expansion of honey bees from Africa into Western and Northern Europe, perhaps reflecting adaptation to temperate environments. We estimate that positive selection acted on a minimum of 852-1,371 genes or approximately 10% of the bee's coding genome. We also detected positive selection associated with the invasion of African-derived honey bees in the New World. We found that introgression of European-derived alleles into Africanized bees was significantly greater for coding than noncoding regions. Our findings demonstrate that Africanized bees exploited the genetic diversity present from preexisting introductions in an adaptive way. Finally, we found a significant negative correlation between F(ST) estimates and the local GC content surrounding coding SNPs, suggesting that AT-rich genes play an important role in adaptive evolution in the honey bee.

Drought survival and reproduction impose contrasting selection pressures on maximum body size and sexual size dimorphism in a snake, Seminatrix pygaea.

PubMed

Winne, Christopher T; Willson, John D; Whitfield Gibbons, J

2010-04-01

The causes and consequences of body size and sexual size dimorphism (SSD) have been central questions in evolutionary ecology. Two, often opposing selective forces are suspected to act on body size in animals: survival selection and reproductive (fecundity and sexual) selection. We have recently identified a system where a small aquatic snake species (Seminatrix pygaea) is capable of surviving severe droughts by aestivating within dried, isolated wetlands. We tested the hypothesis that the lack of aquatic prey during severe droughts would impose significant survivorship pressures on S. pygaea, and that the largest individuals, particularly females, would be most adversely affected by resource limitation. Our findings suggest that both sexes experience selection against large body size during severe drought when prey resources are limited, as nearly all S. pygaea are absent from the largest size classes and maximum body size and SSD are dramatically reduced following drought. Conversely, strong positive correlations between maternal body size and reproductive success in S. pygaea suggest that females experience fecundity selection for large size during non-drought years. Collectively, our study emphasizes the dynamic interplay between selection pressures that act on body size and supports theoretical predictions about the relationship between body size and survivorship in ectotherms under conditions of resource limitation.

Dietary Variation and Evolution of Gene Copy Number among Dog Breeds

PubMed Central

Reiter, Taylor; Jagoda, Evelyn; Capellini, Terence D.

2016-01-01

Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs. PMID:26863414

Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

PubMed

Reiter, Taylor; Jagoda, Evelyn; Capellini, Terence D

2016-01-01

Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.

Correlational selection leads to genetic integration of body size and an attractive plumage trait in dark-eyed juncos.

PubMed

McGlothlin, Joel W; Parker, Patricia G; Nolan, Val; Ketterson, Ellen D

2005-03-01

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark-eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness in the tail or "tail white") are more attractive to females and dominant in aggressive encounters over resources. We used restricted maximum-likelihood analysis of a long-term dataset to measure the heritability of tail white and two components of body size (wing length and tail length), as well as genetic correlations between pairs of these traits. We then used multiple regression to assess directional, quadratic, and correlational selection as they acted on tail white and body size via four components of lifetime fitness (juvenile and adult survival, mating success, and fecundity). We found a positive genetic correlation between tail white and body size (as measured by wing length), which indicates past correlational selection. Correlational selection, which was largely due to sexual selection on males, was also found to be currently acting on the same pair of traits. Larger males with whiter tails sired young with more females, most likely due to a combination of female choice, which favors males with whiter tails, and male-male competition, which favors both tail white and larger body size. To our knowledge, this is the first study to show both genetic correlations between sexually selected traits and currently acting correlational sexual selection, and we suggest that correlational sexual selection frequently may be an important mechanism for maintaining the honesty of sexual signals.

Dietary adaptation of FADS genes in Europe varied across time and geography.

PubMed

Ye, Kaixiong; Gao, Feng; Wang, David; Bar-Yosef, Ofer; Keinan, Alon

2017-05-26

Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis of omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis is essential for individuals subsisting on LCPUFA-poor diets (for example, plant-based). Positive selection on FADS genes has been reported in multiple populations, but its cause and pattern in Europeans remain unknown. Here we demonstrate, using ancient and modern DNA, that positive selection acted on the same FADS variants both before and after the advent of farming in Europe, but on opposite (that is, alternative) alleles. Recent selection in farmers also varied geographically, with the strongest signal in southern Europe. These varying selection patterns concur with anthropological evidence of varying diets, and with the association of farming-adaptive alleles with higher FADS1 expression and thus enhanced LCPUFA biosynthesis. Genome-wide association studies reveal that farming-adaptive alleles not only increase LCPUFAs, but also affect other lipid levels and protect against several inflammatory diseases.

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

Small Molecules for Early Endosome-Specific Patch Clamping.

PubMed

Chen, Cheng-Chang; Butz, Elisabeth S; Chao, Yu-Kai; Grishchuk, Yulia; Becker, Lars; Heller, Stefan; Slaugenhaupt, Susan A; Biel, Martin; Wahl-Schott, Christian; Grimm, Christian

2017-07-20

To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles. The two compounds act rapidly, specifically, and are readily applicable in contrast to genetic approaches or previously used compounds such as vacuolin, which enlarges EE, RE, and LE/LY. We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously expressing CD11b+ lung-tissue macrophages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Promiscuity, sexual selection, and genetic diversity: a reply to Spurgin.

PubMed

Lifjeld, Jan T; Gohli, Jostein; Johnsen, Arild

2013-10-01

We recently reported a positive association between female promiscuity and genetic diversity across passerine birds, and launched the hypothesis that female promiscuity acts as a balancing selection, pressure maintaining genetic diversity in populations (Gohli et al.2013). Spurgin (2013) questions both our analyses and interpretations. While we agree that the hypothesis needs more comprehensive empirical testing, we find his specific points of criticism unjustified. In a more general perspective, we call for a more explicit recognition of female mating preferences as mechanisms of selection in population genetics theory. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

A comparison of selected public health criteria in milk from milk-shops and from a national distributor.

PubMed

O'Ferrall-Berndt, M More

2003-06-01

Selected public health criteria of pasteurised milk available to the consumer from milk-shops in a pre-defined area of Pretoria compared with a national distributor's milk was evaluated. Of the 135 milk samples purchased from milk-shops, 87% were not fit for human consumption on the basis of the minimum standards prescribed in the Foodstuffs, Cosmetics and Disinfectants Act, 1972 (Act 54 of1972). The national distributor's milk (n = 79) did not contain any pathogens, toxins nor inhibitory substances and passed all the criteria laid down in the Act. Even though milk-shop milk was sold as having been pasteurised, 38.5% of samples were alkaline phosphatase positive, indicating probable inadequate pasteurisation. Milk-shop milk quality varied between milk-shops and between sampling days and differed significantly (P < 0.05) from the national distributor's milk. Total aerobic plate and coliform counts were generally high for all milk-shop milk samples. Somatic cell counts of milk-shop milk differed significantly (P < 0.05) from the national distributor's milk. Escherichia coli was detected in 1 ml of 17% of milk-shop milk, 95% of which originated from milk which was alkaline phosphatase positive. Salmonella spp. could not be detected in 1 ml in any of the E. coli-positive milk tested. Staphylococcus aureus was isolated from 40% of milk-shop milk samples, and S. aureus enterotoxins from 7.8% of 51 cultures. Inhibitory substances were detected in 54.1% of milk-shop milk. The presence of inhibitory substances and the isolation of E. coli and S. aureus (some of which were able to produce enterotoxins) indicated potentially unsafe milk and poses a serious public health risk to consumers.

Natural selection reduced diversity on human y chromosomes.

PubMed

Wilson Sayres, Melissa A; Lohmueller, Kirk E; Nielsen, Rasmus

2014-01-01

The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.

Natural Selection Reduced Diversity on Human Y Chromosomes

PubMed Central

Wilson Sayres, Melissa A.; Lohmueller, Kirk E.; Nielsen, Rasmus

2014-01-01

The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area. PMID:24415951

Sexual selection and conflict as engines of ecological diversification.

PubMed

Bonduriansky, Russell

2011-12-01

Ecological diversification presents an enduring puzzle: how do novel ecological strategies evolve in organisms that are already adapted to their ecological niche? Most attempts to answer this question posit a primary role for genetic drift, which could carry populations through or around fitness "valleys" representing maladaptive intermediate phenotypes between alternative niches. Sexual selection and conflict are thought to play an ancillary role by initiating reproductive isolation and thereby facilitating divergence in ecological traits through genetic drift or local adaptation. Here, I synthesize theory and evidence suggesting that sexual selection and conflict could play a more central role in the evolution and diversification of ecological strategies through the co-optation of sexual traits for viability-related functions. This hypothesis rests on three main premises, all of which are supported by theory and consistent with the available evidence. First, sexual selection and conflict often act at cross-purposes to viability selection, thereby displacing populations from the local viability optimum. Second, sexual traits can serve as preadaptations for novel viability-related functions. Third, ancestrally sex-limited sexual traits can be transferred between sexes. Consequently, by allowing populations to explore a broad phenotypic space around the current viability optimum, sexual selection and conflict could act as powerful drivers of ecological adaptation and diversification.

Main processes of the Atlantic cold tongue interannual variability

NASA Astrophysics Data System (ADS)

Planton, Yann; Voldoire, Aurore; Giordani, Hervé; Caniaux, Guy

2018-03-01

The interannual variability of the Atlantic cold tongue (ACT) is studied by means of a mixed-layer heat budget analysis. A method to classify extreme cold and warm ACT events is proposed and applied to ten various analysis and reanalysis products. This classification allows 5 cold and 5 warm ACT events to be selected over the period 1982-2007. Cold (warm) ACT events are defined by the presence of negative (positive) sea surface temperature (SST) anomalies at the center of the equatorial Atlantic in late boreal spring, preceded by negative (positive) zonal wind stress anomalies in the western equatorial Atlantic. An ocean general circulation model capable of reconstructing the interannual variability of the ACT correctly is used to demonstrate that cold ACT events develop rapidly from May to June mainly due to intense cooling by vertical mixing and horizontal advection. The simulated cooling at the center of the basin is the result of the combined effects of non-local and local processes. The non-local process is an upwelling associated with an eastward-propagating Kelvin wave, which makes the mixed-layer more shallow and preconditions the upper layers to be cooled by an intense heat loss at the base of the mixed-layer, which is amplified by a stronger local injection of energy from the atmosphere. The early cooling by vertical mixing in March is also shown to be a good predictor of June cooling. In July, horizontal advection starts to warm the mixed-layer abnormally and damps SST anomalies. The advection anomalies, which result from changes in the horizontal temperature gradient, are associated in some cases with the propagation of Rossby waves along the equator. During warm ACT events, processes are reversed, generating positive SST anomalies: a downwelling Kelvin wave triggers stratification anomalies and mixed-layer depth anomalies, amplified by a weaker injection of energy from the atmosphere in May-June. In July, warm ACT events are abnormally cooled due to negative horizontal advection anomalies resulting from processes similar to those that occur during cold ACT events. This additional cooling process extends the period of cooling of the ACT, reducing SST anomalies.

Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase.

PubMed

Pontremoli, Chiara; Forni, Diego; Cagliani, Rachele; Pozzoli, Uberto; Riva, Stefania; Bravo, Ignacio G; Clerici, Mario; Sironi, Manuela

2017-10-01

The Old World (OW) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent-to-human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. We used a set of human- and rodent-derived viral sequences to investigate the evolutionary history underlying OW arenavirus speciation, as well as the more recent selective events that accompanied LASV spread in West Africa. We show that the viral RNA polymerase (L protein) was a major positive selection target in OW arenaviruses and during LASV out-of-Nigeria migration. No evidence of selection was observed for the glycoprotein, whereas positive selection acted on the nucleoprotein (NP) during LCMV speciation. Positively selected sites in L and NP are surrounded by highly conserved residues, and the bulk of the viral genome evolves under purifying selection. Several positively selected sites are likely to modulate viral replication/transcription. In both L and NP, structural features (solvent exposed surface area) are important determinants of site-wise evolutionary rate variation. By incorporating several rodent-derived sequences, we also performed an analysis of OW arenavirus codon adaptation to the human host. Results do not support a previously hypothesized role of codon adaptation in disease severity for non-Nigerian strains. In conclusion, L and NP represent the major selection targets and possible determinants of disease presentation; these results suggest that field surveys and experimental studies should primarily focus on these proteins. © 2017 John Wiley & Sons Ltd.

Molecular mechanisms of dominance evolution in Müllerian mimicry.

PubMed

Llaurens, V; Joron, M; Billiard, S

2015-12-01

Natural selection acting on dominance between adaptive alleles at polymorphic loci can be sufficiently strong for dominance to evolve. However, the molecular mechanisms underlying such evolution are generally unknown. Here, using Müllerian mimicry as a case-study for adaptive morphological variation, we present a theoretical analysis of the invasion of dominance modifiers altering gene expression through different molecular mechanisms. Toxic species involved in Müllerian mimicry exhibit warning coloration, and converge morphologically with other toxic species of the local community, due to positive frequency-dependent selection acting on these colorations. Polymorphism in warning coloration may be maintained by migration-selection balance with fine scale spatial heterogeneity. We modeled a dominance modifier locus altering the expression of the warning coloration locus, targeting one or several alleles, acting in cis or trans, and either enhancing or repressing expression. We confirmed that dominance could evolve when balanced polymorphism was maintained at the color locus. Dominance evolution could result from modifiers enhancing one allele specifically, irrespective of their linkage with the targeted locus. Nonspecific enhancers could also persist in populations, at frequencies tightly depending on their linkage with the targeted locus. Altogether, our results identify which mechanisms of expression alteration could lead to dominance evolution in polymorphic mimicry. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

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).

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

PubMed

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

2014-04-01

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

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.

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

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.

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.

Isolation of Persicaria minor sesquiterpene synthase promoter and its deletions for transgenic Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Omar, Aimi Farehah; Ismail, Ismanizan

2016-11-01

Sesquiterpene synthase (SS) catalyzes the formation of sesquiterpenes from farnesyl diphosphate (FDP) via carbocation intermediates. In this study, the promoter region of sesquiterpene synthase was isolated from Persicaria minor to identify possible cis-acting elements in the promoter. The full-length PmSS promoter of P. minor is 1824-bp sequences. The sequence was analyzed and several putative cis-acting regulatory elements were identified. Three cis-acting regulatory elements were selected for deletion analysis which are cis-acting element involved in wound responsiveness (WUN), cis - acting element involved in defense and stress responsiveness (TC) and cis-acting element involved in ABA responsiveness (ABRE). Series of deletions were conducted to assess the promoter activity producing three truncated fragments promoter; Prom 2 1606-bp, Prom 3 1144- bp, and Prom 4 921-bp. The full-length promoter and its deletion series were cloned into the pBGWFS7 vector which contain β-glucuronidase (GUS) gene and green fluorescent protein (GFP) as the reporter gene. All constructs were successfully transformed into Arabidopsis thaliana based on PCR of positive BASTA resistance plants.

The Patient Protection and Affordable Care Act: implications for pediatric pharmacy practice.

PubMed

Vallejos, Ximena; Benavides, Sandra

2013-01-01

The impact of the Patient Protection and Affordable Care Act on the pediatric health care landscape includes expanded health insurance coverage and health care delivery improvements by increasing implementation of patient-centered medical homes and accountable care organizations. These offer opportunities for pharmacists to assume responsibility for the medication-related needs of pediatric patients through pharmacotherapy selection, medication therapy management performance, and medication reconciliation at each transition of care. Medically complex children with at least 2 chronic disease states may be the target population. Studies demonstrating the positive outcomes and cost-effectiveness of pharmacists in pediatric ambulatory care settings are needed.

Herbivores modify selection on plant functional traits in a temperate rainforest understory.

PubMed

Salgado-Luarte, Cristian; Gianoli, Ernesto

2012-08-01

There is limited evidence regarding the adaptive value of plant functional traits in contrasting light environments. It has been suggested that changes in these traits in response to light availability can increase herbivore susceptibility. We tested the adaptive value of plant functional traits linked with carbon gain in contrasting light environments and also evaluated whether herbivores can modify selection on these traits in each light environment. In a temperate rainforest, we examined phenotypic selection on functional traits in seedlings of the pioneer tree Aristotelia chilensis growing in sun (canopy gap) and shade (forest understory) and subjected to either natural herbivory or herbivore exclusion. We found differential selection on functional traits depending on light environment. In sun, there was positive directional selection on photosynthetic rate and relative growth rate (RGR), indicating that selection favors competitive ability in a high-resource environment. Seedlings with high specific leaf area (SLA) and intermediate RGR were selected in shade, suggesting that light capture and conservative resource use are favored in the understory. Herbivores reduced the strength of positive directional selection acting on SLA in shade. We provide the first demonstration that natural herbivory rates can change the strength of selection on plant ecophysiological traits, that is, attributes whose main function is resource uptake. Research addressing the evolution of shade tolerance should incorporate the selective role of herbivores.

Patterns of population differentiation and natural selection on the celiac disease background risk network.

PubMed

Sams, Aaron; Hawks, John

2013-01-01

Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes.

PubMed

Karn, Robert C; Laukaitis, Christina M

2014-08-01

In the present article, we summarize two aspects of our work on mouse ABP (androgen-binding protein): (i) the sexual selection function producing incipient reinforcement on the European house mouse hybrid zone, and (ii) the mechanism behind the dramatic expansion of the Abp gene region in the mouse genome. Selection unifies these two components, although the ways in which selection has acted differ. At the functional level, strong positive selection has acted on key sites on the surface of one face of the ABP dimer, possibly to influence binding to a receptor. A different kind of selection has apparently driven the recent and rapid expansion of the gene region, probably by increasing the amount of Abp transcript, in one or both of two ways. We have shown previously that groups of Abp genes behave as LCRs (low-copy repeats), duplicating as relatively large blocks of genes by NAHR (non-allelic homologous recombination). The second type of selection involves the close link between the accumulation of L1 elements and the expansion of the Abp gene family by NAHR. It is probably predicated on an initial selection for increased transcription of existing Abp genes and/or an increase in Abp gene number providing more transcriptional sites. Either or both could increase initial transcript production, a quantitative change similar to increasing the volume of a radio transmission. In closing, we also provide a note on Abp gene nomenclature.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-10-01

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

Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: development and biopharmacological profiling of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor.

PubMed

Pisani, Leonardo; Muncipinto, Giovanni; Miscioscia, Teresa Fabiola; Nicolotti, Orazio; Leonetti, Francesco; Catto, Marco; Caccia, Carla; Salvati, Patricia; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passeleu, Celine; Carotti, Angelo

2009-11-12

In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.

Likelihood analysis of the chalcone synthase genes suggests the role of positive selection in morning glories (Ipomoea).

PubMed

Yang, Ji; Gu, Hongya; Yang, Ziheng

2004-01-01

Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoides, which are important for the pigmentation of flowers and act as attractants to pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. In morning glories (Ipomoea), five functional CHS genes (A-E) have been described. Phylogenetic analysis of the Ipomoea CHS gene family revealed that CHS A, B, and C experienced accelerated rates of amino acid substitution relative to CHS D and E. To examine whether the CHS genes of the morning glories underwent adaptive evolution, maximum-likelihood models of codon substitution were used to analyze the functional sequences in the Ipomoea CHS gene family. These models used the nonsynonymous/synonymous rate ratio (omega = d(N)/ d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio test suggested significant variation in selection pressure among amino acid sites, with a small proportion of them detected to be under positive selection along the branches ancestral to CHS A, B, and C. Positive Darwinian selection appears to have promoted the divergence of subfamily ABC and subfamily DE and is at least partially responsible for a rate increase following gene duplication.

Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage

PubMed Central

Narula, Gagandeep; Tse-Dinh, Yuk-Ching

2012-01-01

Bacterial and archaeal topoisomerase I display selectivity for a cytosine base 4 nt upstream from the DNA cleavage site. Recently, the solved crystal structure of Escherichia coli topoisomerase I covalently linked to a single-stranded oligonucleotide revealed that R169 and R173 interact with the cytosine base at the −4 position via hydrogen bonds while the phenol ring of Y177 wedges between the bases at the −4 and the −5 position. Substituting R169 to alanine changed the selectivity of the enzyme for the base at the −4 position from a cytosine to an adenine. The R173A mutant displayed similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity. Mutation of Y177 to serine or alanine rendered the enzyme inactive. Although mutation of each of these residues led to different outcomes, R169, R173 and Y177 work together to interact with a cytosine base at the −4 position to facilitate DNA cleavage. These strictly conserved residues might act after initial substrate binding as a Molecular Ruler to form a protein–DNA complex with the scissile phosphate positioned at the active site for optimal DNA cleavage by the tyrosine hydroxyl nucleophile to facilitate DNA cleavage in the reaction pathway. PMID:22833607

Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators.

PubMed

Kolarič, Anja; Švajger, Urban; Tomašič, Tihomir; Brox, Regine; Frank, Theresa; Minovski, Nikola; Tschammer, Nuska; Anderluh, Marko

2018-05-11

Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation. Para-methoxy substitution leads to functional antagonism, while para-chloro triggers agonism. Additionally, we discovered that chemotaxis is not completely correlated with G protein pathways. This is the first work in which we have on a series of compounds successfully demonstrated that it is possible to produce selective as well as dual-acting modulators of chemokine receptors, which is very promising for future research in the field of discovery of selective or dual modulators of chemokine receptors. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors.

PubMed

Iranshahi, Mehrdad; Chini, Maria Giovanna; Masullo, Milena; Sahebkar, Amirhossein; Javidnia, Azita; Chitsazian Yazdi, Mahsa; Pergola, Carlo; Koeberle, Andreas; Werz, Oliver; Pizza, Cosimo; Terracciano, Stefania; Piacente, Sonia; Bifulco, Giuseppe

2015-12-24

Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C5 (isopentenyl, 5-8), C10 (geranyl, 9-12), and C15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site.

Visible-light Homogeneous Photocatalytic Conversion of CO2 into CO in Aqueous Solutions with an Iron Catalyst.

PubMed

Rao, Heng; Bonin, Julien; Robert, Marc

2017-11-23

An iron-substituted tetraphenyl porphyrin bearing positively charged trimethylammonio groups at the para position of each phenyl ring catalyzes the photoinduced conversion of CO 2 . This complex is water soluble and acts as a molecular catalyst to selectively reduce CO 2 into CO under visible-light irradiation in aqueous solutions (acetonitrile/water=1:9 v/v) with the assistance of purpurin, a simple organic photosensitizer. CO is produced with a catalytic selectivity of 95 % and turnover number up to 120, illustrating the possibility of photocatalyzing the reduction of CO 2 in aqueous solution by using visible light, a simple organic sensitizer coupled to an amine as a sacrificial electron donor, and an earth-abundant metal-based molecular catalyst. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differing Impacts Of Market Concentration On Affordable Care Act Marketplace Premiums.

PubMed

Scheffler, Richard M; Arnold, Daniel R; Fulton, Brent D; Glied, Sherry A

2016-05-01

Recent increases in market concentration among health plans, hospitals, and medical groups raise questions about what impact such mergers are having on costs to consumers. We examined the impact of market concentration on the growth of health insurance premiums between 2014 and 2015 in two Affordable Care Act state-based Marketplaces: Covered California and NY State of Health. We measured health plan, hospital, and medical group market concentration using the well-known Herfindahl-Hirschman Index (HHI) and used a multivariate regression model to relate these measures to premium growth. Both states exhibited a positive association between hospital concentration and premium growth and a positive (but not statistically significant) association between medical group concentration and premium growth. Our results for health plan concentration differed between the two states: It was positively associated with premium growth in New York but negatively associated with premium growth in California. The health plan concentration finding in Covered California may be the result of its selectively contracting with health plans. Project HOPE—The People-to-People Health Foundation, Inc.

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

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

PubMed

Liu, Qingpo

2009-03-01

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

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

Evolution and inheritance of early embryonic patterning in D. simulans and D. sechellia

PubMed Central

Lott, Susan E.; Ludwig, Michael Z.; Kreitman, Martin

2010-01-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation which selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth ‘stripe allometry’) in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species D. simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the “margin of error” for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness PMID:21121913

Genomewide Scan Reveals Amplification of mdr1 as a Common Denominator of Resistance to Mefloquine, Lumefantrine, and Artemisinin in Plasmodium chabaudi Malaria Parasites▿†‡

PubMed Central

Borges, Sofia; Cravo, Pedro; Creasey, Alison; Fawcett, Richard; Modrzynska, Katarzyna; Rodrigues, Louise; Martinelli, Axel; Hunt, Paul

2011-01-01

Multidrug-resistant Plasmodium falciparum malaria parasites pose a threat to effective drug control, even to artemisinin-based combination therapies (ACTs). Here we used linkage group selection and Solexa whole-genome resequencing to investigate the genetic basis of resistance to component drugs of ACTs. Using the rodent malaria parasite P. chabaudi, we analyzed the uncloned progeny of a genetic backcross between the mefloquine-, lumefantrine-, and artemisinin-resistant mutant AS-15MF and a genetically distinct sensitive clone, AJ, following drug treatment. Genomewide scans of selection showed that parasites surviving each drug treatment bore a duplication of a segment of chromosome 12 (translocated to chromosome 04) present in AS-15MF. Whole-genome resequencing identified the size of the duplicated segment and its position on chromosome 4. The duplicated fragment extends for ∼393 kbp and contains over 100 genes, including mdr1, encoding the multidrug resistance P-glycoprotein homologue 1. We therefore show that resistance to chemically distinct components of ACTs is mediated by the same genetic mutation, highlighting a possible limitation of these therapies. PMID:21709099

Genome-Wide Analysis of PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) Genes in Plants Reveals the Eudicot-Wide PDAT Gene Expansion and Altered Selective Pressures Acting on the Core Eudicot PDAT Paralogs1[OPEN

PubMed Central

Pan, Xue; Peng, Fred Y.; Weselake, Randall J.

2015-01-01

PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) is an enzyme that catalyzes the transfer of a fatty acyl moiety from the sn-2 position of a phospholipid to the sn-3-position of sn-1,2-diacylglyerol, thus forming triacylglycerol and a lysophospholipid. Although the importance of PDAT in triacylglycerol biosynthesis has been illustrated in some previous studies, the evolutionary relationship of plant PDATs has not been studied in detail. In this study, we investigated the evolutionary relationship of the PDAT gene family across the green plants using a comparative phylogenetic framework. We found that the PDAT candidate genes are present in all examined green plants, including algae, lowland plants (a moss and a lycophyte), monocots, and eudicots. Phylogenetic analysis revealed the evolutionary division of the PDAT gene family into seven major clades. The separation is supported by the conservation and variation in the gene structure, protein properties, motif patterns, and/or selection constraints. We further demonstrated that there is a eudicot-wide PDAT gene expansion, which appears to have been mainly caused by the eudicot-shared ancient gene duplication and subsequent species-specific segmental duplications. In addition, selection pressure analyses showed that different selection constraints have acted on three core eudicot clades, which might enable paleoduplicated PDAT paralogs to either become nonfunctionalized or develop divergent expression patterns during evolution. Overall, our study provides important insights into the evolution of the plant PDAT gene family and explores the evolutionary mechanism underlying the functional diversification among the core eudicot PDAT paralogs. PMID:25585619

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

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

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).

An Approach to Greater Specificity for Glucocorticoids

PubMed Central

Chow, Carson C.; Simons, S. Stoney

2018-01-01

Glucocorticoid steroids are among the most prescribed drugs each year. Nonetheless, the many undesirable side effects, and lack of selectivity, restrict their greater usage. Research to increase glucocorticoid specificity has spanned many years. These efforts have been hampered by the ability of glucocorticoids to both induce and repress gene transcription and also by the lack of success in defining any predictable properties that control glucocorticoid specificity. Correlations of transcriptional specificity have been observed with changes in steroid structure, receptor and chromatin conformation, DNA sequence for receptor binding, and associated cofactors. However, none of these studies have progressed to the point of being able to offer guidance for increased specificity. We summarize here a mathematical theory that allows a novel and quantifiable approach to increase selectivity. The theory applies to all three major actions of glucocorticoid receptors: induction by agonists, induction by antagonists, and repression by agonists. Simple graphical analysis of competition assays involving any two factors (steroid, chemical, peptide, protein, DNA, etc.) yields information (1) about the kinetically described mechanism of action for each factor at that step where the factor acts in the overall reaction sequence and (2) about the relative position of that step where each factor acts. These two pieces of information uniquely provide direction for increasing the specificity of glucocorticoid action. Consideration of all three modes of action indicate that the most promising approach for increased specificity is to vary the concentrations of those cofactors/pharmaceuticals that act closest to the observed end point. The potential for selectivity is even greater when varying cofactors/pharmaceuticals in conjunction with a select class of antagonists. PMID:29593646

Questioning the social intelligence hypothesis.

PubMed

Holekamp, Kay E

2007-02-01

The social intelligence hypothesis posits that complex cognition and enlarged "executive brains" evolved in response to challenges that are associated with social complexity. This hypothesis has been well supported, but some recent data are inconsistent with its predictions. It is becoming increasingly clear that multiple selective agents, and non-selective constraints, must have acted to shape cognitive abilities in humans and other animals. The task now is to develop a larger theoretical framework that takes into account both inter-specific differences and similarities in cognition. This new framework should facilitate consideration of how selection pressures that are associated with sociality interact with those that are imposed by non-social forms of environmental complexity, and how both types of functional demands interact with phylogenetic and developmental constraints.

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.

[Analysis of cis-regulatory element distribution in gene promoters of Gossypium raimondii and Arabidopsis thaliana].

PubMed

Sun, Gao-Fei; He, Shou-Pu; Du, Xiong-Ming

2013-10-01

Cotton genomic studies have boomed since the release of Gossypium raimondii draft genome. In this study, cis-regulatory element (CRE) in 1 kb length sequence upstream 5' UTR of annotated genes were selected and scanned in the Arabidopsis thaliana (At) and Gossypium raimondii (Gr) genomes, based on the database of PLACE (Plant cis-acting Regulatory DNA Elements). According to the definition of this study, 44 (12.3%) and 57 (15.5%) CREs presented "peak-like" distribution in the 1 kb selected sequences of both genomes, respectively. Thirty-four of them were peak-like distributed in both genomes, which could be further categorized into 4 types based on their core sequences. The coincidence of TATABOX peak position and their actual position ((-) -30 bp) indicated that the position of a common CRE was conservative in different genes, which suggested that the peak position of these CREs was their possible actual position of transcription factors. The position of a common CRE was also different between the two genomes due to stronger length variation of 5' UTR in Gr than At. Furthermore, most of the peak-like CREs were located in the region of -110 bp-0 bp, which suggested that concentrated distribution might be conductive to the interaction of transcription factors, and then regulate the gene expression in downstream.

75 FR 44724 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Reorganization of the Select Agent and Toxin List AGENCY: Animal and Plant Health Inspection Service, USDA... Agricultural Bioterrorism Protection Act of 2002, we are soliciting public comment regarding the list of select...

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

PubMed

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

2017-05-31

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

Heritability, covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment.

PubMed

Johnson, M T J; Agrawal, A A; Maron, J L; Salminen, J-P

2009-06-01

This study explored genetic variation and co-variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life-history traits and secondary chemistry together explained a large proportion of variation in herbivory (r(2) = 0.73). At the same time, selection acted on lifetime biomass, life-history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant-herbivore interactions.

Sexual selection gradients change over time in a simultaneous hermaphrodite

PubMed Central

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

2017-01-01

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

Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract.

PubMed

Li, Jinxing; Thamphiwatana, Soracha; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Angsantikul, Pavimol; Sandraz, Elodie; Wang, Jianxing; Xu, Tailin; Soto, Fernando; Ramez, Valentin; Wang, Xiaolei; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

2016-09-22

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.

PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches

PubMed Central

Fujibuchi, Wataru; Anderson, John S. J.; Landsman, David

2001-01-01

Consensus pattern and matrix-based searches designed to predict cis-acting transcriptional regulatory sequences have historically been subject to large numbers of false positives. We sought to decrease false positives by incorporating expression profile data into a consensus pattern-based search method. We have systematically analyzed the expression phenotypes of over 6000 yeast genes, across 121 expression profile experiments, and correlated them with the distribution of 14 known regulatory elements over sequences upstream of the genes. Our method is based on a metric we term probabilistic element assessment (PEA), which is a ranking of potential sites based on sequence similarity in the upstream regions of genes with similar expression phenotypes. For eight of the 14 known elements that we examined, our method had a much higher selectivity than a naïve consensus pattern search. Based on our analysis, we have developed a web-based tool called PROSPECT, which allows consensus pattern-based searching of gene clusters obtained from microarray data. PMID:11574681

Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine, an allosteric modulator of the serotonin transporter.

PubMed

Boos, Terrence L; Greiner, Elisabeth; Calhoun, W Jason; Prisinzano, Thomas E; Nightingale, Barbara; Dersch, Christina M; Rothman, Richard B; Jacobson, Arthur E; Rice, Kenner C

2006-06-01

A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl) piperidines with substituents at the ortho and meta positions in the aromatic ring of the N-benzyl side chain were synthesized and their affinities and selectivities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined. One analogue, 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine (the C(2)-trifluoromethyl substituted compound), has been found to act as an allosteric modulator of hSERT binding and function. It had little affinity for any of the transporters. Several compounds showed affinity for the DAT in the low nanomolar range and displayed a broad range of SERT/DAT selectivity ratios and very little affinity for the NET. The pharmacological tools provided by the availability of compounds with varying transporter affinity and selectivity could be used to obtain additional information about the properties a compound should have to act as a useful pharmacotherapeutic agent for cocaine addiction and help unravel the pharmacological mechanisms relevant to stimulant abuse.

δ-Conotoxins synthesized using an acid-cleavable solubility tag approach reveal key structural determinants for NaV subtype selectivity.

PubMed

Peigneur, Steve; Paolini-Bertrand, Marianne; Gaertner, Hubert; Biass, Daniel; Violette, Aude; Stöcklin, Reto; Favreau, Philippe; Tytgat, Jan; Hartley, Oliver

2014-12-19

Conotoxins are venom peptides from cone snails with multiple disulfide bridges that provide a rigid structural scaffold. Typically acting on ion channels implicated in neurotransmission, conotoxins are of interest both as tools for pharmacological studies and as potential new medicines. δ-Conotoxins act by inhibiting inactivation of voltage-gated sodium channels (Nav). Their pharmacology has not been extensively studied because their highly hydrophobic character makes them difficult targets for chemical synthesis. Here we adopted an acid-cleavable solubility tag strategy that facilitated synthesis, purification, and directed disulfide bridge formation. Using this approach we readily produced three native δ-conotoxins from Conus consors plus two rationally designed hybrid peptides. We observed striking differences in Nav subtype selectivity across this group of compounds, which differ in primary structure at only three positions: 12, 23, and 25. Our results provide new insights into the structure-activity relationships underlying the Nav subtype selectivity of δ-conotoxins. Use of the acid-cleavable solubility tag strategy should facilitate synthesis of other hydrophobic peptides with complex disulfide bridge patterns. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Simply Imagining Sunshine, Lollipops and Rainbows Will Not Budge the Bias: The Role of Ambiguity in Interpretive Bias Modification.

PubMed

Clarke, Patrick J F; Nanthakumar, Shenooka; Notebaert, Lies; Holmes, Emily A; Blackwell, Simon E; Macleod, Colin

2014-01-01

Imagery-based interpretive bias modification (CBM-I) involves repeatedly imagining scenarios that are initially ambiguous before being resolved as either positive or negative in the last word/s. While the presence of such ambiguity is assumed to be important to achieve change in selective interpretation, it is also possible that the act of repeatedly imagining positive or negative events could produce such change in the absence of ambiguity. The present study sought to examine whether the ambiguity in imagery-based CBM-I is necessary to elicit change in interpretive bias, or, if the emotional content of the imagined scenarios is sufficient to produce such change. An imagery-based CBM-I task was delivered to participants in one of four conditions, where the valence of imagined scenarios were either positive or negative, and the ambiguity of the scenario was either present (until the last word/s) or the ambiguity was absent (emotional valence was evident from the start). Results indicate that only those who received scenarios in which the ambiguity was present acquired an interpretive bias consistent with the emotional valence of the scenarios, suggesting that the act of imagining positive or negative events will only influence patterns of interpretation when the emotional ambiguity is a consistent feature.

Gene expression divergence between malaria vector sibling species Anopheles gambiae and An. coluzzii from rural and urban Yaoundé Cameroon

PubMed Central

Cassone, Bryan J.; Kamdem, Colince; Cheng, Changde; Tan, John C.; Hahn, Matthew W.; Costantini, Carlo; Besansky, Nora J.

2014-01-01

Divergent selection based on aquatic larval ecology is a likely factor in the recent isolation of two broadly sympatric and morphologically identical African mosquito species, the malaria vectors Anopheles gambiae and An. coluzzii. Population-based genome scans have revealed numerous candidate regions of recent positive selection, but have provided few clues as to the genetic mechanisms underlying behavioral and physiological divergence between the two species, phenotypes which themselves remain obscure. To uncover possible genetic mechanisms, we compared global transcriptional profiles of natural and experimental populations using gene-based microarrays. Larvae were sampled as second and fourth instars from natural populations in and around the city of Yaoundé, capital of Cameroon, where the two species segregate along a gradient of urbanization. Functional enrichment analysis of differentially expressed genes revealed that An. coluzzii—the species that breeds in more stable, biotically complex and potentially polluted urban water bodies—over-expresses genes implicated in detoxification and immunity relative to An. gambiae, which breeds in more ephemeral and relatively depauperate pools and puddles in suburbs and rural areas. Moreover, our data suggest that such over-expression by An. coluzzii is not a transient result of induction by xenobiotics in the larval habitat, but an inherent and presumably adaptive response to repeatedly encountered environmental stressors. Finally, we find no significant overlap between the differentially expressed loci and previously identified genomic regions of recent positive selection, suggesting that transcriptome divergence is regulated by trans-acting factors rather than cis-acting elements. PMID:24673723

Strong Purifying Selection at Synonymous Sites in D. melanogaster

PubMed Central

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

2013-01-01

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

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.

Recombination and positive selection contributed to the evolution of Listeria monocytogenes lineages III and IV, two distinct and well supported uncommon L. monocytogenes lineages.

PubMed

Tsai, Yeu-Harn Lucy; Maron, Steve B; McGann, Patrick; Nightingale, Kendra K; Wiedmann, Martin; Orsi, Renato H

2011-12-01

Listeriamonocytogenes lineages III and IV represent two uncommon lineages of the human and animal pathogen L. monocytogenes, characterized by occurrence of unusual phenotypic and genetic characteristics that differentiate them from the common lineages I and II. To gain further insights into the evolution of lineages III and IV, we amplified and sequenced housekeeping genes (i.e., gap, prs, purM, ribC, and sigB), internalin genes (i.e., inlA, inlB, inlC, inlG, inlC2, inlD, inlE, inlF, and inlH) and the virulence gene cluster containing prfA, plcA, hly, mpl, actA, and plcB for lineages III (n = 7) and IV (n = 4) isolates. Phylogenetic analyses of the sequences obtained along with previously reported sequence data for 40 isolates representing lineages I (n = 18), II (n = 21), and III (n = 1), showed that lineages III and IV represent divergent and monophyletic lineages. The virulence gene cluster as well as the inlAB operon were present in all isolates, with inlF absent from all lineages III and IV isolates. While all lineage IV isolates contained only inlC (in addition to inlAB), lineage III isolates showed considerable diversity with regard to internalin gene presence, including presence of (i) only inlC (n = 2), (ii) inlC and inlGC2DE (n = 3), (iii) only inlGC2DE (n = 2), and (iv) inlC and inlC2DE (n = 1). In addition to evidence for horizontal gene transfer events, among lineages III and IV isolates, in prs, actA, plcB, mpl, inlA, inlB, inlG, inlD, and inlE, we also found significant evidence for positive selection in the hly promoter region and, along the lineages III and IV branches, for actA (including in sites recognized for interactions with proteins involved in actin tail polymerization). In conclusion, lineages III and IV represent two distinct monophyletic groups with contributions of intragenic recombination to the evolution of their internalin genes as well as contributions of positive selection to evolution of the virulence genes island. Copyright © 2011 Elsevier B.V. All rights reserved.

Tunnel effect measuring systems and particle detectors

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1994-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Tunnel effect measuring systems and particle detectors

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1993-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Tunnel effect wave energy detection

NASA Technical Reports Server (NTRS)

Kaiser, William J. (Inventor); Waltman, Steven B. (Inventor); Kenny, Thomas W. (Inventor)

1995-01-01

Methods and apparatus for measuring gravitational and inertial forces, magnetic fields, or wave or radiant energy acting on an object or fluid in space provide an electric tunneling current through a gap between an electrode and that object or fluid in space and vary that gap with any selected one of such forces, magnetic fields, or wave or radiant energy acting on that object or fluid. These methods and apparatus sense a corresponding variation in an electric property of that gap and determine the latter force, magnetic fields, or wave or radiant energy in response to that corresponding variation, and thereby sense or measure such parameters as acceleration, position, particle mass, velocity, magnetic field strength, presence or direction, or wave or radiant energy intensity, presence or direction.

Male reproductive fitness and queen polyandry are linked to variation in the supergene Gp-9 in the fire ant Solenopsis invicta.

PubMed

Lawson, Lucinda P; Vander Meer, Robert K; Shoemaker, Dewayne

2012-08-22

Supergenes are clusters of tightly linked loci maintained in specific allelic combinations to facilitate co-segregation of genes governing adaptive phenotypes. In species where strong selection potentially operates at different levels (e.g. eusocial Hymenoptera), positive selection acting within a population to maintain specific allelic combinations in supergenes may have unexpected consequences for some individuals, including the preservation of disadvantageous traits. The nuclear gene Gp-9 in the invasive fire ant Solenopsis invicta is part of a non-recombining, polymorphic supergene region associated with polymorphism in social organization as well as traits affecting physiology, fecundity and behaviour. We show that both male reproductive success and facultative polyandry in queens have a simple genetic basis and are dependent on male Gp-9 genotype. Gp-9(b) males are unable to maintain exclusive reproductive control over their mates such that queens mated to Gp-9(b) males remain highly receptive to remating. Queens mated to multiple Gp-9(B) males are rare. This difference appears to be independent of mating plug production in fertile males of each Gp-9 genotype. However, Gp-9(b) males have significantly lower sperm counts than Gp-9(B) males, which could be a cue to females to seek additional mates. Despite the reduced fitness of Gp-9(b) males, polygyne worker-induced selective mortality of sexuals lacking b-like alleles coupled with the overall success of the polygyne social form act to maintain the Gp-9(b) allele within nature. Our findings highlight how strong worker-induced selection acting to maintain the Gp-9(b) allele in the polygyne social form may simultaneously result in reduced reproductive fitness for individual sexual offspring.

Male reproductive fitness and queen polyandry are linked to variation in the supergene Gp-9 in the fire ant Solenopsis invicta

PubMed Central

Lawson, Lucinda P.; Vander Meer, Robert K.; Shoemaker, DeWayne

2012-01-01

Supergenes are clusters of tightly linked loci maintained in specific allelic combinations to facilitate co-segregation of genes governing adaptive phenotypes. In species where strong selection potentially operates at different levels (e.g. eusocial Hymenoptera), positive selection acting within a population to maintain specific allelic combinations in supergenes may have unexpected consequences for some individuals, including the preservation of disadvantageous traits. The nuclear gene Gp-9 in the invasive fire ant Solenopsis invicta is part of a non-recombining, polymorphic supergene region associated with polymorphism in social organization as well as traits affecting physiology, fecundity and behaviour. We show that both male reproductive success and facultative polyandry in queens have a simple genetic basis and are dependent on male Gp-9 genotype. Gp-9b males are unable to maintain exclusive reproductive control over their mates such that queens mated to Gp-9b males remain highly receptive to remating. Queens mated to multiple Gp-9B males are rare. This difference appears to be independent of mating plug production in fertile males of each Gp-9 genotype. However, Gp-9b males have significantly lower sperm counts than Gp-9B males, which could be a cue to females to seek additional mates. Despite the reduced fitness of Gp-9b males, polygyne worker-induced selective mortality of sexuals lacking b-like alleles coupled with the overall success of the polygyne social form act to maintain the Gp-9b allele within nature. Our findings highlight how strong worker-induced selection acting to maintain the Gp-9b allele in the polygyne social form may simultaneously result in reduced reproductive fitness for individual sexual offspring. PMID:22535783

Evolution and inheritance of early embryonic patterning in Drosophila simulans and D. sechellia.

PubMed

Lott, Susan E; Ludwig, Michael Z; Kreitman, Martin

2011-05-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation that selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth "stripe allometry") in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species Drosophila simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the "margin of error" for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Adaptive Evolution of the Insulin Two-Gene System in Mouse

PubMed Central

Shiao, Meng-Shin; Liao, Ben-Yang; Long, Manyuan; Yu, Hon-Tsen

2008-01-01

Insulin genes in mouse and rat compose a two-gene system in which Ins1 was retroposed from the partially processed mRNA of Ins2. When Ins1 originated and how it was retained in genomes still remain interesting problems. In this study, we used genomic approaches to detect insulin gene copy number variation in rodent species and investigated evolutionary forces acting on both Ins1 and Ins2. We characterized the phylogenetic distribution of the new insulin gene (Ins1) by Southern analyses and confirmed by sequencing insulin genes in the rodent genomes. The results demonstrate that Ins1 originated right before the mouse–rat split (∼20 MYA), and both Ins1 and Ins2 are under strong functional constraints in these murine species. Interestingly, by examining a range of nucleotide polymorphisms, we detected positive selection acting on both Ins2 and Ins1 gene regions in the Mus musculus domesticus populations. Furthermore, three amino acid sites were also identified as having evolved under positive selection in two insulin peptides: two are in the signal peptide and one is in the C-peptide. Our data suggest an adaptive divergence in the mouse insulin two-gene system, which may result from the response to environmental change caused by the rise of agricultural civilization, as proposed by the thrifty-genotype hypothesis. PMID:18245324

Positive mood broadens visual attention to positive stimuli.

PubMed

Wadlinger, Heather A; Isaacowitz, Derek M

2006-03-01

In an attempt to investigate the impact of positive emotions on visual attention within the context of Fredrickson's (1998) broaden-and-build model, eye tracking was used in two studies to measure visual attentional preferences of college students (n=58, n=26) to emotional pictures. Half of each sample experienced induced positive mood immediately before viewing slides of three similarly-valenced images, in varying central-peripheral arrays. Attentional breadth was determined by measuring the percentage viewing time to peripheral images as well as by the number of visual saccades participants made per slide. Consistent with Fredrickson's theory, the first study showed that individuals induced into positive mood fixated more on peripheral stimuli than did control participants; however, this only held true for highly-valenced positive stimuli. Participants under induced positive mood also made more frequent saccades for slides of neutral and positive valence. A second study showed that these effects were not simply due to differences in emotional arousal between stimuli. Selective attentional broadening to positive stimuli may act both to facilitate later building of resources as well as to maintain current positive affective states.

A new look at the Dynamic Similarity Hypothesis: the importance of swing phase.

PubMed

Raichlen, David A; Pontzer, Herman; Shapiro, Liza J

2013-01-01

The Dynamic Similarity Hypothesis (DSH) suggests that when animals of different size walk at similar Froude numbers (equal ratios of inertial and gravitational forces) they will use similar size-corrected gaits. This application of similarity theory to animal biomechanics has contributed to fundamental insights in the mechanics and evolution of a diverse set of locomotor systems. However, despite its popularity, many mammals fail to walk with dynamically similar stride lengths, a key element of gait that determines spontaneous speed and energy costs. Here, we show that the applicability of the DSH is dependent on the inertial forces examined. In general, the inertial forces are thought to be the centripetal force of the inverted pendulum model of stance phase, determined by the length of the limb. If instead we model inertial forces as the centripetal force of the limb acting as a suspended pendulum during swing phase (determined by limb center of mass position), the DSH for stride length variation is fully supported. Thus, the DSH shows that inter-specific differences in spatial kinematics are tied to the evolution of limb mass distribution patterns. Selection may act on morphology to produce a given stride length, or alternatively, stride length may be a "spandrel" of selection acting on limb mass distribution.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-08-01

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

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

PubMed

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

2012-07-01

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

20 CFR 670.420 - Are there any special requirements for enrollment related to the Military Selective Service Act?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Are there any special requirements for enrollment related to the Military Selective Service Act? 670.420 Section 670.420 Employees' Benefits... INVESTMENT ACT Recruitment, Eligibility, Screening, Selection and Assignment, and Enrollment § 670.420 Are...

75 FR 42363 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and... Act) requires the biennial review and republication of the HHS list of select agents and toxins. Accordingly, we are soliciting public comment on the current HHS list of select agents and toxins, including...

Survey of restaurants regarding smoking policies.

PubMed

Williams, Alcia; Peterson, Elizabeth; Knight, Susan; Hiller, Marc; Pelletier, Andrew

2004-01-01

The New Hampshire Indoor Smoking Act was implemented in 1994 to protect the public's health by regulating smoking in enclosed places. A survey was conducted of New Hampshire restaurants to determine smoking policies, to determine restaurant characteristics associated with smoking policies, and to evaluate compliance with the Indoor Smoking Act. A list of New Hampshire restaurants was obtained from a marketing firm. Establishments were selected randomly until 400 had completed a 22-question telephone survey. Forty-four percent of restaurants permitted smoking. Characteristics positively associated with permitting smoking were being a non-fast-food restaurant, selling alcohol, selling tobacco, and having greater than the median number of seats. Of restaurants permitting smoking, 96.1% had a designated smoking area, 87.0% had a ventilation system to minimize secondhand smoke, 83.6% had a physical barrier between smoking and nonsmoking areas, and 53.1% exhibited signs marking the smoking area. Forty percent of restaurants permitting smoking met all four requirements of the Indoor Smoking Act. Smoking policies differ, by type of restaurant. Compliance with the Indoor Smoking Act is low.

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

PubMed

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

2017-09-01

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

Neuroglian-positive plasmatocytes of Manduca sexta and the initiation of hemocyte attachment to foreign surfaces.

PubMed

Nardi, James B; Pilas, Barbara; Bee, Charles Mark; Zhuang, Shufei; Garsha, Karl; Kanost, Michael R

2006-01-01

Observations of hemocyte aggregation on abiotic surfaces suggested that certain plasmatocytes from larvae of Manduca sexta act as foci for hemocyte aggregation. To establish how these particular plasmatocytes form initial attachments to foreign surfaces, they were cultured separately from other selected populations of hemocytes. While all circulating plasmatocytes immunolabel with anti-beta-integrin monoclonal antibody (MAb), only these larger plasmatocytes immunolabel with a MAb to the adhesion protein neuroglian. Neuroglian-negative plasmatocytes and granular cells that have been magnetically segregated from the majority of granular cells adhere to each other but fail to adhere to foreign substrata; by contrast, neuroglian-positive plasmatocytes that segregate with most granular cells adhere firmly to a substratum. Hemocytes form stable aggregates around the large, neuroglian-positive plasmatocytes. However, if neuroglian-positive plasmatocytes are separated from most granular cells, attachment of these plasmatocytes to foreign surfaces is suppressed.

A satellite digital controller or 'play that PID tune again, Sam'. [Position, Integral, Derivative feedback control algorithm for design strategy

NASA Technical Reports Server (NTRS)

Seltzer, S. M.

1976-01-01

The problem discussed is to design a digital controller for a typical satellite. The controlled plant is considered to be a rigid body acting in a plane. The controller is assumed to be a digital computer which, when combined with the proposed control algorithm, can be represented as a sampled-data system. The objective is to present a design strategy and technique for selecting numerical values for the control gains (assuming position, integral, and derivative feedback) and the sample rate. The technique is based on the parameter plane method and requires that the system be amenable to z-transform analysis.

Analysis of Major Genome Loci Underlying Artemisinin Resistance and pfmdr1 Copy Number in pre- and post-ACTs in Western Kenya

PubMed Central

Ngalah, Bidii S.; Ingasia, Luiser A.; Cheruiyot, Agnes C.; Chebon, Lorna J.; Juma, Dennis W.; Muiruri, Peninah; Onyango, Irene; Ogony, Jack; Yeda, Redemptah A.; Cheruiyot, Jelagat; Mbuba, Emmanuel; Mwangoka, Grace; Achieng, Angela O.; Ng'ang'a, Zipporah; Andagalu, Ben; Akala, Hoseah M.; Kamau, Edwin

2015-01-01

Genetic analysis of molecular markers is critical in tracking the emergence and/or spread of artemisinin resistant parasites. Clinical isolates collected in western Kenya pre- and post- introduction of artemisinin combination therapies (ACTs) were genotyped at SNP positions in regions of strong selection signatures on chromosome 13 and 14, as described in Southeast Asia (SEA). Twenty five SNPs were genotyped using Sequenom MassArray and pfmdr1 gene copy number by real-time PCR. Parasite clearance half-life and in vitro drug sensitivity testing were performed using standard methods. One hundred twenty nine isolates were successfully analyzed. Fifteen SNPs were present in pre-ACTs isolates and six in post-ACTs. None of the SNPs showed association with parasite clearance half-life. Post-ACTs parasites had significantly higher pfmdr1 copy number compared to pre-ACTs. Seven of eight parasites with multiple pfmdr1 were post-ACTs. When in vitro IC50s were compared for parasites with single vs. multiple gene copies, only amodiaquine and piperaquine reached statistical significance. Data showed SNPs on chromosome 13 and 14 had different frequency and trend in western Kenya parasites compared SEA. Increase in pfmdr1 gene copy is consistent with recent studies in African parasites. Data suggests genetic signature of artemisinin resistance in Africa might be different from SEA. PMID:25655315

Political Culture and the Nature of Political Participation in Egypt.

DTIC Science & Technology

1980-06-01

the committee which included Muhyi al -Din, Sabri, Abd al -Latif al - Baghdadi and Sami Sharaf. Sadat’s first act independent of the committee was his order...military officers, including Baghdadi and Air Force General Madkuri al -Izz, demands were made for Sadat to restore Egypt’s position between the...published in Al -Tali’a, Al -Ahram, and Eyptian Gazette, May-June, 1972. English translations of selected excerpts are contained in FBIS and JPRS. 89

Adaptive evolution of the Hox gene family for development in bats and dolphins.

PubMed

Liang, Lu; Shen, Yong-Yi; Pan, Xiao-Wei; Zhou, Tai-Cheng; Yang, Chao; Irwin, David M; Zhang, Ya-Ping

2013-01-01

Bats and cetaceans (i.e., whales, dolphins, porpoises) are two kinds of mammals with unique locomotive styles and occupy novel niches. Bats are the only mammals capable of sustained flight in the sky, while cetaceans have returned to the aquatic environment and are specialized for swimming. Associated with these novel adaptations to their environment, various development changes have occurred to their body plans and associated structures. Given the importance of Hox genes in many aspects of embryonic development, we conducted an analysis of the coding regions of all Hox gene family members from bats (represented by Pteropus vampyrus, Pteropus alecto, Myotis lucifugus and Myotis davidii) and cetaceans (represented by Tursiops truncatus) for adaptive evolution using the available draft genome sequences. Differences in the selective pressures acting on many Hox genes in bats and cetaceans were found compared to other mammals. Positive selection, however, was not found to act on any of the Hox genes in the common ancestor of bats and only upon Hoxb9 in cetaceans. PCR amplification data from additional bat and cetacean species, and application of the branch-site test 2, showed that the Hoxb2 gene within bats had significant evidence of positive selection. Thus, our study, with genomic and newly sequenced Hox genes, identifies two candidate Hox genes that may be closely linked with developmental changes in bats and cetaceans, such as those associated with the pancreatic, neuronal, thymus shape and forelimb. In addition, the difference in our results from the genome-wide scan and newly sequenced data reveals that great care must be taken in interpreting results from draft genome data from a limited number of species, and deep genetic sampling of a particular clade is a powerful tool for generating complementary data to address this limitation.

Adaptive Evolution of the Hox Gene Family for Development in Bats and Dolphins

PubMed Central

Pan, Xiao-Wei; Zhou, Tai-Cheng; Yang, Chao; Irwin, David M.; Zhang, Ya-Ping

2013-01-01

Bats and cetaceans (i.e., whales, dolphins, porpoises) are two kinds of mammals with unique locomotive styles and occupy novel niches. Bats are the only mammals capable of sustained flight in the sky, while cetaceans have returned to the aquatic environment and are specialized for swimming. Associated with these novel adaptations to their environment, various development changes have occurred to their body plans and associated structures. Given the importance of Hox genes in many aspects of embryonic development, we conducted an analysis of the coding regions of all Hox gene family members from bats (represented by Pteropus vampyrus, Pteropus alecto, Myotis lucifugus and Myotis davidii) and cetaceans (represented by Tursiops truncatus) for adaptive evolution using the available draft genome sequences. Differences in the selective pressures acting on many Hox genes in bats and cetaceans were found compared to other mammals. Positive selection, however, was not found to act on any of the Hox genes in the common ancestor of bats and only upon Hoxb9 in cetaceans. PCR amplification data from additional bat and cetacean species, and application of the branch-site test 2, showed that the Hoxb2 gene within bats had significant evidence of positive selection. Thus, our study, with genomic and newly sequenced Hox genes, identifies two candidate Hox genes that may be closely linked with developmental changes in bats and cetaceans, such as those associated with the pancreatic, neuronal, thymus shape and forelimb. In addition, the difference in our results from the genome-wide scan and newly sequenced data reveals that great care must be taken in interpreting results from draft genome data from a limited number of species, and deep genetic sampling of a particular clade is a powerful tool for generating complementary data to address this limitation. PMID:23825528

76 FR 26948 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

...] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S... series of public meetings on the implementation of provisions of the Small Business Jobs Act of 2010... INFORMATION CONTACT: Richard L. Miller, Small Business Job's Act Tour-Office of Government Contracting and...

Metabolic effects of exercise on childhood obesity: a current view

PubMed Central

Paes, Santiago Tavares; Marins, João Carlos Bouzas; Andreazzi, Ana Eliza

2015-01-01

OBJECTIVE: To review the current literature concerning the effects of physical exercise on several metabolic variables related to childhood obesity. DATA SOURCE: A search was performed in Pubmed/MEDLINE and Web of Science databases. The keywords used were as follows: Obesity, Children Obesity, Childhood Obesity, Exercise and Physical Activity. The online search was based on studies published in English, from April 2010 to December 2013. DATA SYNTHESIS: Search queries returned 88,393 studies based on the aforementioned keywords; 4,561 studies were selected by crossing chosen keywords. After applying inclusion criteria, four studies were selected from 182 eligible titles. Most studies found that aerobic and resistance training improves body composition, lipid profile and metabolic and inflammatory status of obese children and adolescents; however, the magnitude of these effects is associated with the type, intensity and duration of practice. CONCLUSIONS: Regardless of the type, physical exercise promotes positive adaptations to childhood obesity, mainly acting to restore cellular and cardiovascular homeostasis, to improve body composition, and to activate metabolism; therefore, physical exercise acts as a co-factor in fighting obesity. PMID:25662015

Explaining negative kin discrimination in a cooperative mammal society

PubMed Central

Cant, Michael A.; Sanderson, Jennifer L.; Gilchrist, Jason S.; Bell, Matthew B. V.; Hodge, Sarah J.; Johnstone, Rufus A.

2017-01-01

Kin selection theory predicts that, where kin discrimination is possible, animals should typically act more favorably toward closer genetic relatives and direct aggression toward less closely related individuals. Contrary to this prediction, we present data from an 18-y study of wild banded mongooses, Mungos mungo, showing that females that are more closely related to dominant individuals are specifically targeted for forcible eviction from the group, often suffering severe injury, and sometimes death, as a result. This pattern cannot be explained by inbreeding avoidance or as a response to more intense local competition among kin. Instead, we use game theory to show that such negative kin discrimination can be explained by selection for unrelated targets to invest more effort in resisting eviction. Consistent with our model, negative kin discrimination is restricted to eviction attempts of older females capable of resistance; dominants exhibit no kin discrimination when attempting to evict younger females, nor do they discriminate between more closely or less closely related young when carrying out infanticidal attacks on vulnerable infants who cannot defend themselves. We suggest that in contexts where recipients of selfish acts are capable of resistance, the usual prediction of positive kin discrimination can be reversed. Kin selection theory, as an explanation for social behavior, can benefit from much greater exploration of sequential social interactions. PMID:28439031

Epidemiological and genetic analysis concerning the non-enterovirus 71 and non-coxsackievirus A16 causative agents related to hand, foot and mouth disease in Anyang city, Henan Province, China, from 2011 to 2015.

PubMed

Li, Yang; Bao, Honghong; Zhang, Xiangping; Zhai, Mingqiang; Bao, Xiaobing; Wang, Demin; Zhang, Shuanhu

2017-10-01

Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are major pathogens of hand, foot, and mouth disease (HFMD) and have been associated with consecutive outbreaks of HFMD in China over the past years. Although several other human enteroviruses (HEVs) have also acted as causative agents of HFMD, published information on their roles in the prevalence of HFMD is limited. This study was conducted to reveal the characteristics of the pathogenic spectrum and molecular epidemiology of the non-EV-71 and -CV-A16 HEVs in Anyang City, which is located in north-central China and has a population of five million. From 2011 to 2015, 2270 samples were collected from HFMD patients (3.89 ± 1.06 years of age), and 1863 HEV-positive samples, including 524 samples with 23 non-EV-71 and non-CV-A16 serotypes, were identified. Based on the nucleotide sequence of the VP1 gene, 6 common non-EV-71 and non-CV-A16 HEVs, including coxsackievirus A2, A6, A10, A14, B2, and B5, were studied to determine their phylogenies and selective pressures. Phylogenetic analyses revealed a high level of genetic divergence and a pattern of lineage replacement over time in Mainland China. Selective pressure analyses showed that purifying selection was predominant in the evolution of the VP1 gene, whereas positive selection acted on individual codons. Overall, non-EV-71 and non-CV-A16 HEVs were important constituents of the pathogenic spectrum of HFMD in Anyang City during 2011-2015. Some of these HEVs with complex and active phylogenies represent a potential threat to public health, suggesting that long-term monitoring of these pathogens should be implemented to prevent HFMD outbreaks. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2010-03-01

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

Deconstructing Ras Signaling in the Thymus

PubMed Central

Kortum, Robert L.; Sommers, Connie L.; Pinski, John M.; Alexander, Clayton P.; Merrill, Robert K.; Li, Wenmei; Love, Paul E.

2012-01-01

Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1 deletion was required to block negative selection. This functional redundancy in RasGEFs during negative selection may act as a failsafe mechanism ensuring appropriate central tolerance. PMID:22586275

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants.

PubMed

Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W

2012-07-26

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.

Evidence for positive selection and recombination hotspots in Deformed wing virus (DWV).

PubMed

Dalmon, A; Desbiez, C; Coulon, M; Thomasson, M; Le Conte, Y; Alaux, C; Vallon, J; Moury, B

2017-01-25

Deformed wing virus (DWV) is considered one of the most damaging pests in honey bees since the spread of its vector, Varroa destructor. In this study, we sequenced the whole genomes of two virus isolates and studied the evolutionary forces that act on DWV genomes. The isolate from a Varroa-tolerant bee colony was characterized by three recombination breakpoints between DWV and the closely related Varroa destructor virus-1 (VDV-1), whereas the variant from the colony using conventional Varroa management was similar to the originally described DWV. From the complete sequence dataset, nine independent DWV-VDV-1 recombination breakpoints were detected, and recombination hotspots were found in the 5' untranslated region (5' UTR) and the conserved region encoding the helicase. Partial sequencing of the 5' UTR and helicase-encoding region in 41 virus isolates suggested that most of the French isolates were recombinants. By applying different methods based on the ratio between non-synonymous (dN) and synonymous (dS) substitution rates, we identified four positions that showed evidence of positive selection. Three of these positions were in the putative leader protein (Lp), and one was in the polymerase. These findings raise the question of the putative role of the Lp in viral evolution.

The anticonvulsant stiripentol acts directly on the GABAA receptor as a positive allosteric modulator

PubMed Central

Fisher, Janet L.

2009-01-01

SUMMARY Stiripentol(STP) has been used as co-therapy for treatment of epilepsy for many years. Its mechanism of action has long been considered to be indirect, as it inhibits the enzymes responsible for metabolism of other anticonvulsant agents. However, a recent report suggested that STP might also act at the neuronal level, increasing inhibitory GABAergic neurotransmission. We examined the effect of STP on the functional properties of recombinant GABAA receptors (GABARs) and found that it was a positive allosteric modulator of these ion channels. Its activity showed some dependence on subunit composition, with greater potentiation of α3-containing receptors and reduced potentiation when the β1 or ε subunits were present. STP caused a leftward shift in the GABA concentration-response relationship, but did not increase the peak response of the receptors to a maximal GABA concentration. Although STP shares some functional characteristics with the neurosteroids, its activity was not inhibited by a neurosteroid site antagonist and was unaffected by a mutation in the α3 subunit that reduced positive modulation by neurosteroids. The differential effect of STP on β1- and β2/β3-containing receptors was not altered by mutations within the second transmembrane domain that affect modulation by loreclezole. These findings suggest that STP acts as a direct allosteric modulator of the GABAR at a site distinct from many commonly used anti-convulsant, sedative and anxiolytic drugs. Its higher activity at α3-containing receptors as well as its activity at δ-containing receptors may provide a unique opportunity to target selected populations of GABARs. PMID:18585399

29 CFR 825.123 - Unable to perform the functions of the position.

Code of Federal Regulations, 2014 CFR

2014-07-01

... LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.123 Unable to perform the functions of the position. (a) Definition. An employee is unable... position within the meaning of the Americans with Disabilities Act (ADA), as amended, 42 U.S.C. 12101 et...

29 CFR 825.123 - Unable to perform the functions of the position.

Code of Federal Regulations, 2013 CFR

2013-07-01

... LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.123 Unable to perform the functions of the position. (a) Definition. An employee is unable... position within the meaning of the Americans with Disabilities Act (ADA), as amended, 42 U.S.C. 12101 et...

Capsid coding region diversity of re-emerging lineage C foot-and-mouth disease virus serotype Asia1 from India.

PubMed

Subramaniam, Saravanan; Mohapatra, Jajati K; Das, Biswajit; Sharma, Gaurav K; Biswal, Jitendra K; Mahajan, Sonalika; Misri, Jyoti; Dash, Bana B; Pattnaik, Bramhadev

2015-07-01

Foot-and-mouth disease virus (FMDV) serotype Asia1 was first reported in India in 1951, where three major genetic lineages (B, C and D) of this serotype have been described until now. In this study, the capsid protein coding region of serotype Asia1 viruses (n = 99) from India were analyzed, giving importance to the viruses circulating since 2007. All of the isolates (n = 50) recovered during 2007-2013 were found to group within the re-emerging cluster of lineage C (designated as sublineage C(R)). The evolutionary rate of sublineage C(R) was estimated to be slightly higher than that of the serotype as a whole, and the time of the most recent common ancestor for this cluster was estimated to be approximately 2001. In comparison to the older isolates of lineage C (1993-2001), the re-emerging viruses showed variation at eight amino acid positions, including substitutions at the antigenically critical residues VP279 and VP2131. However, no direct correlation was found between sequence variations and antigenic relationships. The number of codons under positive selection and the nature of the selection pressure varied widely among the structural proteins, implying a heterogeneous pattern of evolution in serotype Asia1. While episodic diversifying selection appears to play a major role in shaping the evolution of VP1 and VP3, selection pressure acting on codons of VP2 is largely pervasive. Further, episodic positive selection appears to be responsible for the early diversification of lineage C. Recombination events identified in the structural protein coding region indicates its probable role in adaptive evolution of serotype Asia1 viruses.

29 CFR 825.123 - Unable to perform the functions of the position.

Code of Federal Regulations, 2012 CFR

2012-07-01

... LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.123 Unable to perform the functions of the position. (a) Definition. An employee is “unable... position within the meaning of the Americans with Disabilities Act (ADA), as amended, 42 U.S.C. 12101 et...

29 CFR 825.123 - Unable to perform the functions of the position.

Code of Federal Regulations, 2011 CFR

2011-07-01

... LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.123 Unable to perform the functions of the position. (a) Definition. An employee is “unable... position within the meaning of the Americans with Disabilities Act (ADA), as amended, 42 U.S.C. 12101 et...

"Knowledge Is Acting": Working-Class Parents' Intentional Acts of Positioning within the Discursive Practice of Involvement

ERIC Educational Resources Information Center

Freeman, Melissa

2010-01-01

Positioning theory provides a lens through which to view the narrative accounts of working-class parents as dynamic, intentional acts of positioning intended to gain the recognition of school personnel as full partners in the education of their children. Knowing that school personnel will not treat them with the kind of respect given middle-class…

76 FR 77914 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations AGENCY: Animal and Plant Health Inspection Service, USDA... proposed rule that would amend and republish the list of select agents and toxins that have the potential...

A bambusuril macrocycle that binds anions in water with high affinity and selectivity.

PubMed

Yawer, Mirza Arfan; Havel, Vaclav; Sindelar, Vladimir

2015-01-02

Synthetic receptors that function in water are important for the qualitative and quantitative detection of anions, which may act as pollutants in the environment or play important roles in biological processes. Neutral receptors are particularly appealing because they are often more selective than positively charged receptors; however, their affinity towards anions in pure water is only in range of 1-10(3)  L mol(-1) . The anion-templated synthesis of a water-soluble bambusuril derivative is shown to be an outstanding receptor for various inorganic anions in pure water, with association constants of up to 10(7)  L mol(-1) . Furthermore, the macrocycle discriminates between anions with unprecedented selectivity (up to 500 000-fold). We anticipate that the combination of remarkable affinity and selectivity of this macrocycle will enable the efficient detection and isolation of diverse anions in aqueous solutions, which is not possible with current supramolecular systems. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling linear and cyclic PKS intermediates through atom replacement.

PubMed

Shakya, Gaurav; Rivera, Heriberto; Lee, D John; Jaremko, Matt J; La Clair, James J; Fox, Daniel T; Haushalter, Robert W; Schaub, Andrew J; Bruegger, Joel; Barajas, Jesus F; White, Alexander R; Kaur, Parminder; Gwozdziowski, Emily R; Wong, Fiona; Tsai, Shiou-Chuan; Burkart, Michael D

2014-12-03

The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs.

Circadian rhythm of acute phase proteins under the influence of bright/dim light during the daytime.

PubMed

Kanikowska, Dominika; Hyun, Ki-Ja; Tokura, Hiromi; Azama, Takashi; Nishimura, Shinya

2005-01-01

We investigated the influence of two different light intensities, dim (100 lx) and bright (5000 lx), during the daytime on the circadian rhythms of selected acute phase proteins of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin (ACT), transfferin (TF), alpha2-macroglobulin (alpha2-m), haptoglobin (HP), and ceruloplasmin (CP). Serum samples were collected from 7 healthy volunteers at 4 h intervals during two separate single 24 h spans during which they were exposed to the respective light intensity conditions. A circadian rhythm was detected only in ACT concentration in the bright light condition. The concentration of ACT, a positive acute phase protein (APP), increased (significantly significant differences in the ACT concentration were detected at 14:00 and 22:00 h) and AGP showed a tendency to be higher under the daytime bright compared to dim light conditions. There were no significant differences between the time point means under daytime dim and bright light conditions for alpha2-M, AGP, Tf, Cp, or Hp. The findings suggest that some, but not all, APP may be influenced by the environmental light intensity.

Sun/shade conditions affect recruitment and local adaptation of a columnar cactus in dry forests.

PubMed

Miranda-Jácome, Antonio; Montaña, Carlos; Fornoni, Juan

2013-02-01

Facilitation among plants in water-limited environments (i.e. where evapotranspiration overcomes the availability of water during the growing season) has been considered a local adaptation to water and light conditions. Among cacti, early life-history stages can benefit from the facilitative effects of nurse plants that reduce solar radiation and water stress. However, whether light condition itself acts as an agent of selection through facilitation remains untested. The aim of this study was to determine (1) whether light conditions affect seedling recruitment, (2) whether the positive effect of shade on seedling recruitment is more intense under more stressful conditions and (3) whether shade condition (facilitation) reduces the magnitude of local adaptation on seedling recruitment relative to full sunlight conditions. A reciprocal transplant experiment, coupled with the artificial manipulation of sun/shade conditions, was performed to test for the effects of local adaptation on germination, seedling survival and growth, using two demes of the columnar cactus Pilosocereus leucocephalus, representing different intensities of stressful conditions. Full sunlight conditions reduced recruitment success and supported the expectation of lower recruitment in more stressful environments. Significant local adaptation was mainly detected under full sunlight conditions, indicating that this environmental factor acts as an agent of selection at both sites. The results supported the expectation that the magnitude of local adaptation, driven by the effects of facilitative nurse plants, is less intense under reduced stressful conditions. This study is the first to demonstrate that sun/shade conditions act as a selective agent accounting for local adaptation in water-limited environments, and that facilitation provided by nurse plants in these environments can attenuate the patterns of local adaptation among plants benefiting from the nurse effect.

Sun/shade conditions affect recruitment and local adaptation of a columnar cactus in dry forests

PubMed Central

Miranda-Jácome, Antonio; Montaña, Carlos; Fornoni, Juan

2013-01-01

Background and Aims Facilitation among plants in water-limited environments (i.e. where evapotranspiration overcomes the availability of water during the growing season) has been considered a local adaptation to water and light conditions. Among cacti, early life-history stages can benefit from the facilitative effects of nurse plants that reduce solar radiation and water stress. However, whether light condition itself acts as an agent of selection through facilitation remains untested. The aim of this study was to determine (1) whether light conditions affect seedling recruitment, (2) whether the positive effect of shade on seedling recruitment is more intense under more stressful conditions and (3) whether shade condition (facilitation) reduces the magnitude of local adaptation on seedling recruitment relative to full sunlight conditions. Methods A reciprocal transplant experiment, coupled with the artificial manipulation of sun/shade conditions, was performed to test for the effects of local adaptation on germination, seedling survival and growth, using two demes of the columnar cactus Pilosocereus leucocephalus, representing different intensities of stressful conditions. Key Results Full sunlight conditions reduced recruitment success and supported the expectation of lower recruitment in more stressful environments. Significant local adaptation was mainly detected under full sunlight conditions, indicating that this environmental factor acts as an agent of selection at both sites. Conclusions The results supported the expectation that the magnitude of local adaptation, driven by the effects of facilitative nurse plants, is less intense under reduced stressful conditions. This study is the first to demonstrate that sun/shade conditions act as a selective agent accounting for local adaptation in water-limited environments, and that facilitation provided by nurse plants in these environments can attenuate the patterns of local adaptation among plants benefiting from the nurse effect. PMID:23223204

The impact of feature selection on one and two-class classification performance for plant microRNAs.

PubMed

Khalifa, Waleed; Yousef, Malik; Saçar Demirci, Müşerref Duygu; Allmer, Jens

2016-01-01

MicroRNAs (miRNAs) are short nucleotide sequences that form a typical hairpin structure which is recognized by a complex enzyme machinery. It ultimately leads to the incorporation of 18-24 nt long mature miRNAs into RISC where they act as recognition keys to aid in regulation of target mRNAs. It is involved to determine miRNAs experimentally and, therefore, machine learning is used to complement such endeavors. The success of machine learning mostly depends on proper input data and appropriate features for parameterization of the data. Although, in general, two-class classification (TCC) is used in the field; because negative examples are hard to come by, one-class classification (OCC) has been tried for pre-miRNA detection. Since both positive and negative examples are currently somewhat limited, feature selection can prove to be vital for furthering the field of pre-miRNA detection. In this study, we compare the performance of OCC and TCC using eight feature selection methods and seven different plant species providing positive pre-miRNA examples. Feature selection was very successful for OCC where the best feature selection method achieved an average accuracy of 95.6%, thereby being ∼29% better than the worst method which achieved 66.9% accuracy. While the performance is comparable to TCC, which performs up to 3% better than OCC, TCC is much less affected by feature selection and its largest performance gap is ∼13% which only occurs for two of the feature selection methodologies. We conclude that feature selection is crucially important for OCC and that it can perform on par with TCC given the proper set of features.

Green synthesis of silver nanoparticles using Azadirachta indica leaf extract and its antimicrobial study

NASA Astrophysics Data System (ADS)

Roy, Pragyan; Das, Bhagyalaxmi; Mohanty, Abhipsa; Mohapatra, Sujata

2017-11-01

In this study, green synthesis of silver nanoparticles was done using leaf extracts of Azadirachta indica. The flavonoids and terpenoids present in the extract act as both reducing and capping agent. Microbes ( Escherichia coli and Gram-positive bacteria) were isolated from borewell water using selective media. The silver nanoparticles showed antimicrobial activities against Gram-positive bacteria and E. coli. However the silver nanoparticles were more effective against E. coli as compared to Gram-positive bacteria. Various techniques were used to characterize synthesized silver nanoparticles such as DLS and UV-visible spectrophotometer. The absorbance peak was in the range of 420-450 nm, that varied depending upon the variation in the concentration of neem extract. This is a very rapid and cost-effective method for generation of silver nanoparticle at room temperature, however, its exact dose in water purification has to be determined.

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

10 CFR Appendix A to Subpart A of... - Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141 (42 U.S.C. 2161), Sec. 145 (42 U.S.C. 2165), Sec. 161 (42 U.S.C. 2201) A Appendix A to... to Subpart A of Part 710—Selected Provisions of the Atomic Energy Act of 1954, as Amended, Sec. 141...

The multilevel analysis of surface acting and mental health: A moderation of positive group affective tone

NASA Astrophysics Data System (ADS)

Lee, Meng-Shiu; Huang, Jui-Chan; Wu, Tzu-Jung

2017-06-01

The purpose of this study is to investigate the relationship among surface acting, mental health, and positive group affective tone. According to the prior theory, this study attempts to establish a comprehensive research framework among these variables, and furthermore tests the moderating effect of positive group affective tone. Data were collected from 435 employees in 52 service industrial companies by questionnaire, and this study conducted multilevel analysis. The results showed that surface acting will negatively affect the mental health. In addition, the positive group affective tone have significant moderating effect on the relationship among surface acting and mental health. Finally, this study discusses managerial implications and highlights future research suggestions.

Revisiting the Quinoxalinedione Scaffold in the Construction of New Ligands for the Ionotropic Glutamate Receptors.

PubMed

Demmer, Charles S; Rombach, David; Liu, Na; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart

2017-11-15

More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work, we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity among the AMPA, NMDA, and KA receptors, and to some extent also obtain full receptor subtype selectivity. Highlights of the study of 44 new analogues are compound 2m being a high affinity ligand for native AMPA receptors (IC 50 = 0.48 μM), analogues 2e,f,h,k,v all displayed selectivity for native NMDA receptors, and compounds 2s,t,u are selective ligand for the GluK1 receptor. Most interestingly, compound 2w was shown to be a GluK3-preferring ligand with full selectivity over native AMPA, KA and NMDA receptors.

Expanding access to transplantation with hepatitis C-positive donors: A new perspective on an old issue.

PubMed

Kling, Catherine E; Limaye, Ajit P; Landis, Charles S; Sibulesky, Lena

2017-02-01

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody-positive (HBcAb+) donors into select recipients, in the era of direct-acting antivirals (DAAs), a new focus should be placed on HCV-positive donors. The transmission rate from HCV antibody-positive (HCVAb+) nucleic acid testing negative (HCV NAT-) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post-transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post-transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic variation but weak genetic covariation between pre- and post-copulatory episodes of sexual selection in Drosophila melanogaster.

PubMed

Travers, L M; Garcia-Gonzalez, F; Simmons, L W

2016-08-01

When females mate polyandrously, male reproductive success depends both on the male's ability to attain matings and on his ability to outcompete rival males in the fertilization of ova post-copulation. Increased investment in  ejaculate components may trade off with investment in precopulatory traits due to resource allocation. Alternatively, pre- and post-copulatory traits could be positively related if individuals can afford to invest heavily in traits advantageous at both episodes of selection. There is empirical evidence for both positive and negative associations between pre- and post-copulatory episodes, but little is known about the genetic basis of these correlations. In this study, we measured morphological, chemical and behavioural precopulatory male traits and investigated their relationship with measures of male fitness (male mating success, remating inhibition and offensive sperm competitiveness) across 40 isofemale lines of Drosophila melanogaster. We found significant variation among isofemale lines, indicating a genetic basis for most of the traits investigated. However, we found weak evidence for genetic correlations between precopulatory traits and our indices of male fitness. Moreover, pre- and post-copulatory episodes of selection were uncorrelated, suggesting selection may act independently at the different episodes to maximize male reproductive success. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures.

PubMed

Chouteau, Mathieu; Llaurens, Violaine; Piron-Prunier, Florence; Joron, Mathieu

2017-08-01

Explaining the maintenance of adaptive diversity within populations is a long-standing goal in evolutionary biology, with important implications for conservation, medicine, and agriculture. Adaptation often leads to the fixation of beneficial alleles, and therefore it erodes local diversity so that understanding the coexistence of multiple adaptive phenotypes requires deciphering the ecological mechanisms that determine their respective benefits. Here, we show how antagonistic frequency-dependent selection (FDS), generated by natural and sexual selection acting on the same trait, maintains mimicry polymorphism in the toxic butterfly Heliconius numata Positive FDS imposed by predators on mimetic signals favors the fixation of the most abundant and best-protected wing-pattern morph, thereby limiting polymorphism. However, by using mate-choice experiments, we reveal disassortative mate preferences of the different wing-pattern morphs. The resulting negative FDS on wing-pattern alleles is consistent with the excess of heterozygote genotypes at the supergene locus controlling wing-pattern variation in natural populations of H. numata The combined effect of positive and negative FDS on visual signals is sufficient to maintain a diversity of morphs displaying accurate mimicry with other local prey, although some of the forms only provide moderate protection against predators. Our findings help understand how alternative adaptive phenotypes can be maintained within populations and emphasize the need to investigate interactions between selective pressures in other cases of puzzling adaptive polymorphism.

Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures

PubMed Central

Chouteau, Mathieu; Llaurens, Violaine; Piron-Prunier, Florence; Joron, Mathieu

2017-01-01

Explaining the maintenance of adaptive diversity within populations is a long-standing goal in evolutionary biology, with important implications for conservation, medicine, and agriculture. Adaptation often leads to the fixation of beneficial alleles, and therefore it erodes local diversity so that understanding the coexistence of multiple adaptive phenotypes requires deciphering the ecological mechanisms that determine their respective benefits. Here, we show how antagonistic frequency-dependent selection (FDS), generated by natural and sexual selection acting on the same trait, maintains mimicry polymorphism in the toxic butterfly Heliconius numata. Positive FDS imposed by predators on mimetic signals favors the fixation of the most abundant and best-protected wing-pattern morph, thereby limiting polymorphism. However, by using mate-choice experiments, we reveal disassortative mate preferences of the different wing-pattern morphs. The resulting negative FDS on wing-pattern alleles is consistent with the excess of heterozygote genotypes at the supergene locus controlling wing-pattern variation in natural populations of H. numata. The combined effect of positive and negative FDS on visual signals is sufficient to maintain a diversity of morphs displaying accurate mimicry with other local prey, although some of the forms only provide moderate protection against predators. Our findings help understand how alternative adaptive phenotypes can be maintained within populations and emphasize the need to investigate interactions between selective pressures in other cases of puzzling adaptive polymorphism. PMID:28673971

MULTIPLE SHAFT TOOL HEAD

DOEpatents

Colbert, H.P.

1962-10-23

An improved tool head arrangement is designed for the automatic expanding of a plurality of ferruled tubes simultaneously. A plurality of output shafts of a multiple spindle drill head are driven in unison by a hydraulic motor. A plurality of tube expanders are respectively coupled to the shafts through individual power train arrangements. The axial or thrust force required for the rolling operation is provided by a double acting hydraulic cylinder having a hollow through shaft with the shaft cooperating with an internally rotatable splined shaft slidably coupled to a coupling rigidly attached to the respectlve output shaft of the drill head, thereby transmitting rotary motion and axial thrust simultaneously to the tube expander. A hydraulic power unit supplies power to each of the double acting cylinders through respective two-position, four-way valves, under control of respective solenoids for each of the cylinders. The solenoids are in turn selectively controlled by a tool selection control unit which in turn is controlled by signals received from a programmed, coded tape from a tape reader. The number of expanders that are extended in a rolling operation, which may be up to 42 expanders, is determined by a predetermined program of operations depending upon the arrangement of the ferruled tubes to be expanded in the tube bundle. The tape reader also supplies dimensional information to a machine tool servo control unit for imparting selected, horizontal and/or vertical movement to the tool head assembly. (AEC)

Differences in malaria care seeking and dispensing outcomes for adults and children attending drug vendors in Nasarawa, Nigeria.

PubMed

Liu, Jenny; Isiguzo, Chinwoke; Sieverding, Maia

2015-08-01

To characterise the differences in care seeking behaviour and dispensing outcomes between adults and children purchasing drugs for malaria at retail shops in Nigeria. In Nasarawa State, retail drug shops were enumerated and a subset of those stocking antimalarials were selected as study sites and surveyed. Customers exiting shops after purchasing antimalarial drugs were surveyed and tested with a malaria rapid diagnostic test. Sick adults and caregivers accompanying sick children were eligible, but individuals purchasing drugs for a sick person that was not present were excluded. Multivariate regression analysis was used to identify the correlates of care seeking and the quality of interaction at the shop. Of 737 participants, 80% were adults and 20% were children (under age 18). Caregivers of sick children were more likely to obtain a prescription prior to attending a drug retailer than adults seeking care for themselves and waited a shorter time before seeking care. Caregivers of sick children were also more likely than sick adults to have been asked about symptoms by the retailer, to have been given an examination, and to have purchased an ACT. Fewer than half of respondents had purchased an ACT. Only 14% of adults, but 27% of children were RDT-positive; RDT-positive children were more likely to have had an ACT purchased for them than RDT-positive adults. Children with suspected malaria tend to receive better care at drug retailers than adults. The degree of overtreatment and prevalence of dispensing non-recommended antimalarials emphasise the need for routine diagnosis before treatment to properly treat both malaria and non-malaria illnesses. © 2015 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Differences in malaria care seeking and dispensing outcomes for adults and children attending drug vendors in Nasarawa, Nigeria

PubMed Central

Liu, Jenny; Isiguzo, Chinwoke; Sieverding, Maia

2015-01-01

Objectives To characterise the differences in care seeking behaviour and dispensing outcomes between adults and children purchasing drugs for malaria at retail shops in Nigeria. Methods In Nasarawa State, retail drug shops were enumerated and a subset of those stocking antimalarials were selected as study sites and surveyed. Customers exiting shops after purchasing antimalarial drugs were surveyed and tested with a malaria rapid diagnostic test. Sick adults and caregivers accompanying sick children were eligible, but individuals purchasing drugs for a sick person that was not present were excluded. Multivariate regression analysis was used to identify the correlates of care seeking and the quality of interaction at the shop. Results Of 737 participants, 80% were adults and 20% were children (under age 18). Caregivers of sick children were more likely to obtain a prescription prior to attending a drug retailer than adults seeking care for themselves and waited a shorter time before seeking care. Caregivers of sick children were also more likely than sick adults to have been asked about symptoms by the retailer, to have been given an examination, and to have purchased an ACT. Fewer than half of respondents had purchased an ACT. Only 14% of adults, but 27% of children were RDT-positive; RDT-positive children were more likely to have had an ACT purchased for them than RDT-positive adults. Conclusions Children with suspected malaria tend to receive better care at drug retailers than adults. The degree of overtreatment and prevalence of dispensing non-recommended antimalarials emphasise the need for routine diagnosis before treatment to properly treat both malaria and non-malaria illnesses. PMID:25877471

Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment.

PubMed

Rohwer, V G; Bonier, F; Martin, P R

2015-10-22

Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype-active bird nests-and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits. © 2015 The Author(s).

Conflict between biotic and climatic selective pressures acting on an extended phenotype in a subarctic, but not temperate, environment

PubMed Central

Rohwer, V. G.; Bonier, F.; Martin, P. R.

2015-01-01

Climatic selective pressures are thought to dominate biotic selective pressures at higher latitudes. However, few studies have experimentally tested how these selective pressures differentially act on traits across latitudes because traits can rarely be manipulated independently of the organism in nature. We overcame this challenge by using an extended phenotype—active bird nests—and conducted reciprocal transplant experiments between a subarctic and temperate site, separated by 14° of latitude. At the subarctic site, biotic selective pressures (nest predation) favoured smaller, non-local temperate nests, whereas climatic selective pressures (temperature) favoured larger local nests, particularly at colder temperatures. By contrast, at the temperate site, climatic and biotic selective pressures acted similarly on temperate and subarctic nests. Our results illustrate a functional trade-off in the subarctic between nest morphologies favoured by biotic versus climatic selective pressures, with climate favouring local nest morphologies. At our temperate site, however, allocative trade-offs in the time and effort devoted to nest construction favour smaller, local nests. Our findings illustrate a conflict between biotic and climatic selective pressures at the northern extremes of a species geographical range, and suggest that trade-offs between trait function and trait elaboration act differentially across latitude to create broad geographic variation in traits. PMID:26490789

[Metabolic effects of exercise on childhood obesity: a current view].

PubMed

Paes, Santiago Tavares; Marins, João Carlos Bouzas; Andreazzi, Ana Eliza

2015-01-01

To review the current literature concerning the effects of physical exercise on several metabolic variables related to childhood obesity. A search was performed in Pubmed/Medline and Web of Science databases. The keywords used were as follows: Obesity, Children Obesity, Childhood Obesity, Exercise and Physical Activity. The online search was based on studies published in English, from April 2010 to December 2013. Search queries returned 88,393 studies based on the aforementioned keywords; 4,561 studies were selected by crossing chosen keywords. After applying inclusion criteria, four studies were selected from 182 eligible titles. Most studies have found that aerobic and resistance training improves body composition, lipid profile and metabolic and inflammatory status of obese children and adolescents; however, the magnitude of the effects is associated with the type, intensity and duration of practice. Regardless of type, physical exercise promotes positive adaptations to childhood obesity, mainly acting to restore cellular and cardiovascular homeostasis, to improve body composition, and to activate metabolism; therefore, physical exercise acts as a co-factor in combating obesity. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Differentiated adaptive evolution, episodic relaxation of selective constraints, and pseudogenization of umami and sweet taste genes TAS1Rs in catarrhine primates.

PubMed

Liu, Guangjian; Walter, Lutz; Tang, Suni; Tan, Xinxin; Shi, Fanglei; Pan, Huijuan; Roos, Christian; Liu, Zhijin; Li, Ming

2014-01-01

Umami and sweet tastes are two important basic taste perceptions that allow animals to recognize diets with nutritious carbohydrates and proteins, respectively. Until recently, analyses of umami and sweet taste were performed on various domestic and wild animals. While most of these studies focused on the pseudogenization of taste genes, which occur mostly in carnivores and species with absolute feeding specialization, omnivores and herbivores were more or less neglected. Catarrhine primates are a group of herbivorous animals (feeding mostly on plants) with significant divergence in dietary preference, especially the specialized folivorous Colobinae. Here, we conducted the most comprehensive investigation to date of selection pressure on sweet and umami taste genes (TAS1Rs) in catarrhine primates to test whether specific adaptive evolution occurred during their diversification, in association with particular plant diets. We documented significant relaxation of selective constraints on sweet taste gene TAS1R2 in the ancestral branch of Colobinae, which might correlate with their unique ingestion and digestion of leaves. Additionally, we identified positive selection acting on Cercopithecidae lineages for the umami taste gene TAS1R1, on the Cercopithecinae and extant Colobinae and Hylobatidae lineages for TAS1R2, and on Macaca lineages for TAS1R3. Our research further identified several site mutations in Cercopithecidae, Colobinae and Pygathrix, which were detected by previous studies altering the sensitivity of receptors. The positively selected sites were located mostly on the extra-cellular region of TAS1Rs. Among these positively selected sites, two vital sites for TAS1R1 and four vital sites for TAS1R2 in extra-cellular region were identified as being responsible for the binding of certain sweet and umami taste molecules through molecular modelling and docking. Our results suggest that episodic and differentiated adaptive evolution of TAS1Rs pervasively occurred in catarrhine primates, most concentrated upon the extra-cellular region of TAS1Rs.

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

PubMed

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

2018-05-31

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

The prepared emotional reflex: intentional preparation of automatic approach and avoidance tendencies as a means to regulate emotional responding.

PubMed

Eder, Andreas B; Rothermund, Klaus; Proctor, Robert W

2010-08-01

Advance preparation of action courses toward emotional stimuli is an effective means to regulate impulsive emotional behavior. Our experiment shows that performing intentional acts of approach and avoidance in an evaluation task influences the unintended activation of approach and avoidance tendencies in another task in which stimulus valence is irrelevant. For the evaluation-relevant blocks, participants received either congruent (positive-approach, negative-avoidance) or incongruent (positive-avoidance, negative-approach) mapping instructions. In the evaluation-irrelevant blocks, approach- and avoidance-related lever movements were selected in response to a stimulus feature other than valence (affective Simon task). Response mapping in the evaluation task influenced performance in the evaluation-irrelevant task: An enhanced affective Simon effect was observed with congruent mapping instructions; in contrast, the effect was reversed when the evaluation task required incongruent responses. Thus, action instructions toward affective stimuli received in one task determined affective response tendencies in another task where these instructions were not in effect. These findings suggest that intentionally prepared short-term links between affective valence and motor responses elicit associated responses without a deliberate act of will, operating like a "prepared reflex." Copyright 2010 APA

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated mu opioid receptor (MOR-1) splice variants

PubMed Central

Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R.; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W.

2012-01-01

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogs were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3′ or 4′ position of the phenyl ring and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower delta opioid receptor affinity than its naltrexamine analog, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity. PMID:22734622

Excitation of surface plasmon polaritons by fluorescent light from organic nanofibers

NASA Astrophysics Data System (ADS)

Sobolewska, Elżbieta Karolina; Józefowski, Leszek; Kawalec, Tomasz; Leißner, Till; Rubahn, Horst-Günter; Adam, Jost; Fiutowski, Jacek

2017-11-01

Micro- and nano-scale systems with defined active elements acting as local surface plasmons polariton (SPP) sources are crucial for the development of future plasmonic circuits. We demonstrate SPP excitation by fluorescent light from crystalline organic para-hexaphenylene nanofibers deposited on a dielectric/metal surface. We characterize the SPPs using angle-resolved leakage radiation spectroscopy, in the excitation wavelength range 420 - 675 nm, corresponding to the nanofiber photoluminescence band. The nanofiber arrangement's capability to act as an SPP coupler for coherent as well as non-coherent excitation indicates its prospect for future integrated systems. To support our experimental results, we investigate the proposed geometries by analytical calculations and finite-difference-time-domain (FDTD) modelling. The experimentally obtained angular leakage radiation peak positions can readily be predicted by our analytical calculations. Nevertheless, the experimental results exhibit a distinct asymmetry in the peak intensities. In agreement with our FDTD calculations, we address this asymmetrical SPP excitation to the nanofiber molecular orientation. The proposed structure's high flexibility, the ease of selective positioning of organic nanofibers, together with the gained insight into its photon-SPP coupling mechanism show great promise towards future local SPP excitation-based integrated devices.

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

PubMed Central

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

2014-01-01

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

Ontogenetic allometry in the foot size of Oligoryzomys flavescens (Waterhouse, 1837) (Rodentia, Sigmodontinae).

PubMed

Maestri, R; Fornel, R; Freitas, T R O; Marinho, J R

2015-05-01

Ontogenetic allometry is the study of how the size or shape of certain structures changes over the course of an animal's development. In this study, using Huxley's formula of allometric growth (1932), we assessed the changes in the rate of growth of the feet size of the sigmodontine rodent Oligoryzomys flavescens during its ontogeny and compared differences between males and females. We find evidence of a change of polarity during the ontogenetic development of the species, with the presence of positive allometry during pregnancy and negative allometry in adulthood. Moreover, we note the presence of sexual dimorphism in the size of the feet, in which males of the species have a higher rate of growth than females. This growth pattern is positively related to escape from predators in childhood in both sexes and, in adulthood, provides a higher encounter rate of females by males, due to the larger displacement of the latter. We suggest that both the forces of natural selection and sexual selection have acted to shape the evolution of foot size in this species.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection.

PubMed

Mendes-Junior, C T; Castelli, E C; Meyer, D; Simões, A L; Donadi, E A

2013-12-01

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3'UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

An attribution theory perspective on emotional labour in nurse-patient encounters: a nested cross-sectional study in paediatric settings.

PubMed

Golfenshtein, Nadya; Drach-Zahavy, Anat

2015-05-01

To understand the role of patients' attributions under the attribution theory framework (locus, controllability, stability) in nurses' performance of surface or deep acting, as they unfold in interactions with different patients. Regulation of emotions at work, or emotional labour, has been conceptualized in terms of two main strategies: surface acting and deep acting. Most prior research tested for between-subject variation in the search for the factors evoking these strategies in nurses, assuming them to be trait-like characteristics. Only scant research has examined how nurses modify their emotional labour strategies in different patient-nurse encounters. A nested cross-sectional design (patients within nurses). Data were collected during 2011-2012 through validated questionnaires from the nursing staff (N = 41) of two paediatric hospital wards and their randomly selected patients (N = 239). Questionnaires were administered to nurses multiple times after encounters with different patients. Analyses were conducted using mixed effects models. In accordance with attribution theory, different combinations of locus, controllability and stability attributions were related to the choice of surface or deep acting. Nurses' perceptions of patients' controllability were associated positively with surface acting and negatively with deep acting. Interaction terms of stability and locus and of controllability and stability, were distinctively associated with deep and surface acting. Findings innovatively introduce the attribution process as an explanatory perspective to nurses' emotional labour and highlight its situational nature, providing a potential tool for emotional labour strategy prediction. Raising nurses' awareness of how they perceive patients may increase control of the strategies employed. © 2015 John Wiley & Sons Ltd.

Steering and filtering white light with resonant waveguide gratings

NASA Astrophysics Data System (ADS)

Quaranta, Giorgio; Basset, Guillaume; Martin, Olivier J. F.; Gallinet, Benjamin

2017-08-01

A novel thin-film single-layer structure based on resonant waveguide gratings (RWGs) allows to engineer selective color filtering and steering of white light. The unit cell of the structure consists of two adjacent finite-length and cross-talking RWGs, where the former acts as in-coupler and the latter acts as out-coupler. The structure is made by only one nano-imprint lithography replication and one thin film layer deposition, making it fully compatible with up-scalable fabrication processes. We characterize a fabricated optical security element designed to work with the flash and the camera of a smartphone in off-axis light steering configuration, where the pattern is revealed only by placing the smartphone in the proper position. Widespread applications are foreseen in a variety of fields, such as multifocal or monochromatic lenses, solar cells, biosensors, security devices and seethrough optical combiners for near-eye displays.

AquaMUNE, a brown seaweed extract, improves metabolism, immune response, energy and chelates heavy metals.

PubMed

1998-01-01

The National Cancer Institute (NCI) has shown interest in the curative powers of ocean plants, many of which appear to possess powerful anti-inflammatory, antiviral, antimicrobial, antifungal, anticancer, and immuno-suppressive properties. AQUAMune, a brown seaweed extract developed by Aqua-10 Laboratories, has gained marketing rights for use as a nutritional supplement. Research shows that it acts as a receptor blocker for many pathogens, including Salmonella, and is effective against Haemophilus pneumonia. AQUAMune is also reported to inhibit outbreaks of genital herpes. Other marine plants are also showing positive curative powers. Evidence reveals that a red marine algae from the Philippines has selective antitumor properties; and that carageenans, a family of sulfated polysaccharides, appear to have anti-viral capabilities. Seaweeds act as natural chelators of heavy metals that improve metabolism in cells, increase ATP production, body temperature, energy levels, and immune function.

Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks.

PubMed

Fogelmark, Karl; Peterson, Carsten; Troein, Carl

2016-01-01

Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated. To investigate the effects of selection in the shaping of transcriptional networks, we derive transcriptional logic from a combinatorially powerful yet tractable model of the binding between DNA and transcription factors. By evolving the resulting networks based on their ability to function as either a simple decision system or a circadian clock, we obtain information on the regulation and logic rules encoded in functional transcriptional networks. Comparisons are made between networks evolved for different functions, as well as with structurally equivalent but non-functional (neutrally evolved) networks, and predictions are validated against the transcriptional network of E. coli. We find that the logic rules governing gene expression depend on the function performed by the network. Unlike the decision systems, the circadian clocks show strong cooperative binding and negative regulation, which achieves tight temporal control of gene expression. Furthermore, we find that transcription factors act preferentially as either activators or repressors, both when binding multiple sites for a single target gene and globally in the transcriptional networks. This separation into positive and negative regulators requires gene duplications, which highlights the interplay between mutation and selection in shaping the transcriptional networks.

Positive Selection at the Polyhomeotic Locus Led to Decreased Thermosensitivity of Gene Expression in Temperate Drosophila melanogaster

PubMed Central

Voigt, Susanne; Laurent, Stefan; Litovchenko, Maria; Stephan, Wolfgang

2015-01-01

Drosophila melanogaster as a cosmopolitan species has successfully adapted to a wide range of different environments. Variation in temperature is one important environmental factor that influences the distribution of species in nature. In particular for insects, which are mostly ectotherms, ambient temperature plays a major role in their ability to colonize new habitats. Chromatin-based gene regulation is known to be sensitive to temperature. Ambient temperature leads to changes in the activation of genes regulated in this manner. One such regulatory system is the Polycomb group (PcG) whose target genes are more expressed at lower temperatures than at higher ones. Therefore, a greater range in ambient temperature in temperate environments may lead to greater variability (plasticity) in the expression of these genes. This might have detrimental effects, such that positive selection acts to lower the degree of the expression plasticity. We provide evidence for this process in a genomic region that harbors two PcG-regulated genes, polyhomeotic proximal (ph-p) and CG3835. We found a signature of positive selection in this gene region in European populations of D. melanogaster and investigated the region by means of reporter gene assays. The target of selection is located in the intergenic fragment between the two genes. It overlaps with the promoters of both genes and an experimentally validated Polycomb response element (PRE). This fragment harbors five sequence variants that are highly differentiated between European and African populations. The African alleles confer a temperature-induced plasticity in gene expression, which is typical for PcG-mediated gene regulation, whereas thermosensitivity is reduced for the European alleles. PMID:25855066

Models of microbiome evolution incorporating host and microbial selection.

PubMed

Zeng, Qinglong; Wu, Steven; Sukumaran, Jeet; Rodrigo, Allen

2017-09-25

Numerous empirical studies suggest that hosts and microbes exert reciprocal selective effects on their ecological partners. Nonetheless, we still lack an explicit framework to model the dynamics of both hosts and microbes under selection. In a previous study, we developed an agent-based forward-time computational framework to simulate the neutral evolution of host-associated microbial communities in a constant-sized, unstructured population of hosts. These neutral models allowed offspring to sample microbes randomly from parents and/or from the environment. Additionally, the environmental pool of available microbes was constituted by fixed and persistent microbial OTUs and by contributions from host individuals in the preceding generation. In this paper, we extend our neutral models to allow selection to operate on both hosts and microbes. We do this by constructing a phenome for each microbial OTU consisting of a sample of traits that influence host and microbial fitnesses independently. Microbial traits can influence the fitness of hosts ("host selection") and the fitness of microbes ("trait-mediated microbial selection"). Additionally, the fitness effects of traits on microbes can be modified by their hosts ("host-mediated microbial selection"). We simulate the effects of these three types of selection, individually or in combination, on microbiome diversities and the fitnesses of hosts and microbes over several thousand generations of hosts. We show that microbiome diversity is strongly influenced by selection acting on microbes. Selection acting on hosts only influences microbiome diversity when there is near-complete direct or indirect parental contribution to the microbiomes of offspring. Unsurprisingly, microbial fitness increases under microbial selection. Interestingly, when host selection operates, host fitness only increases under two conditions: (1) when there is a strong parental contribution to microbial communities or (2) in the absence of a strong parental contribution, when host-mediated selection acts on microbes concomitantly. We present a computational framework that integrates different selective processes acting on the evolution of microbiomes. Our framework demonstrates that selection acting on microbes can have a strong effect on microbial diversities and fitnesses, whereas selection on hosts can have weaker outcomes.

75 FR 50730 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002: Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

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

PubMed

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

2017-01-01

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

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

PubMed Central

Wandeler, Peter; Camenisch, Glauco

2017-01-01

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

Families in Assertive Community Treatment (ACT) Teams in Norway: A Cross-Sectional Study on Relatives' Experiences of Involvement and Alienation.

PubMed

Weimand, B M; Israel, P; Ewertzon, M

2017-11-10

International research shows that relatives of people with mental illness are rarely involved by mental health services. Assertive Community Treatment (ACT) has been recently implemented in Norway. The experience of relatives of ACT users is largely unknown. The aim of this study was to explore relatives' experience with ACT-teams in Norway. Data were collected using the family involvement and alienation questionnaire, consisting of experiences of approach, and alienation from the provision of professional care. 38 Relatives participated in this study. A majority experienced a positive approach (openness, confirmation, and cooperation) from the ACT teams, which also was considered better compared to previous services. They considered openness and cooperation as essential aspects from the professionals. Almost half did not feel alienated (powerlessness and social isolation). Higher level of being approached positively was significantly associated with lower level of feeling alienated. The knowledge of what constituted relatives' positive experiences with the ACT teams should be transferred into practice regarding how to form a positive alliance with relatives.

SB-205384 Is a Positive Allosteric Modulator of Recombinant GABAA Receptors Containing Rat α3, α5, or α6 Subunit Subtypes Coexpressed with β3 and γ2 Subunits

PubMed Central

Heidelberg, Laura S.; Warren, James W.

2013-01-01

Many drugs used to treat anxiety are positive modulators of GABAA receptors, which mediate fast inhibitory neurotransmission. The GABAA receptors can be assembled from a combination of at least 16 different subunits. The receptor’s subunit composition determines its pharmacologic and functional properties, and subunit expression varies throughout the brain. A primary goal for new treatments targeting GABAA receptors is the production of subunit-selective modulators acting upon a discrete population of receptors. The anxiolytic 4-amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SB-205384) is widely considered to be selective for α3-containing GABAA receptors. However, it has been tested only on α1-, α2-, and α3-containing receptors. We examined the activity of SB-205384 at recombinant receptors containing the six different α subunits and found that receptors containing the α3, α5, and α6 subunits were potentiated by SB-205384, with the α6 subunit conferring the greatest responsiveness. Properties associated with chimeric α1/α6 subunits suggested that multiple structural domains influence sensitivity to SB-205384. Point mutations of residues within the extracellular N-terminal domain identified a leucine residue located in loop E of the agonist binding site as an important determinant of high sensitivity to modulation. In the α6 subunit the identity of this residue is species-dependent, with the leucine found in rat subunits but not in human. Our results indicate that SB-205384 is not an α3-selective modulator, and instead acts at several GABAA receptor isoforms. These findings have implications for the side-effect profile of this anxiolytic as well as for its use in neuronal and animal studies as a marker for contribution from α3-containing receptors. PMID:23902941

Small-molecule inhibitors of FGFR, integrins and FAK selectively decrease L1CAM-stimulated glioblastoma cell motility and proliferation.

PubMed

Anderson, Hannah J; Galileo, Deni S

2016-06-01

The cell adhesion/recognition protein L1CAM (L1; CD171) has previously been shown to act through integrin, focal adhesion kinase (FAK) and fibroblast growth factor receptor (FGFR) signaling pathways to increase the motility and proliferation of glioblastoma cells in an autocrine/paracrine manner. Here, we investigated the effects of clinically relevant small-molecule inhibitors of the integrin, FAK and FGFR signaling pathways on glioblastoma-derived cells to determine their effectiveness and selectivity for diminishing L1-mediated stimulation. The effects of the FGFR inhibitor PD173074, the FAK inhibitors PF431396 and Y15 and the αvβ3/αvβ5 integrin inhibitor cilengitide were assessed in L1-positive and L1-negative variants of the human glioblastoma-derived cell lines T98G and U-118 MG. Their motility and proliferation were quantified using time-lapse microscopy and DNA content/cell cycle analyses, respectively. The application of all four inhibitors resulted in reductions in L1-mediated motility and proliferation rates of L1-positive glioblastoma-derived cells, down to the level of L1-negative cells when used at nanomolar concentrations, whereas no or much smaller reductions in these rates were obtained in L1-negative cells. In addition, we found that single inhibitor treatment resulted in maximum effects (i.e., combinations of FAK or integrin inhibitors with the FGFR inhibitor were rarely more effective). These results suggest that FAK may act as a point of convergence between the integrin and FGFR signaling pathways stimulated by L1 in these cells. We here show for the first time that small-molecule inhibitors of FGFR, integrins and FAK effectively and selectively abolish L1-stimulated migration and proliferation of glioblastoma-derived cells. Our results suggest that these inhibitors have the potential to reduce the aggressiveness of high-grade gliomas expressing L1.

Senseless acts as a binary switch during sensory organ precursor selection

NASA Technical Reports Server (NTRS)

Jafar-Nejad, Hamed; Acar, Melih; Nolo, Riitta; Lacin, Haluk; Pan, Hongling; Parkhurst, Susan M.; Bellen, Hugo J.

2003-01-01

During sensory organ precursor (SOP) specification, a single cell is selected from a proneural cluster of cells. Here, we present evidence that Senseless (Sens), a zinc-finger transcription factor, plays an important role in this process. We show that Sens is directly activated by proneural proteins in the presumptive SOPs and a few cells surrounding the SOP in most tissues. In the cells that express low levels of Sens, it acts in a DNA-binding-dependent manner to repress transcription of proneural genes. In the presumptive SOPs that express high levels of Sens, it acts as a transcriptional activator and synergizes with proneural proteins. We therefore propose that Sens acts as a binary switch that is fundamental to SOP selection.

Notification: Evaluation of Enforcement Decree Compliance for Selected Clean Air Act Sources

EPA Pesticide Factsheets

Project #OPE-FY14-0016, May 22, 2014. The Office of Inspector General (OIG) plans to begin the preliminary research phase of an evaluation of enforcement decree compliance for selected Clean Air Act (CAA) sources.

Happiness in action: the impact of positive affect on the time of the conscious intention to act

PubMed Central

Rigoni, Davide; Demanet, Jelle; Sartori, Giuseppe

2015-01-01

The temporal relationship between our conscious intentions to act and the action itself has been widely investigated. Previous research consistently shows that the motor intention enters awareness a few 100 ms before movement onset. As research in other domains has shown that most behavior is affected by the emotional state people are in, it is remarkable that the role of emotional states on intention awareness has never been investigated. Here we tested the hypothesis that positive and negative affects have opposite effects on the temporal relationship between the conscious intention to act and the action itself. A mood induction procedure that combined guided imagery and music listening was employed to induce positive, negative, or neutral affective states. After each mood induction session, participants were asked to execute voluntary self-paced movements and to report when they formed the intention to act. Exposure to pleasant material, as compared to exposure to unpleasant material, enhanced positive affect and dampened negative affect. Importantly, in the positive affect condition participants reported their intention to act earlier in time with respect to action onset, as compared to when they were in the negative or in the neutral affect conditions. Conversely the reported time of the intention to act when participants experienced negative affect did not differ significantly from the neutral condition. These findings suggest that the temporal relationship between the conscious intention to act and the action itself is malleable to changes in affective states and may indicate that positive affect enhances intentional awareness. PMID:26388812

Improvements in manual dexterity relate to improvements in cognitive planning after assisted cycling therapy (ACT) in adolescents with down syndrome.

PubMed

Holzapfel, Simon D; Ringenbach, Shannon D R; Mulvey, Genna M; Sandoval-Menendez, Amber M; Cook, Megan R; Ganger, Rachel O; Bennett, Kristen

2015-01-01

We have previously reported beneficial effects of acute (i.e., single session) Assisted Cycling Therapy (ACT) on manual dexterity and cognitive planning ability in adolescents with Down syndrome (DS). In the present study, we report the chronic effects of eight weeks of ACT, voluntary cycling (VC), and no cycling (NC), on the same measures in adolescents with DS. Participants completed 8 weeks of ACT, VC, or NC. Those in the ACT and VC groups completed 30min sessions three times per week on a stationary bicycle. During ACT, the mechanical motor of the bicycle augmented the cadence to a rate which was on average 79% faster than the voluntary cadence. During VC, the participants pedaled at a self-selected rate. Unimanual dexterity scores as measured with the Purdue Pegboard test (PPT) improved significantly more for the ACT and VC groups compared to the NC group. ACT lead to greater improvements than VC and NC in the assembly sub-test, which is a task that requires more advanced temporal and spatial processing. The ACT group improved significantly more than the VC group and non-significantly more than the NC group in cognitive planning ability as measured by the Tower of London test (ToL). There were also significant correlations between the assembly subtest of the PPT and all measures of the ToL. These correlations were stronger during post-testing than pre-testing. Pre-post changes in the combined PPT score and ToL number of correct moves correlated positively in the ACT group. These results support the efficacy of the salutary effects of ACT on global fine motor function and executive function in DS. Additionally, the performance on complex bimanual dexterity tasks appears to be related to the capacity of cognitive planning ability. This research has important implications for persons with movement deficits that affect activities of daily living. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

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

Sehgal, Neelima; Hlozek, Renee; Addison, Graeme

We present the measured Sunyaev-Zel'dovich (SZ) flux from 474 optically selected MaxBCG clusters that fall within the Atacama Cosmology Telescope (ACT) Equatorial survey region. The ACT Equatorial region used in this analysis covers 510 deg{sup 2} and overlaps Stripe 82 of the Sloan Digital Sky Survey. We also present the measured SZ flux stacked on 52 X-ray-selected MCXC clusters that fall within the ACT Equatorial region and an ACT Southern survey region covering 455 deg{sup 2}. We find that the measured SZ flux from the X-ray-selected clusters is consistent with expectations. However, we find that the measured SZ flux frommore » the optically selected clusters is both significantly lower than expectations and lower than the recovered SZ flux measured by the Planck satellite. Since we find a lower recovered SZ signal than Planck, we investigate the possibility that there is a significant offset between the optically selected brightest cluster galaxies (BCGs) and the SZ centers, to which ACT is more sensitive due to its finer resolution. Such offsets can arise due to either an intrinsic physical separation between the BCG and the center of the gas concentration or from misidentification of the cluster BCG. We find that the entire discrepancy for both ACT and Planck can be explained by assuming that the BCGs are offset from the SZ maxima with a uniform random distribution between 0 and 1.5 Mpc. Such large offsets between gas peaks and BCGs for optically selected cluster samples seem unlikely given that we find the physical separation between BCGs and X-ray peaks for an X-ray-selected subsample of MaxBCG clusters to have a much narrower distribution that peaks within 0.2 Mpc. It is possible that other effects are lowering the ACT and Planck signals by the same amount, with offsets between BCGs and SZ peaks explaining the remaining difference between ACT and Planck measurements. Several effects that can lower the SZ signal equally for both ACT and Planck, but not explain the difference in measured signals, include a larger percentage of false detections in the MaxBCG sample, a lower normalization of the mass-richness relation, radio or infrared galaxy contamination of the SZ flux, and a low intrinsic SZ signal. In the latter two cases, the effects would need to be preferentially more significant in the optically selected MaxBCG sample than in the MCXC X-ray sample.« less

The evolution of recombination in a heterogeneous environment.

PubMed Central

Lenormand, T; Otto, S P

2000-01-01

Most models describing the evolution of recombination have focused on the case of a single population, implicitly assuming that all individuals are equally likely to mate and that spatial heterogeneity in selection is absent. In these models, the evolution of recombination is driven by linkage disequilibria generated either by epistatic selection or drift. Models based on epistatic selection show that recombination can be favored if epistasis is negative and weak compared to directional selection and if the recombination modifier locus is tightly linked to the selected loci. In this article, we examine the joint effects of spatial heterogeneity in selection and epistasis on the evolution of recombination. In a model with two patches, each subject to different selection regimes, we consider the cases of mutation-selection and migration-selection balance as well as the spread of beneficial alleles. We find that including spatial heterogeneity extends the range of epistasis over which recombination can be favored. Indeed, recombination can be favored without epistasis, with negative and even with positive epistasis depending on environmental circumstances. The selection pressure acting on recombination-modifier loci is often much stronger with spatial heterogeneity, and even loosely linked modifiers and free linkage may evolve. In each case, predicting whether recombination is favored requires knowledge of both the type of environmental heterogeneity and epistasis, as none of these factors alone is sufficient to predict the outcome. PMID:10978305

Modeling Linear and Cyclic PKS Intermediates through Atom Replacement

PubMed Central

2015-01-01

The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs. PMID:25406716

29 CFR 825.123 - Unable to perform the functions of the position.

Code of Federal Regulations, 2010 CFR

2010-07-01

... position within the meaning of the Americans with Disabilities Act (ADA), as amended, 42 U.S.C. 12101 et... 29 Labor 3 2010-07-01 2010-07-01 false Unable to perform the functions of the position. 825.123... Act § 825.123 Unable to perform the functions of the position. (a) Definition. An employee is “unable...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 2 2013-04-01 2013-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 2 2012-04-01 2012-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

25 CFR 1000.27 - How does the Director select which Tribes in the applicant pool become self-governance Tribes?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 2 2014-04-01 2014-04-01 false How does the Director select which Tribes in the applicant pool become self-governance Tribes? 1000.27 Section 1000.27 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes...

When bigger is not better: selection against large size, high condition and fast growth in juvenile lemon sharks.

PubMed

Dibattista, J D; Feldheim, K A; Gruber, S H; Hendry, A P

2007-01-01

Selection acting on large marine vertebrates may be qualitatively different from that acting on terrestrial or freshwater organisms, but logistical constraints have thus far precluded selection estimates for the former. We overcame these constraints by exhaustively sampling and repeatedly recapturing individuals in six cohorts of juvenile lemon sharks (450 age-0 and 255 age-1 fish) at an enclosed nursery site (Bimini, Bahamas). Data on individual size, condition factor, growth rate and inter-annual survival were used to test the 'bigger is better', 'fatter is better' and 'faster is better' hypotheses of life-history theory. For age-0 sharks, selection on all measured traits was weak, and generally acted against large size and high condition. For age-1 sharks, selection was much stronger, and consistently acted against large size and fast growth. These results suggest that selective pressures at Bimini may be constraining the evolution of large size and fast growth, an observation that fits well with the observed small size and low growth rate of juveniles at this site. Our results support those of some other recent studies in suggesting that bigger/fatter/faster is not always better, and may often be worse.

Ecological genomics in Xanthomonas: the nature of genetic adaptation with homologous recombination and host shifts.

PubMed

Huang, Chao-Li; Pu, Pei-Hua; Huang, Hao-Jen; Sung, Huang-Mo; Liaw, Hung-Jiun; Chen, Yi-Min; Chen, Chien-Ming; Huang, Ming-Ban; Osada, Naoki; Gojobori, Takashi; Pai, Tun-Wen; Chen, Yu-Tin; Hwang, Chi-Chuan; Chiang, Tzen-Yuh

2015-03-15

Comparative genomics provides insights into the diversification of bacterial species. Bacterial speciation usually takes place with lasting homologous recombination, which not only acts as a cohering force between diverging lineages but brings advantageous alleles favored by natural selection, and results in ecologically distinct species, e.g., frequent host shift in Xanthomonas pathogenic to various plants. Using whole-genome sequences, we examined the genetic divergence in Xanthomonas campestris that infected Brassicaceae, and X. citri, pathogenic to a wider host range. Genetic differentiation between two incipient races of X. citri pv. mangiferaeindicae was attributable to a DNA fragment introduced by phages. In contrast to most portions of the genome that had nearly equivalent levels of genetic divergence between subspecies as a result of the accumulation of point mutations, 10% of the core genome involving with homologous recombination contributed to the diversification in Xanthomonas, as revealed by the correlation between homologous recombination and genomic divergence. Interestingly, 179 genes were under positive selection; 98 (54.7%) of these genes were involved in homologous recombination, indicating that foreign genetic fragments may have caused the adaptive diversification, especially in lineages with nutritional transitions. Homologous recombination may have provided genetic materials for the natural selection, and host shifts likely triggered ecological adaptation in Xanthomonas. To a certain extent, we observed positive selection nevertheless contributed to ecological divergence beyond host shifting. Altogether, mediated with lasting gene flow, species formation in Xanthomonas was likely governed by natural selection that played a key role in helping the deviating populations to explore novel niches (hosts) or respond to environmental cues, subsequently triggering species diversification.

Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators.

PubMed

Forkuo, Gloria S; Nieman, Amanda N; Yuan, Nina Y; Kodali, Revathi; Yu, Olivia B; Zahn, Nicolas M; Jahan, Rajwana; Li, Guanguan; Stephen, Michael Rajesh; Guthrie, Margaret L; Poe, Michael M; Hartzler, Benjamin D; Harris, Ted W; Yocum, Gene T; Emala, Charles W; Steeber, Douglas A; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

2017-06-05

We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α 4 β 3 γ 2 GABA A R selective compound 1 and acidic α 5 β 3 γ 2 selective GABA A R positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties. Additionally, compound 1 reduced the number of lung CD4 + T lymphocytes and directly modulated their transmembrane currents by acting on GABA A Rs. Excellent pharmacokinetic properties were observed, including long plasma half-life (up to 15 h), oral availability, and extremely low brain distribution. In conclusion, we report the selective targeting of GABA A Rs expressed outside the brain and demonstrate reduction of AHR and airway inflammation with two novel orally available GABA A R ligands.

Recombination and selection in the major histocompatibility complex of the endangered forest musk deer (Moschus berezovskii).

PubMed

Cai, Ruibo; Shafer, Aaron B A; Laguardia, Alice; Lin, Zhenzhen; Liu, Shuqiang; Hu, Defu

2015-11-25

The forest musk deer (Moschus berezovskii) is a high elevation species distributed across western China and northern Vietnam. Once abundant, habitat loss and poaching has led to a dramatic decrease in population numbers prompting the IUCN to list the species as endangered. Here, we characterized the genetic diversity of a Major Histocompatibility Complex (MHC) locus and teased apart driving factors shaping its variation. Seven DRB exon 2 alleles were identified among a group of randomly sampled forest musk deer from a captive population in the Sichuan province of China. Compared to other endangered or captive ungulates, forest musk deer have relatively low levels of MHC genetic diversity. Non-synonymous substitutions primarily occurred in the putative peptide-binding region (PBR), with analyses suggesting that recombination and selection has shaped the genetic diversity across the locus. Specifically, inter-allelic recombination generated novel allelic combinations, with evidence for both positive selection acting on the PBR and negative selection on the non-PBR. An improved understanding of functional genetic variability of the MHC will facilitate better design and management of captive breeding programs for this endangered species.

Recovery Act: Planned Efforts and Challenges in Evaluating Compliance with Maintenance of Effort and Similar Provisions. Report to the Republican Leader, U.S. Senate. GAO-10-247

ERIC Educational Resources Information Center

Dodaro, Gene L.

2009-01-01

To help prevent the substitution of federal funds for state, local, or private funds, the American Recovery and Reinvestment Act of 2009 (Recovery Act) contains maintenance of effort and similar provisions requiring that recipients maintain certain levels of spending for selected programs. This report provides information on selected programs in…

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

PubMed Central

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

2007-01-01

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

How immunogenetically different are domestic pigs from wild boars: a perspective from single-nucleotide polymorphisms of 19 immunity-related candidate genes.

PubMed

Chen, Shanyuan; Gomes, Rui; Costa, Vânia; Santos, Pedro; Charneca, Rui; Zhang, Ya-ping; Liu, Xue-hong; Wang, Shao-qing; Bento, Pedro; Nunes, Jose-Luis; Buzgó, József; Varga, Gyula; Anton, István; Zsolnai, Attila; Beja-Pereira, Albano

2013-10-01

The coexistence of wild boars and domestic pigs across Eurasia makes it feasible to conduct comparative genetic or genomic analyses for addressing how genetically different a domestic species is from its wild ancestor. To test whether there are differences in patterns of genetic variability between wild and domestic pigs at immunity-related genes and to detect outlier loci putatively under selection that may underlie differences in immune responses, here we analyzed 54 single-nucleotide polymorphisms (SNPs) of 19 immunity-related candidate genes on 11 autosomes in three pairs of wild boar and domestic pig populations from China, Iberian Peninsula, and Hungary. Our results showed no statistically significant differences in allele frequency and heterozygosity across SNPs between three pairs of wild and domestic populations. This observation was more likely due to the widespread and long-lasting gene flow between wild boars and domestic pigs across Eurasia. In addition, we detected eight coding SNPs from six genes as outliers being under selection consistently by three outlier tests (BayeScan2.1, FDIST2, and Arlequin3.5). Among four non-synonymous outlier SNPs, one from TLR4 gene was identified as being subject to positive (diversifying) selection and three each from CD36, IFNW1, and IL1B genes were suggested as under balancing selection. All of these four non-synonymous variants were predicted as being benign by PolyPhen-2. Our results were supported by other independent lines of evidence for positive selection or balancing selection acting on these four immune genes (CD36, IFNW1, IL1B, and TLR4). Our study showed an example applying a candidate gene approach to identify functionally important mutations (i.e., outlier loci) in wild and domestic pigs for subsequent functional experiments.

Purifying selection and genetic drift shaped Pleistocene evolution of the mitochondrial genome in an endangered Australian freshwater fish.

PubMed

Pavlova, A; Gan, H M; Lee, Y P; Austin, C M; Gilligan, D M; Lintermans, M; Sunnucks, P

2017-05-01

Genetic variation in mitochondrial genes could underlie metabolic adaptations because mitochondrially encoded proteins are directly involved in a pathway supplying energy to metabolism. Macquarie perch from river basins exposed to different climates differ in size and growth rate, suggesting potential presence of adaptive metabolic differences. We used complete mitochondrial genome sequences to build a phylogeny, estimate lineage divergence times and identify signatures of purifying and positive selection acting on mitochondrial genes for 25 Macquarie perch from three basins: Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and Shoalhaven Basin (SB). Phylogenetic analysis resolved basin-level clades, supporting incipient speciation previously inferred from differentiation in allozymes, microsatellites and mitochondrial control region. The estimated time of lineage divergence suggested an early- to mid-Pleistocene split between SB and the common ancestor of HNB+MDB, followed by mid-to-late Pleistocene splitting between HNB and MDB. These divergence estimates are more recent than previous ones. Our analyses suggested that evolutionary drivers differed between inland MDB and coastal HNB. In the cooler and more climatically variable MDB, mitogenomes evolved under strong purifying selection, whereas in the warmer and more climatically stable HNB, purifying selection was relaxed. Evidence for relaxed selection in the HNB includes elevated transfer RNA and 16S ribosomal RNA polymorphism, presence of potentially mildly deleterious mutations and a codon (ATP6 113 ) displaying signatures of positive selection (ratio of nonsynonymous to synonymous substitution rates (dN/dS) >1, radical change of an amino-acid property and phylogenetic conservation across the Percichthyidae). In addition, the difference could be because of stronger genetic drift in the smaller and historically more subdivided HNB with low per-population effective population sizes.

Clownfishes evolution below and above the species level

PubMed Central

Litsios, Glenn; Faye, Laurélène; Salamin, Nicolas

2018-01-01

The difference between rapid morphological evolutionary changes observed in populations and the long periods of stasis detected in the fossil record has raised a decade-long debate about the exact role played by intraspecific mechanisms at the interspecific level. Although they represent different scales of the same evolutionary process, micro- and macroevolution are rarely studied together and few empirical studies have compared the rates of evolution and the selective pressures between both scales. Here, we analyse morphological, genetic and ecological traits in clownfishes at different evolutionary scales and demonstrate that the tempo of molecular and morphological evolution at the species level can be, to some extent, predicted from parameters estimated below the species level, such as the effective population size or the rate of evolution within populations. We also show that similar codons in the gene of the rhodopsin RH1, a light-sensitive receptor protein, are under positive selection at the intra and interspecific scales, suggesting that similar selective pressures are acting at both levels. PMID:29467260

Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

PubMed Central

2014-01-01

Background Genes associated with the neurodevelopmental disorder microcephaly display a strong signature of adaptive evolution in primates. Comparative data suggest a link between selection on some of these loci and the evolution of primate brain size. Whether or not either positive selection or this phenotypic association are unique to primates is unclear, but recent studies in cetaceans suggest at least two microcephaly genes evolved adaptively in other large brained mammalian clades. Results Here we analyse the evolution of seven microcephaly loci, including three recently identified loci, across 33 eutherian mammals. We find extensive evidence for positive selection having acted on the majority of these loci not just in primates but also across non-primate mammals. Furthermore, the patterns of selection in major mammalian clades are not significantly different. Using phylogenetically corrected comparative analyses, we find that the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with neonatal brain size in Glires and Euungulata, the two most densely sampled non-primate clades. Conclusions Together with previous results, this suggests that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals. Nevertheless, several limitations of currently available data and gene-phenotype tests are discussed, including sparse sampling across large evolutionary distances, averaging gene-wide rates of evolution, potential phenotypic variation and evolutionary reversals. We discuss the implications of our results for studies of the genetic basis of brain evolution, and explicit tests of gene-phenotype hypotheses. PMID:24898820

Signatures of positive selection in African Butana and Kenana dairy zebu cattle.

PubMed

Bahbahani, Hussain; Salim, Bashir; Almathen, Faisal; Al Enezi, Fahad; Mwacharo, Joram M; Hanotte, Olivier

2018-01-01

Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds.

Stabilizing selection on sperm number revealed by artificial selection and experimental evolution.

PubMed

Cattelan, Silvia; Di Nisio, Andrea; Pilastro, Andrea

2018-03-01

Sperm competition is taxonomically widespread in animals and is usually associated with large sperm production, being the number of sperm in the competing pool the prime predictor of fertilization success. Despite the strong postcopulatory selection acting directionally on sperm production, its genetic variance is often very high. This can be explained by trade-offs between sperm production and traits associated with mate acquisition or survival, that may contribute to generate an overall stabilizing selection. To investigate this hypothesis, we first artificially selected male guppies (Poecilia reticulata) for high and low sperm production for three generations, while simultaneously removing sexual selection. Then, we interrupted artificial selection and restored sexual selection. Sperm production responded to divergent selection in one generation, and when we restored sexual selection, both high and low lines converged back to the mean sperm production of the original population within two generations, indicating that sperm number is subject to strong stabilizing total sexual selection (i.e., selection acting simultaneously on all traits associated with reproductive success). We discuss the possible mechanisms responsible for the maintenance of high genetic variability in sperm production despite strong selection acting on it. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

I control therefore I do: judgments of agency influence action selection.

PubMed

Karsh, N; Eitam, B

2015-05-01

Our sense of being agents, that is of willingly controlling both our own bodies and the external environment is ubiquitous if thin. Empirical and theoretical work on this 'sense of agency' has documented motivational, cognitive and neural influences on implicit (out of awareness) and explicit (conscious) judgments of agency. For example, fluency of action selection processes has been recently shown to affect judgments of one's degree of control over an external event. However, it is an open question whether and how such judgments of agency act as input to other processes. In this study we demonstrate that the opposite relationship between action selection and judgment of agency also exists. Specifically, we show that manipulating one's objective control over the environment influences both the speed and the frequency of performing an action associated with that control. This pattern bears a striking resemblance to the effect that tangible rewards have on action selection and suggests that positive control feedback is rewarding to the organism, consequently affecting action selection. If further corroborated this 'reward from control' may explain everyday addictions such as prolonged engagement in arcade games and pathological behaviors, such as stereotypy. Copyright © 2015 Elsevier B.V. All rights reserved.

Disruptive ecological selection on a mating cue.

PubMed

Merrill, Richard M; Wallbank, Richard W R; Bull, Vanessa; Salazar, Patricio C A; Mallet, James; Stevens, Martin; Jiggins, Chris D

2012-12-22

Adaptation to divergent ecological niches can result in speciation. Traits subject to disruptive selection that also contribute to non-random mating will facilitate speciation with gene flow. Such 'magic' or 'multiple-effect' traits may be widespread and important for generating biodiversity, but strong empirical evidence is still lacking. Although there is evidence that putative ecological traits are indeed involved in assortative mating, evidence that these same traits are under divergent selection is considerably weaker. Heliconius butterfly wing patterns are subject to positive frequency-dependent selection by predators, owing to aposematism and Müllerian mimicry, and divergent colour patterns are used by closely related species to recognize potential mates. The amenability of colour patterns to experimental manipulation, independent of other traits, presents an excellent opportunity to test their role during speciation. We conducted field experiments with artificial butterflies, designed to match natural butterflies with respect to avian vision. These were complemented with enclosure trials with live birds and real butterflies. Our experiments showed that hybrid colour-pattern phenotypes are attacked more frequently than parental forms. For the first time, we demonstrate disruptive ecological selection on a trait that also acts as a mating cue.

Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies.

PubMed

Cheng, Changde; Kirkpatrick, Mark

2016-09-01

Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. Here we compare the two on a genome-wide scale in humans and flies. We find a distinctive "Twin Peaks" pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. We develop a simple model that successfully recapitulates the Twin Peaks. Our results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies.

A likelihood ratio test for evolutionary rate shifts and functional divergence among proteins

PubMed Central

Knudsen, Bjarne; Miyamoto, Michael M.

2001-01-01

Changes in protein function can lead to changes in the selection acting on specific residues. This can often be detected as evolutionary rate changes at the sites in question. A maximum-likelihood method for detecting evolutionary rate shifts at specific protein positions is presented. The method determines significance values of the rate differences to give a sound statistical foundation for the conclusions drawn from the analyses. A statistical test for detecting slowly evolving sites is also described. The methods are applied to a set of Myc proteins for the identification of both conserved sites and those with changing evolutionary rates. Those positions with conserved and changing rates are related to the structures and functions of their proteins. The results are compared with an earlier Bayesian method, thereby highlighting the advantages of the new likelihood ratio tests. PMID:11734650

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

A Toolbox for Corrective Action: Resource Conservation and Recovery Act Facilities Investigation Remedy Selection Track

EPA Pesticide Factsheets

The purpose of this toolbox is to help EPA Regional staff and their partners to take advantage of the efficiency and quality gains from the Resource Conservation and Recovery Act (RCRA) Facilities Investigation Remedy Selection Track (FIRST) approach.

Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in wild rodents (MURINAE)

PubMed Central

2013-01-01

Background In vertebrates, it has been repeatedly demonstrated that genes encoding proteins involved in pathogen-recognition by adaptive immunity (e.g. MHC) are subject to intensive diversifying selection. On the other hand, the role and the type of selection processes shaping the evolution of innate-immunity genes are currently far less clear. In this study we analysed the natural variation and the evolutionary processes acting on two genes involved in the innate-immunity recognition of Microbe-Associated Molecular Patterns (MAMPs). Results We sequenced genes encoding Toll-like receptor 4 (Tlr4) and 7 (Tlr7), two of the key bacterial- and viral-sensing receptors of innate immunity, across 23 species within the subfamily Murinae. Although we have shown that the phylogeny of both Tlr genes is largely congruent with the phylogeny of rodents based on a comparably sized non-immune sequence dataset, we also identified several potentially important discrepancies. The sequence analyses revealed that major parts of both Tlrs are evolving under strong purifying selection, likely due to functional constraints. Yet, also several signatures of positive selection have been found in both genes, with more intense signal in the bacterial-sensing Tlr4 than in the viral-sensing Tlr7. 92% and 100% of sites evolving under positive selection in Tlr4 and Tlr7, respectively, were located in the extracellular domain. Directly in the Ligand-Binding Region (LBR) of TLR4 we identified two rapidly evolving amino acid residues and one site under positive selection, all three likely involved in species-specific recognition of lipopolysaccharide of gram-negative bacteria. In contrast, all putative sites of LBRTLR7 involved in the detection of viral nucleic acids were highly conserved across rodents. Interspecific differences in the predicted 3D-structure of the LBR of both Tlrs were not related to phylogenetic history, while analyses of protein charges clearly discriminated Rattini and Murini clades. Conclusions In consequence of the constraints given by the receptor protein function purifying selection has been a dominant force in evolution of Tlrs. Nevertheless, our results show that episodic diversifying parasite-mediated selection has shaped the present species-specific variability in rodent Tlrs. The intensity of diversifying selection was higher in Tlr4 than in Tlr7, presumably due to structural properties of their ligands. PMID:24028551

Positive effect of specific low-frequency electrical stimulation during short-term recovery on subsequent high-intensity exercise.

PubMed

Bieuzen, François; Borne, Rachel; Toussaint, Jean-François; Hausswirth, Christophe

2014-02-01

The objective of this study was to test how low-frequency electrical stimulation (LFES; Veinoplus Sport (AdRem Technology, Paris, France)) of the calf muscles affects recovery indices compared with 2 other commonly used recovery methods (active, ACT; passive, PAS). The tests used assessed predominantly anaerobic performance after short-term (15 min) recovery, and the kinetics of blood markers. Fourteen highly trained female handball players completed 2 Yo-Yo Intermittent Recovery tests (level 2; YYIR2) separated by a 15-min recovery period. During recovery, 1 of 3 recovery methods (ACT, LFES or PAS) was randomly selected. Performance (i.e., distance run) was measured at the end of each YYIR2 test. Blood lactate, pH, bicarbonate concentrations, heart rate, respiratory gas exchange and tissue saturation index for the lateral gastrocnemius were recorded. LFES showed a very likely beneficial effect on performance during the second YYIR2 relative to PAS and a possible beneficial effect relative to ACT (distance Pre vs. Post; LFES: -1.8%; ACT: -7.6%; PAS: -15.9%). Compared with PAS recovery, LFES and ACT recovery clearly showed a faster return to baseline for blood lactate, pH and bicarbonate concentrations during the recovery period. LFES of the calf muscles and, to a lesser extent, ACT recovery appear to effectively improve short-term recovery between 2 bouts of exhausting exercises. These methods could be of benefit if applied during half-time, for sports involving successive rounds, or where only a limited recovery period is available.

Determinants of long acting and permanent contraceptive methods utilization among married women of reproductive age groups in western Ethiopia: a cross-sectional study.

PubMed

Melka, Alemu Sufa; Tekelab, Tesfalidet; Wirtu, Desalegn

2015-01-01

In Ethiopia information on the level of utilization of the long term and permanent contraceptive methods and associated factorsis lacking. The aim of this study was to understand the determinant factors of long acting and permanent contraceptive methods use among married women of reproductive age in Western Ethiopia. A community based cross-sectional study design was employed. Multi stage sampling was used to select 1003 study participants. Data was collected from April 10 to April 25,2014 using a pre- tested structured questionnaire. The data were entered using Epi-info version 3.5.1 and exported to SPSS version 20 for analysis. Multivariate logistic regression analysis was done to identify predictors of long acting and permanent contraceptive methods at 95% CL. Use of long acting and permanent contraceptive methods in this study was found to be 20%. Survey results showed a significant positive association between utilization of long acting and permanent contraceptive methods and women's education (AOR=1.72, 95%CI=1.02-3.05), women's occupation (AOR=2.01, 95% CI=1.11-3.58), number of live children (AOR=2.42, 95% CI: 1.46-4.02), joint fertility related decision (AOR=6.11, 95% CI: 2.29-16.30), having radio/TV (AOR=2.31, 95% CI: 1.40-3.80), and discussion with health care provider about long acting and permanent contraceptive methods (AOR=13.72, 95% CI: 8.37-22.47). Efforts need to be aimed at women empowerment, health education, and encouraging open discussion of family planning by couples.

The Atacama Cosmology Telescope: Relation Between Galaxy Cluster Optical Richness and Sunyaev-Zel'dovich Effect

NASA Technical Reports Server (NTRS)

Sehgal, Neelima; Addison, Graeme; Battaglia, Nick; Battistelli, Elia S.; Bond, J. Richard; Das, Sudeep; Devlin, Mark J.; Dunkley, Joanna; Duenner, Rolando; Gralla, Megan;

The metabotropic glutamate receptors: structure, activation mechanism and pharmacology.

PubMed

Pin, Jean-Philippe; Acher, Francine

2002-06-01

The metabotropic glutamate receptors are G-protein coupled receptors (GPCR) involved in the regulation of many synapses, including most glutamatergic fast excitatory synapses. Eight subtypes have been identified that can be classified into three groups. The molecular characterization of these receptors revealed proteins much more complex than any other GPCRs. They are composed of a Venus Flytrap (VFT) module where glutamate binds, connected to a heptahelical domain responsible for G-protein coupling. Recent data including the structure of the VFT module determined with and without glutamate, indicate that these receptors function as dimers. Moreover a number of intracellular proteins can regulate their targeting and transduction mechanism. Such structural features of mGlu receptors offer multiple possibilities for synthetic compounds to modulate their activity. In addition to agonists and competitive antagonists acting at the glutamate binding site, a number of non-competitive antagonists with inverse agonist activity, and positive allosteric modulators have been discovered. These later compounds share specific properties that make them good candidates for therapeutic applications. First, their non-amino acid structure makes them pass more easily the blood brain barrier. Second, they are much more selective than any other compound identified so far, being the first subtype selective molecules. Third, for the negative modulators, their non competitive mechanism of action makes them relatively unaffected by high concentrations of glutamate that may be present in disease states (e.g. stroke, epilepsy, neuropathic pain, etc.). Fourth, like the benzodiazepines acting at the GABA(A) receptors, the positive modulators offer a new way to increase the activity of these receptors in vivo, with a low risk of inducing their desensitization. The present review article focuses on the specific structural features of these receptors and highlights the various possibilities these offer for drug development.

The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents.

PubMed

Griebel, Guy; Stemmelin, Jeanne; Lopez-Grancha, Mati; Fauchey, Valérie; Slowinski, Franck; Pichat, Philippe; Dargazanli, Gihad; Abouabdellah, Ahmed; Cohen, Caroline; Bergis, Olivier E

2018-02-05

Enhancing endogenous cannabinoid (eCB) signaling has been considered as a potential strategy for the treatment of stress-related conditions. Fatty acid amide hydrolase (FAAH) represents the primary degradation enzyme of the eCB anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). This study describes a potent reversible FAAH inhibitor, SSR411298. The drug acts as a selective inhibitor of FAAH, which potently increases hippocampal levels of AEA, OEA and PEA in mice. Despite elevating eCB levels, SSR411298 did not mimic the interoceptive state or produce the behavioral side-effects (memory deficit and motor impairment) evoked by direct-acting cannabinoids. When SSR411298 was tested in models of anxiety, it only exerted clear anxiolytic-like effects under highly aversive conditions following exposure to a traumatic event, such as in the mouse defense test battery and social defeat procedure. Results from experiments in models of depression showed that SSR411298 produced robust antidepressant-like activity in the rat forced-swimming test and in the mouse chronic mild stress model, restoring notably the development of inadequate coping responses to chronic stress. This preclinical profile positions SSR411298 as a promising drug candidate to treat diseases such as post-traumatic stress disorder, which involves the development of maladaptive behaviors.

77 FR 16888 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

... Change To Delete Certain Select Symbols From the Rebates and Fees for Adding and Removing Liquidity in Select Symbols March 15, 2012. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act... [[Page 16889

Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks

PubMed Central

Fogelmark, Karl; Peterson, Carsten; Troein, Carl

2016-01-01

Background Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated. Methodology To investigate the effects of selection in the shaping of transcriptional networks, we derive transcriptional logic from a combinatorially powerful yet tractable model of the binding between DNA and transcription factors. By evolving the resulting networks based on their ability to function as either a simple decision system or a circadian clock, we obtain information on the regulation and logic rules encoded in functional transcriptional networks. Comparisons are made between networks evolved for different functions, as well as with structurally equivalent but non-functional (neutrally evolved) networks, and predictions are validated against the transcriptional network of E. coli. Principal Findings We find that the logic rules governing gene expression depend on the function performed by the network. Unlike the decision systems, the circadian clocks show strong cooperative binding and negative regulation, which achieves tight temporal control of gene expression. Furthermore, we find that transcription factors act preferentially as either activators or repressors, both when binding multiple sites for a single target gene and globally in the transcriptional networks. This separation into positive and negative regulators requires gene duplications, which highlights the interplay between mutation and selection in shaping the transcriptional networks. PMID:26927540

Complex patterns of multivariate selection on the ejaculate of a broadcast spawning marine invertebrate.

PubMed

Fitzpatrick, John L; Simmons, Leigh W; Evans, Jonathan P

2012-08-01

Assessing how selection operates on several, potentially interacting, components of the ejaculate is a challenging endeavor. Ejaculates can be subject to natural and/or sexual selection, which can impose both linear (directional) and nonlinear (stabilizing, disruptive, and correlational) selection on different ejaculate components. Most previous studies have examined linear selection of ejaculate components and, consequently, we know very little about patterns of nonlinear selection on the ejaculate. Even less is known about how selection acts on the ejaculate as a functionally integrated unit, despite evidence of covariance among ejaculate components. Here, we assess how selection acts on multiple ejaculate components simultaneously in the broadcast spawning sessile invertebrate Mytilus galloprovincialis using the statistical tools of multivariate selection analyses. Our analyses of relative fertilization rates revealed complex patterns of selection on sperm velocity, motility, and morphology. Interestingly, the most successful ejaculates were made up of slower swimming sperm with relatively low percentages of motile cells, and sperm with smaller head volumes that swam in highly pronounced curved swimming trajectories. These results are consistent with an emerging body of literature on fertilization kinetics in broadcast spawners, and shed light on the fundamental nature of selection acting on the ejaculate as a functionally integrated unit. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Which Moral Foundations Predict Willingness to Make Lifestyle Changes to Avert Climate Change in the USA?

PubMed Central

Dickinson, Janis L.; McLeod, Poppy; Bloomfield, Robert; Allred, Shorna

2016-01-01

Jonathan Haidt’s Moral Foundations Theory identifies five moral axes that can influence human motivation to take action on vital problems like climate change. The theory focuses on five moral foundations, including compassion, fairness, purity, authority, and ingroup loyalty; these have been found to differ between liberals and conservatives as well as Democrats and Republicans. Here we show, based on the Cornell National Social Survey (USA), that valuations of compassion and fairness were strong, positive predictors of willingness to act on climate change, whereas purity had a non-significant tendency in the positive direction (p = 0.07). Ingroup loyalty and authority were not supported as important predictor variables using model selection (ΔAICc__). Compassion and fairness were more highly valued by liberals, whereas purity, authority, and in-group loyalty were more highly valued by conservatives. As in previous studies, participants who were younger, more liberal, and reported greater belief in climate change, also showed increased willingness to act on climate change. Our research supports the potential importance of moral foundations as drivers of intentions with respect to climate change action, and suggests that compassion, fairness, and to a lesser extent, purity, are potential moral pathways for personal action on climate change in the USA. PMID:27760207

Conduction Properties of KcsA Measured Using Brownian Dynamics with Flexible Carbonyl Groups in the Selectivity Filter

PubMed Central

Chung, Shin-Ho; Corry, Ben

2007-01-01

In the narrow segment of an ion conducting pathway, it is likely that a permeating ion influences the positions of the nearby atoms that carry partial or full electronic charges. Here we introduce a method of incorporating the motion of charged atoms lining the pore into Brownian dynamics simulations of ion conduction. The movements of the carbonyl groups in the selectivity filter of the KcsA channel are calculated explicitly, allowing their bond lengths, bond angles, and dihedral angels to change in response to the forces acting upon them. By systematically changing the coefficients of bond stretching and of angle bending, the carbon and oxygen atoms can be made to fluctuate from their fixed positions by varying mean distances. We show that incorporating carbonyl motion in this way does not alter the mechanism of ion conduction and only has a small influence on the computed current. The slope conductance of the channel increases by ∼25% when the root mean-square fluctuations of the carbonyl groups are increased from 0.01 to 0.61 Å. The energy profiles and the number of resident ions in the channel remain unchanged. The method we utilized here can be extended to allow the movement of glutamate or aspartate side chains lining the selectivity filters of other ionic channels. PMID:17434934

Conduction properties of KcsA measured using brownian dynamics with flexible carbonyl groups in the selectivity filter.

PubMed

Chung, Shin-Ho; Corry, Ben

2007-07-01

In the narrow segment of an ion conducting pathway, it is likely that a permeating ion influences the positions of the nearby atoms that carry partial or full electronic charges. Here we introduce a method of incorporating the motion of charged atoms lining the pore into Brownian dynamics simulations of ion conduction. The movements of the carbonyl groups in the selectivity filter of the KcsA channel are calculated explicitly, allowing their bond lengths, bond angles, and dihedral angels to change in response to the forces acting upon them. By systematically changing the coefficients of bond stretching and of angle bending, the carbon and oxygen atoms can be made to fluctuate from their fixed positions by varying mean distances. We show that incorporating carbonyl motion in this way does not alter the mechanism of ion conduction and only has a small influence on the computed current. The slope conductance of the channel increases by approximately 25% when the root mean-square fluctuations of the carbonyl groups are increased from 0.01 to 0.61 A. The energy profiles and the number of resident ions in the channel remain unchanged. The method we utilized here can be extended to allow the movement of glutamate or aspartate side chains lining the selectivity filters of other ionic channels.

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2012 CFR

2012-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2013 CFR

2013-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2014 CFR

2014-07-01

... always stay in a “fire safe” facility. This is a facility that meets the fire safety requirements of the Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a...

20 CFR 670.420 - Are there any special requirements for enrollment related to the Military Selective Service Act?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., each male applicant 18 years of age or older must present evidence that he has complied with section 3 of the Military Selective Service Act (50 U.S.C. App. 451 et seq.) if required; and (b) When a male...

Microsoft kinect-based artificial perception system for control of functional electrical stimulation assisted grasping.

PubMed

Strbac, Matija; Kočović, Slobodan; Marković, Marko; Popović, Dejan B

2014-01-01

We present a computer vision algorithm that incorporates a heuristic model which mimics a biological control system for the estimation of control signals used in functional electrical stimulation (FES) assisted grasping. The developed processing software acquires the data from Microsoft Kinect camera and implements real-time hand tracking and object analysis. This information can be used to identify temporal synchrony and spatial synergies modalities for FES control. Therefore, the algorithm acts as artificial perception which mimics human visual perception by identifying the position and shape of the object with respect to the position of the hand in real time during the planning phase of the grasp. This artificial perception used within the heuristically developed model allows selection of the appropriate grasp and prehension. The experiments demonstrate that correct grasp modality was selected in more than 90% of tested scenarios/objects. The system is portable, and the components are low in cost and robust; hence, it can be used for the FES in clinical or even home environment. The main application of the system is envisioned for functional electrical therapy, that is, intensive exercise assisted with FES.

Microsoft Kinect-Based Artificial Perception System for Control of Functional Electrical Stimulation Assisted Grasping

PubMed Central

Kočović, Slobodan; Popović, Dejan B.

2014-01-01

We present a computer vision algorithm that incorporates a heuristic model which mimics a biological control system for the estimation of control signals used in functional electrical stimulation (FES) assisted grasping. The developed processing software acquires the data from Microsoft Kinect camera and implements real-time hand tracking and object analysis. This information can be used to identify temporal synchrony and spatial synergies modalities for FES control. Therefore, the algorithm acts as artificial perception which mimics human visual perception by identifying the position and shape of the object with respect to the position of the hand in real time during the planning phase of the grasp. This artificial perception used within the heuristically developed model allows selection of the appropriate grasp and prehension. The experiments demonstrate that correct grasp modality was selected in more than 90% of tested scenarios/objects. The system is portable, and the components are low in cost and robust; hence, it can be used for the FES in clinical or even home environment. The main application of the system is envisioned for functional electrical therapy, that is, intensive exercise assisted with FES. PMID:25202707

Implementation of the Tribally Controlled Community Colleges Assistance Act. Hearing Before the Select Committee on Indian Affairs, United States Senate, Ninety-Sixth Congress, Second Session on P.L. 95-471, The Tribally Controlled Community Colleges Assistance Act, June 10, 1980.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

Meeting on June 10, 1980, the Select Committee on Indian Affairs heard testimony on the first-year implementation of Public Law 95-471, the Tribally Controlled Community Colleges Assistance Act of 1978. Testimony consisted of problems encountered during the first year, expectations for next year, and recommendations for change. The director of the…

On the irrationality of emotion and the rationality of awareness.

PubMed

Lambie, John A

2008-09-01

It is argued that one answer to the question of the rationality of emotion hinges on the different roles in action selection played by emotions when one is aware of them versus when one is not aware of them (awareness being indexed by the ability to report one's emotion). When unaware of one's emotions, they are: (a) not able to enter into one's deliberations about what to do, and (b) more likely to be automatically acted out. This is a problem for rationality because (partly due to the logic of signal detection theory) emotional action urges are often "false positives". In contrast, awareness of emotions crucially allows emotional responses to be inhibited: such inhibition is necessary for truly rational action selection. Furthermore, awareness enables Reflective Revision--the modification of one's theories and action plans as a result of awareness of inconsistencies between theories and data, and action plans and goals.

Molecular and Evolutionary History of Melanism in North American Gray Wolves

PubMed Central

Anderson, Tovi M.; vonHoldt, Bridgett M.; Candille, Sophie I.; Musiani, Marco; Greco, Claudia; Stahler, Daniel R.; Smith, Douglas W.; Padhukasahasram, Badri; Randi, Ettore; Leonard, Jennifer A.; Bustamante, Carlos D.; Ostrander, Elaine A.; Tang, Hua; Wayne, Robert K.; Barsh, Gregory S.

2010-01-01

Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives. PMID:19197024

Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA

NASA Astrophysics Data System (ADS)

Ziach, Krzysztof; Chollet, Céline; Parissi, Vincent; Prabhakaran, Panchami; Marchivie, Mathieu; Corvaglia, Valentina; Bose, Partha Pratim; Laxmi-Reddy, Katta; Godde, Frédéric; Schmitter, Jean-Marie; Chaignepain, Stéphane; Pourquier, Philippe; Huc, Ivan

2018-05-01

Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. These molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer-protein interactions, whereas sequence-selective enzymes were not inhibited. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein-DNA interactions.

Molecular and evolutionary history of melanism in North American gray wolves.

PubMed

Anderson, Tovi M; vonHoldt, Bridgett M; Candille, Sophie I; Musiani, Marco; Greco, Claudia; Stahler, Daniel R; Smith, Douglas W; Padhukasahasram, Badri; Randi, Ettore; Leonard, Jennifer A; Bustamante, Carlos D; Ostrander, Elaine A; Tang, Hua; Wayne, Robert K; Barsh, Gregory S

2009-03-06

Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives.

Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies

PubMed Central

Kirkpatrick, Mark

2016-01-01

Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. Here we compare the two on a genome-wide scale in humans and flies. We find a distinctive “Twin Peaks” pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. We develop a simple model that successfully recapitulates the Twin Peaks. Our results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies. PMID:27658217

Nutrient, organic carbon, and chloride concentrations and loads in selected Long Island Sound tributaries—Four decades of change following the passage of the Federal Clean Water Act

USGS Publications Warehouse

Mullaney, John R.

2016-03-10

Loads of dissolved silica (DSi; flow-normalized and non-flow-normalized) increased slightly at most stations during the study period and were positively correlated to urbanized land in the basin and negatively correlated to area of open water. Concentrations and loads of chloride increased at 12 of the 14 sites during both periods. Increases likely are the result of an increase in the use of salt for deicing, as well as other factors related to urbanization and population growth, such as increases in wastewater discharge and discharge from septic systems.

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

PubMed

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

2011-02-01

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

Selective Moral Disengagement in the Exercise of Moral Agency.

ERIC Educational Resources Information Center

Bandura, Albert

2002-01-01

Addresses the issue of selective moral disengagement in the exercise of moral agency. Argues that moral functioning is governed by self-reactive selfhood rather than by dispassionate abstract reasoning. Concludes that the massive threats to human welfare stem mainly from deliberate acts of principle rather than from unrestrained acts of impulse.…

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

36 CFR 292.41 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Earth's crust prior to the Holocene epoch. Selective cutting means single tree or group selection... equipment means any contrivance which travels over ground, snow or water on wheels, tracks, skids, or by... the Mining Act of 1872, 30 U.S.C. 22 et seq., and the Mineral Leasing Act of 1920, 30 U.S.C. 181 et...

Reauthorization of the Higher Education Act by the 96th Congress--Selected Issues.

ERIC Educational Resources Information Center

Stedman, Jim

Selected issues to be considered by the 96th Congress regarding the Higher Education Act reauthorization are examined. Recently funded at approximately $5 billion, the programs of this legislation serve over 3 million students through financial assistance and nearly the full range of traditional higher education institutions and many proprietary…

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

PubMed Central

Basu, Swaraj; Larsson, Erik

2016-01-01

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

Behavioural fever is a synergic signal amplifying the innate immune response.

PubMed

Boltaña, Sebastian; Rey, Sonia; Roher, Nerea; Vargas, Reynaldo; Huerta, Mario; Huntingford, Felicity Anne; Goetz, Frederick William; Moore, Janice; Garcia-Valtanen, Pablo; Estepa, Amparo; Mackenzie, S

2013-09-07

Behavioural fever, defined as an acute change in thermal preference driven by pathogen recognition, has been reported in a variety of invertebrates and ectothermic vertebrates. It has been suggested, but so far not confirmed, that such changes in thermal regime favour the immune response and thus promote survival. Here, we show that zebrafish display behavioural fever that acts to promote extensive and highly specific temperature-dependent changes in the brain transcriptome. The observed coupling of the immune response to fever acts at the gene-environment level to promote a robust, highly specific time-dependent anti-viral response that, under viral infection, increases survival. Fish that are not offered a choice of temperatures and that therefore cannot express behavioural fever show decreased survival under viral challenge. This phenomenon provides an underlying explanation for the varied functional responses observed during systemic fever. Given the effects of behavioural fever on survival and the fact that it exists across considerable phylogenetic space, such immunity-environment interactions are likely to be under strong positive selection.

Space Weather Research in the Equatorial Region: A Philosophical Reinforcement

NASA Astrophysics Data System (ADS)

Chukwuma, Victor; Odunaike, Rasaki; Laoye, John

Investigations using radio waves reflected from the ionosphere, at high-and mid-latitudes indicate that ionospheric absorption can strongly increase following geomagnetic storms; which appears to suggest some definite relationship between ionospheric radio wave absorption and geomagnetic storms at these latitudes. However, corresponding earlier studies in the equatorial region did not appear to show any explicit relationship between ionospheric radio wave absorption and geomagnetic storm activity. This position appeared acceptable to the existing scientific paradigm, until in an act of paradigm shift, by a change of storm selection criteria, some more recent space weather investigations in the low latitudes showed that ionospheric radio wave absorption in the equatorial region clearly increases after intense storms. Given that these results in the equatorial region stood against the earlier results, this paper presently attempts to highlight their philosophical underpinning and posit that they constitute a scientific statement.

The effect of moisture content within multilayer protective clothing on protection from radiation and steam.

PubMed

Su, Yun; Li, Jun; Song, Guowen

2018-06-01

The moisture from skin sweat and atmospheric water affects the thermal protective performance provided by multilayer protective clothing. Four levels of moisture content were selected to evaluate the impact of moisture on thermal protection under dry (thermal radiation) and wet (thermal radiation and low-pressure steam) heat exposure. Also, the role of moisture and its relationship with exposure time were analyzed based on skin heat flux and Henriques integral value. The addition of moisture to a fabric system was found to result in differences in second-degree and third-degree skin burn times. When moisture is added to a fabric system, it both acts as a thermal conductor to present a negative effect and provides a positive effect owing to thermal storage of water and evaporative heat loss. The positive or negative effects of moisture are mainly dependent on the thermal exposure time, the moisture content and the presence of hot steam.

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

PubMed

Parto, Sahar; Lartillot, Nicolas

2017-06-23

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

Comparing Non-Medical Sex Selection and Saviour Sibling Selection in the Case of JS and LS v Patient Review Panel: Beyond the Welfare of the Child?

PubMed

Smith, Malcolm K; Taylor-Sands, Michelle

2018-03-01

The national ethical guidelines relevant to assisted reproductive technology (ART) have recently been reviewed by the National Health and Medical Research Council (NHMRC). The review process paid particular attention to the issue of non-medical sex selection, although ultimately, the updated ethical guidelines maintain the pre-consultation position of a prohibition on non-medical sex selection. Whilst this recent review process provided a public forum for debate and discussion of this ethically contentious issue, the Victorian case of JS and LS v Patient Review Panel (Health and Privacy) [2011] VCAT 856 provides a rare instance where the prohibition on non-medical sex selection has been explored by a court or tribunal in Australia. This paper analyses the reasoning in that decision, focusing specifically on how the Victorian Civil and Administrative Tribunal applied the statutory framework relevant to ART and its comparison to other uses of embryo selection technologies. The Tribunal relied heavily upon the welfare-of-the-child principle under the Assisted Reproductive Treatment Act 2008 (Vic). The Tribunal also compared non-medical sex selection with saviour sibling selection (that is, where a child is purposely conceived as a matched tissue donor for an existing child of the family). Our analysis leads us to conclude that the Tribunal's reasoning fails to adequately justify the denial of the applicants' request to utilize ART services to select the sex of their prospective child.

Signatures of positive selection in African Butana and Kenana dairy zebu cattle

PubMed Central

Salim, Bashir; Almathen, Faisal; Al Enezi, Fahad; Mwacharo, Joram M.; Hanotte, Olivier

2018-01-01

Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds. PMID:29300786

Sulfadiazine-selective determination in aquaculture environment: selective potentiometric transduction by neutral or charged ionophores.

PubMed

Almeida, S A A; Heitor, A M; Montenegro, M C B S M; Sales, M G F

2011-09-15

Solid-contact sensors for the selective screening of sulfadiazine (SDZ) in aquaculture waters are reported. Sensor surfaces were made from PVC membranes doped with tetraphenylporphyrin-manganese(III) chloride, α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin ionophores that were dispersed in plasticizer. Some membranes also presented a positive or a negatively charged additive. Phorphyrin-based sensors relied on a charged carrier mechanism. They exhibited a near-Nernstian response with slopes of 52 mV decade(-1) and detection limits of 3.91×10(-5) mol L(-1). The addition of cationic lipophilic compounds to the membrane originated Nernstian behaviours, with slopes ranging 59.7-62.0 mV decade(-1) and wider linear ranges. Cyclodextrin-based sensors acted as neutral carriers. In general, sensors with positively charged additives showed an improved potentiometric performance when compared to those without additive. Some SDZ selective membranes displayed higher slopes and extended linear concentration ranges with an increasing amount of additive (always <100% ionophore). The sensors were independent from the pH of test solutions within 2-7. The sensors displayed fast response, always <15s. In general, a good discriminating ability was found in real sample environment. The sensors were successfully applied to the fast screening of SDZ in real waters samples from aquaculture fish farms. The method offered the advantages of simplicity, accuracy, and automation feasibility. The sensing membrane may contribute to the development of small devices allowing in locus measurements of sulfadiazine or parent-drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda

PubMed Central

Mavoko, Hypolite Muhindo; Nabasumba, Carolyn; Francis, Filbert; Lutumba, Pascal; Alifrangis, Michael; Van geertruyden, Jean-Pierre

2018-01-01

Background The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings. Methods P. falciparum positive samples were collected from children aged 12–59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays. Results The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11–1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42–2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms. Conclusion We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines. PMID:29390014

Genetic evidence for extreme polyandry and extraordinary sex-role reversal in a pipefish.

PubMed

Jones, A G; Walker, D; Avise, J C

2001-12-22

Due to the phenomenon of male pregnancy, the fish family Syngnathidae (seahorses and pipefishes) has historically been considered an archetypal example of a group in which sexual selection should act more strongly on females than on males. However, more recent work has called into question the idea that all species with male pregnancy are sex-role reversed with respect to the intensity of sexual selection. Furthermore, no studies have formally quantified the opportunity for sexual selection in any natural breeding assemblage of pipefishes or seahorses in order to demonstrate conclusively that sexual selection acts most strongly on females. Here, we use a DNA-based study of parentage in the Gulf pipefish Syngnathus scovelli in order to show that sexual selection indeed acts more strongly on females than on males in this species. Moreover, the Gulf pipefish exhibits classical polyandry with the greatest asymmetry in reproductive roles (as quantified by variances in mating success) between males and females yet documented in any system. Thus, the intensity of sexual selection on females in pipefish rivals that of any other taxon yet studied.

Genetic evidence for extreme polyandry and extraordinary sex-role reversal in a pipefish.

PubMed Central

Jones, A. G.; Walker, D.; Avise, J. C.

2001-01-01

Due to the phenomenon of male pregnancy, the fish family Syngnathidae (seahorses and pipefishes) has historically been considered an archetypal example of a group in which sexual selection should act more strongly on females than on males. However, more recent work has called into question the idea that all species with male pregnancy are sex-role reversed with respect to the intensity of sexual selection. Furthermore, no studies have formally quantified the opportunity for sexual selection in any natural breeding assemblage of pipefishes or seahorses in order to demonstrate conclusively that sexual selection acts most strongly on females. Here, we use a DNA-based study of parentage in the Gulf pipefish Syngnathus scovelli in order to show that sexual selection indeed acts more strongly on females than on males in this species. Moreover, the Gulf pipefish exhibits classical polyandry with the greatest asymmetry in reproductive roles (as quantified by variances in mating success) between males and females yet documented in any system. Thus, the intensity of sexual selection on females in pipefish rivals that of any other taxon yet studied. PMID:11749706

The effects of restaurant nutrition menu labelling on college students' healthy eating behaviours.

PubMed

Roseman, Mary G; Joung, Hyun-Woo; Choi, Eun-Kyong Cindy; Kim, Hak-Seon

2017-04-01

According to the US Affordable Care Act, restaurant chains are required to provide energy (calorie) and other nutrition information on their menu. The current study examined the impact of menu labelling containing calorie information and recommended daily calorie intake, along with subjective nutrition knowledge, on intention to select lower-calorie foods prior to the implementation of the Affordable Care Act. Full factorial experimental design with participants exposed to four variants of a sample menu in a 2 (presence v. absence of calorie information) ×2 (presence v. absence of recommended daily calorie intake). Large, public university in the Southwest USA. Primarily undergraduate college students. Majority of participants were 19-23 years of age (mean 21·8 (sd 3·6) years). Menu information about calorie content and respondents' subjective nutrition knowledge had a significantly positive impact on students' intention to select lower-calorie foods (β=0·24, P<0·001 and β=0·33, P<0·001, respectively); however, recommended daily calorie intake information on the menu board did not influence students' intention to select lower-calorie foods (β=0·10, P=0·105). Gender played a significant role on purchase intent for lower-calorie menu items, with females more affected by the calorie information than males (β=0·37, P<0·001). Findings support the role menu labelling can play in encouraging a healthier lifestyle for college students. College students who are Generation Y desire healthier menu options and accept nutritional labels on restaurant menus as a way to easily and expediently obtain nutrition information.

77 FR 62283 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... using a Nasdaq Workstation or Weblink ACT 2.0 user account. Member firms subscribing to the ACT Reject... Workstation and Weblink ACT 2.0 user account selected for subscription to the ACT Reject Scan service. Nasdaq..., per month. Use of the ACT Reject Scan service is voluntary and the subscription fee will be imposed on...

Refinery siting workbook: appendices C to O

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

Not Available

Applicable laws and permits available for the selection and building of petroleum refineries are enclosed. A glossary of pertinent terms is also included. References related to the National Environmental Policy Act, the Clean Air Act, the Federal Water Pollution Control Act, Resource Conservation and Recovery Act, Toxic Substance Control Act, and Wetlands and Coastal Zone are included. Permit information is also presented. (DC)

Selection for sex in finite populations.

PubMed

Roze, D

2014-07-01

Finite population size generates interference between selected loci, which has been shown to favour increased rates of recombination. In this article, I present different analytical models exploring selection acting on a 'sex modifier locus' (that affects the relative investment into asexual and sexual reproduction) in a finite population. Two forms of selective forces act on the modifier: direct selection due to intrinsic costs associated with sexual reproduction and indirect selection generated by one or two other loci affecting fitness. The results show that indirect selective forces differ from those acting on a recombination modifier even in the case of a haploid population: in particular, a single selected locus generates indirect selection for sex, while two loci are required in the case of a recombination modifier. This effect stems from the fact that modifier alleles increasing sex escape more easily from low-fitness genetic backgrounds than alleles coding for lower rates of sex. Extrapolating the results from three-locus models to a large number of loci at mutation-selection balance indicates that in the parameter range where indirect selection is strong enough to outweigh a substantial cost of sex, interactions between selected loci have a stronger effect than the sum of individual effects of each selected locus. Comparisons with multilocus simulation results show that such extrapolations may provide correct predictions for the evolutionarily stable rate of sex, unless the cost of sex is high. © 2014 The Author. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection

PubMed Central

Cornejo, Omar E.; Durrego, Ester; Stanley, Craig E.; Castillo, Andreína I.; Herrera, Sócrates; Escalante, Ananias A.

2016-01-01

Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

Identifying the pattern of molecular evolution for Zaire ebolavirus in the 2014 outbreak in West Africa.

PubMed

Liu, Si-Qing; Deng, Cheng-Lin; Yuan, Zhi-Ming; Rayner, Simon; Zhang, Bo

2015-06-01

The current Ebola virus disease (EVD) epidemic has killed more than all previous Ebola outbreaks combined and, even as efforts appear to be bringing the outbreak under control, the threat of reemergence remains. The availability of new whole-genome sequences from West Africa in 2014 outbreak, together with those from the earlier outbreaks, provide an opportunity to investigate the genetic characteristics, the epidemiological dynamics and the evolutionary history for Zaire ebolavirus (ZEBOV). To investigate the evolutionary properties of ZEBOV in this outbreak, we examined amino acid mutations, positive selection, and evolutionary rates on the basis of 123 ZEBOV genome sequences. The estimated phylogenetic relationships within ZEBOV revealed that viral sequences from the same period or location formed a distinct cluster. The West Africa viruses probably derived from Middle Africa, consistent with results from previous studies. Analysis of the seven protein regions of ZEBOV revealed evidence of positive selection acting on the GP and L genes. Interestingly, all putatively positive-selected sites identified in the GP are located within the mucin-like domain of the solved structure of the protein, suggesting a possible role in the immune evasion properties of ZEBOV. Compared with earlier outbreaks, the evolutionary rate of GP gene was estimated to significantly accelerate in the 2014 outbreak, suggesting that more ZEBOV variants are generated for human to human transmission during this sweeping epidemic. However, a more balanced sample set and next generation sequencing datasets would help achieve a clearer understanding at the genetic level of how the virus is evolving and adapting to new conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Parallel evolution or purifying selection, not introgression, explain similarity in the pyrethroid detoxification linked GSTE4 of Anopheles gambiae and An. arabiensis

PubMed Central

Wilding, C.S.; Weetman, D.; Rippon, E.J.; Steen, K.; Mawejje, H.D.; Barsukov, I.; Donnelly, M.J.

2014-01-01

Insecticide resistance is a major impediment to the control of vectors and pests of public health importance and is a strongly selected trait capable of rapid spread, sometimes even between closely-related species. Elucidating the mechanisms generating insecticide resistance in mosquito vectors of disease, and understanding the spread of resistance within and between populations and species are vital for the development of robust resistance management strategies. Here we studied the mechanisms of resistance in two sympatric members of the Anopheles gambiae species complex – the major vector of malaria in sub-Saharan Africa – in order to understand how resistance has developed and spread in eastern Uganda, a region with some of the highest levels of malaria. In eastern Uganda, where the mosquitoes Anopheles arabiensis and An. gambiae can be found sympatrically, low levels of hybrids (0.4%) occur, offering a route for introgression of adaptively important variants between species. In independent microarray studies of insecticide resistance, Gste4, an insect-specific glutathione S-transferase, was among the most significantly up-regulated genes in both species. To test the hypothesis of interspecific introgression, we sequenced 2.3kbp encompassing Gste4. Whilst this detailed sequencing ruled out introgression, we detected strong positive selection acting on Gste4. However, these sequences, followed by haplotype-specific qPCR, showed that the apparent up-regulation in An. arabiensis is a result of allelic variation across the microarray probe binding sites which artefactually elevates the gene expression signal. Thus, face-value acceptance of microarray data can be misleading and it is advisable to conduct a more detailed investigation of the causes and nature of such signal. The identification of positive selection acting on this locus led us to functionally express and characterise allelic variants of GSTE4. Although the in vitro data do not support a direct role for GSTE4 in metabolism, they do support a role for this enzyme in insecticide sequestration. Thus, the demonstration of a role for an up-regulated gene in metabolic resistance to insecticides should not be limited to simply whether it can metabolise insecticide; such a strict criterion would argue against the involvement of GSTE4 despite the weight of evidence to the contrary. PMID:25213601

Targeting the CACNA1A IRES as a Treatment for Spinocerebellar Ataxia Type 6.

PubMed

Pastor, Parviz Daniel Hejazi; Du, Xiaofei; Fazal, Sarah; Davies, Andre N; Gomez, Christopher M

2018-02-01

We have discovered that the P/Q-type voltage-gated Ca 2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6. We performed a high-throughput screen of FDA-approved small molecules using a dual luciferase reporter system and identified ten hits able to selectively inhibit the IRES. We identified four main candidates that showed selective suppression of α1ACT relative to α1A in HEK cells expressing a native CACNA1A vector. We previously pursued another avenue of molecular intervention through miRNA silencing. We studied three human miRNAs (miRNA-711, -3191-5p, -4786) that would potentially bind to sequences within the CACNA1A IRES region, based on an miRNA prediction program. Only miRNA-3191-5p was found to selectively inhibit the translation of α1ACT in cells. We developed a hyperacute model of SCA6 in mice by injecting a pathogenic form of the IRES-mediated α1ACT (AAV9-α1ACTQ33). Finally, we tested the effectiveness of the miRNA therapy by co-expressing either control miRNA or miRNA-3191-5p and found that miRNA-3191-5p decreased the levels of α1ACTQ33 and prevented the hyperacute disease in mice. These studies provide the proof of principle that a therapy directed at selectively preventing α1ACT expression could be used to treat SCA6.

Flexible ACT & Resource-group ACT: Different Working Procedures Which Can Supplement and Strengthen Each Other. A Response.

PubMed

van Veldhuizen, Remmers; Delespaul, Philippe; Kroon, Hans; Mulder, Niels

2015-01-01

This article is a response to Nordén and Norlander's 'Absence of Positive Results for Flexible Assertive Community Treatment. What is the next approach?'[1], in which they assert that 'at present [there is] no evidence for Flexible ACT and… that RACT might be able to provide new impulses and new vitality to the treatment mode of ACT'. We question their analyses and conclusions. We clarify Flexible ACT, referring to the Flexible Assertive Community Treatment Manual (van Veldhuizen, 2013) [2] to rectify misconceptions. We discuss Nordén and Norlander's interpretation of research on Flexible ACT. The fact that too little research has been done and that there are insufficient positive results cannot serve as a reason to propagate RACT. However, the Resource Group method does provide inspiration for working with clients to involve their networks more effectively in Flexible ACT.

Genomic Porosity between Invasive Chondrostoma nasus and Endangered Endemic Parachondrostoma toxostoma (Cyprinidae): The Evolution of MHC IIB Genes

PubMed Central

Šimková, Andrea; Civáňová, Kristína; Gettová, Lenka; Gilles, André

2013-01-01

Two cyprinid species, Parachondrostoma toxostoma, an endemic threatened species, and Chondrostoma nasus, an invasive species, live in sympatry in southern France and form two sympatric zones where the presence of intergeneric hybrids is reported. To estimate the potential threat to endemic species linked to the introduction of invasive species, we focused on the DAB genes (functional MHC IIB genes) because of their adaptive significance and role in parasite resistance. More specifically, we investigated (1) the variability of MHC IIB genes, (2) the selection pattern shaping MHC polymorphism, and (3) the extent to which trans-species evolution and intergeneric hybridization affect MHC polymorphism. In sympatric areas, the native species has more diversified MHC IIB genes when compared to the invasive species, probably resulting from the different origins and dispersal of both species. A similar level of MHC polymorphism was found at population level in both species, suggesting similar mechanisms generating MHC diversity. In contrast, a higher number of DAB-like alleles per specimen were found in invasive species. Invasive species tended to express the alleles of two DAB lineages, whilst native species tended to express the alleles of only the DAB3 lineage. Hybrids have a pattern of MHC expression intermediate between both species. Whilst positive selection acting on peptide binding sites (PBS) was demonstrated in both species, a slightly higher number of positively selected sites were identified in C. nasus, which could result from parasite-mediated selection. Bayesian clustering analysis revealed a similar pattern of structuring for the genetic variation when using microsatellites or the MHC approach. We confirmed the importance of trans-species evolution for MHC polymorphism. In addition, we demonstrated bidirectional gene flow for MHC IIB genes in sympatric areas. The positive significant correlation between MHC and microsatellites suggests that demographic factors may contribute to MHC variation on a short time scale. PMID:23824831

Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.

PubMed

Troeira Henriques, Sónia; Lawrence, Nicole; Chaousis, Stephanie; Ravipati, Anjaneya S; Cheneval, Olivier; Benfield, Aurélie H; Elliott, Alysha G; Kavanagh, Angela Maria; Cooper, Matthew A; Chan, Lai Yue; Huang, Yen-Hua; Craik, David J

2017-09-15

Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development.

Brain size evolution in pipefishes and seahorses: the role of feeding ecology, life history and sexual selection.

PubMed

Tsuboi, M; Lim, A C O; Ooi, B L; Yip, M Y; Chong, V C; Ahnesjö, I; Kolm, N

2017-01-01

Brain size varies greatly at all taxonomic levels. Feeding ecology, life history and sexual selection have been proposed as key components in generating contemporary diversity in brain size across vertebrates. Analyses of brain size evolution have, however, been limited to lineages where males predominantly compete for mating and females choose mates. Here, we present the first original data set of brain sizes in pipefishes and seahorses (Syngnathidae) a group in which intense female mating competition occurs in many species. After controlling for the effect of shared ancestry and overall body size, brain size was positively correlated with relative snout length. Moreover, we found that females, on average, had 4.3% heavier brains than males and that polyandrous species demonstrated more pronounced (11.7%) female-biased brain size dimorphism. Our results suggest that adaptations for feeding on mobile prey items and sexual selection in females are important factors in brain size evolution of pipefishes and seahorses. Most importantly, our study supports the idea that sexual selection plays a major role in brain size evolution, regardless of on which sex sexual selection acts stronger. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

76 FR 16703 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... or cooperative research and development set aside for small business concerns shall be deemed an... SMALL BUSINESS ADMINISTRATION 13 CFR Parts 121, 124, 125, 126, and 127 [Docket No. SBA-2011-0006] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S...

Assessing the independent and combined effects of subsidies for antimalarials and rapid diagnostic testing on fever management decisions in the retail sector: results from a factorial randomised trial in western Kenya

PubMed Central

Prudhomme O'Meara, Wendy; Mohanan, Manoj; Laktabai, Jeremiah; Lesser, Adriane; Platt, Alyssa; Maffioli, Elisa; Turner, Elizabeth L; Menya, Diana

2016-01-01

Objectives There is an urgent need to understand how to improve targeting of artemisinin combination therapy (ACT) to patients with confirmed malaria infection, including subsidised ACTs sold over-the-counter. We hypothesised that offering an antimalarial subsidy conditional on a positive malaria rapid diagnostic test (RDT) would increase uptake of testing and improve rational use of ACTs. Methods We designed a 2×2 factorial randomised experiment evaluating 2 levels of subsidy for RDTs and ACTs. Between July 2014 and June 2015, 444 individuals with a malaria-like illness who had not sought treatment were recruited from their homes. We used scratch cards to allocate participants into 4 groups in a ratio of 1:1:1:1. Participants were eligible for an unsubsidised or fully subsidised RDT and 1 of 2 levels of ACT subsidy (current retail price or an additional subsidy conditional on a positive RDT). Treatment decisions were documented 1 week later. Our primary outcome was uptake of malaria testing. Secondary outcomes evaluated ACT consumption among those with a negative test, a positive test or no test. Results Offering a free RDT increased the probability of testing by 18.6 percentage points (adjusted probability difference (APD), 95% CI 5.9 to 31.3). An offer of a conditional ACT subsidy did not have an additional effect on the probability of malaria testing when the RDT was free (APD=2.7; 95% CI −8.6 to 14.1). However, receiving the conditional ACT subsidy increased the probability of taking an ACT following a positive RDT by 19.5 percentage points (APD, 95% CI 2.2 to 36.8). Overall, the proportion who took ACT following a negative test was lower than those who took ACT without being tested, indicated improved targeting among those who were tested. Conclusions Both subsidies improved appropriate fever management, demonstrating the impact of these costs on decision making. However, the conditional ACT subsidy did not increase testing. We conclude that each of the subsidies primarily impacts the most immediate decision. Trial registration number NCT02199977. PMID:28588946

Tribally Controlled Community Colleges Assistance Act Amendment. Hearing Before the United States Senate Select Committee on Indian Affairs, Ninety-Sixth Congress, First Session on S. 1855 to Amend Public Law 95-471, The Tribally Controlled Community Colleges Assistance Act of 1978.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

The Senate Select Committee on Indian Affairs conducted a November 26, 1979, hearing regarding proposed amendment S. 1855 to the Tribally Controlled Community Colleges Assistance Act (PL 95-471), which would increase the authorization level for technical assistance grants from $3.2 million in fiscal 1981 and 1982 to $10 million for each year. At…

Acceptance and Commitment Therapy (ACT) as a Career Counselling Strategy

ERIC Educational Resources Information Center

Hoare, P. Nancey; McIlveen, Peter; Hamilton, Nadine

2012-01-01

Acceptance and commitment therapy (ACT) has potential to contribute to career counselling. In this paper, the theoretical tenets of ACT and a selection of its counselling techniques are overviewed along with a descriptive case vignette. There is limited empirical research into ACT's application in career counselling. Accordingly, a research agenda…

15 CFR 700.8 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... approved programs. Defense Production Act. the Defense Production Act of 1950, as amended (50 U.S.C. App... its integrity as a capital item. Rated order. A prime contract, a subcontract, or a purchase order in... Service Act and related statutes—Section 18 of the Selective Service Act of 1948 (50 U.S.C. app. 468), 10...

15 CFR 700.8 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... approved programs. Defense Production Act. the Defense Production Act of 1950, as amended (50 U.S.C. App... its integrity as a capital item. Rated order. A prime contract, a subcontract, or a purchase order in... Service Act and related statutes—Section 18 of the Selective Service Act of 1948 (50 U.S.C. app. 468), 10...

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.

Relationships among grocery nutrition label users and consumers' attitudes and behavior toward restaurant menu labeling.

PubMed

Roseman, Mary G; Mathe-Soulek, Kimberly; Higgins, Joseph A

2013-12-01

In the United States (US), based on the 2010 Affordable Care Act, restaurant chains and similar retail food establishments with 20 or more locations are required to begin implementing calorie information on their menus. As enacting of the law begins, it is important to understand its potential for improving consumers' healthful behaviors. Therefore, the objective of this study was to explore relationships among users of grocery nutrition labels and attitudes toward restaurant menu labeling, along with the caloric content of their restaurant menu selection. Study participants were surveyed and then provided identical mock restaurant menus with or without calories. Results found that participants who used grocery nutrition labels and believed they would make healthy menu selections with nutrition labels on restaurant menus made healthier menu selections, regardless of whether the menu displayed calories or not. Consumers' nutrition knowledge and behaviors gained from using grocery nutrition labels and consumers' desire for restaurants to provide nutrition menu labels have a positive effect on their choosing healthful restaurant menu items. Copyright © 2013 Elsevier Ltd. All rights reserved.

Act No. 16.045 of 2 June 1989 prohibiting all discrimination that violates the principle of equality of treatment and opportunities for both sexes in all sectors of labor activity.

PubMed

1989-01-01

This Uruguayan Act prohibits discrimination in employment with respect to the following areas, among others: 1) advertising for the provision of positions; 2) selection criteria; 3) recruitment and hiring; 4) evaluation of performance criteria; 5) the right to advancement and promotion; 6) labour stability; 7) social benefits; 8) suspension and dismissal, particularly in cases involving a change of civil status, pregnancy, or nursing; 9) possibilities for professional and technical education or retraining; and 10) remuneration criteria. Reserving places for one sex because of the presence of activities in which the sex of the employee is essential for performance or to comply with international labor treaties does not constitute discrimination. Nor do compensatory acts designed to promote equality of opportunities and treatment of both sexes in concrete situations. In cases where the provisions of this Act have been violated, specially designated judges will call the parties together and may adopt measures designed to end the situation complained of. If they deem it necessary, the judges may institute more formal proceedings. If the measures adopted are not carried out, the person violating the law is subject to a daily fine, as well as administrative penalties set out in Act 15.903 of 10 November 1987. Adverse decisions may be appealed. The state is also to undertake educative campaigns to create interest in and understanding of the problems affecting women workers, thus promoting awareness in such workers and their employers of their situation.

Current spring warming as a driver of selection on reproductive timing in a wild passerine.

PubMed

Marrot, Pascal; Charmantier, Anne; Blondel, Jacques; Garant, Dany

2018-05-01

Evolutionary adaptation as a response to climate change is expected for fitness-related traits affected by climate and exhibiting genetic variance. Although the relationship between warmer spring temperature and earlier timing of reproduction is well documented, quantifications and predictions of the impact of global warming on natural selection acting on phenology in wild populations remain rare. If global warming affects fitness in a similar way across individuals within a population, or if fitness consequences are independent of phenotypic variation in key-adaptive traits, then no evolutionary response is expected for these traits. Here, we quantified the selection pressures acting on laying date during a 24-year monitoring of blue tits in southern Mediterranean France, a hot spot of climate warming. We explored the temporal fluctuation in annual selection gradients and we determined its temperature-related drivers. We first investigated the month-specific warming since 1970 in our study site and tested its influence on selection pressures, using a model averaging approach. Then, we quantified the selection strength associated with temperature anomalies experienced by the blue tit population. We found that natural selection acting on laying date significantly fluctuated both in magnitude and in sign across years. After identifying a significant warming in spring and summer, we showed that warmer daily maximum temperatures in April were significantly associated with stronger selection pressures for reproductive timing. Our results indicated an increase in the strength of selection by 46% for every +1°C anomaly. Our results confirm the general assumption that recent climate change translates into strong selection favouring earlier breeders in passerine birds. Our findings also suggest that differences in fitness among individuals varying in their breeding phenology increase with climate warming. Such climate-driven influence on the strength of directional selection acting on laying date could favour an adaptive response in this trait, since it is heritable. © 2018 The Authors. Journal of Animal Ecology © 2018 British Ecological Society.

Compliance of Postsecondary Institutions with Provisions for Disabled Students Mandated by the Architectural Barriers Act of 1968 and the Rehabilitation Act of 1973.

ERIC Educational Resources Information Center

Williams, Joan M.; Hodinko, Bernard A.

Perceptions were obtained from 480 college student services officers concerning compliance of their employing institutions with selected provisions of the Architectural Barriers Act of 1968 and the Rehabilitation Act of 1973 (specifically Section 504). The survey instrument presented a statement from each of 24 provisions of the two Acts.…

Applicants for employment who are HIV positive: a recent case.

PubMed

Du Plessis, M

2000-01-01

This paper presents a case between South African Airways (SAA) and an applicant for employment who did not volunteer information about his HIV status. The matter between Jacques Charl Hoffmann, an HIV-infected man applying for a position as flight attendant, and SAA was heard before Judge Hussain in the Witwatersrand Local Division. Mr. Hoffmann contended that SAA had unfairly discriminated against him solely on the basis of his HIV-positive status. He argued that such unfair discrimination violated his constitutional rights to dignity, equality, fair labor practices, and privacy. Considered as a whole, Judge Hussain found that the policy of SAA was justified and substantiated. It is noted that the policy is not selectively applied against those persons who are HIV-positive, instead it is directed at detecting all kinds of disabilities that make employment as a flight attendant unsuitable. To the judge, the "unsuitability" of an applicant is to be considered against the policy's consideration of "medical, safety, and operational grounds". In conclusion, the court found it justifiable for the airline to conduct medical examinations of aspiring flight attendants, and its refusal to employ Mr. Hoffmann was not an act of unfair discrimination.

SH2 Domains Recognize Contextual Peptide Sequence Information to Determine Selectivity*

PubMed Central

Liu, Bernard A.; Jablonowski, Karl; Shah, Eshana E.; Engelmann, Brett W.; Jones, Richard B.; Nash, Piers D.

2010-01-01

Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks. An examination of interactions between 50 SH2 domains and a set of 192 phosphotyrosine peptides corresponding to physiological motifs within FGF, insulin, and IGF-1 receptor pathways indicates that individual SH2 domains have distinct recognition properties and exhibit a remarkable degree of selectivity beyond that predicted by previously described binding motifs. The underlying basis for such selectivity is the ability of SH2 domains to recognize both permissive amino acid residues that enhance binding and non-permissive amino acid residues that oppose binding in the vicinity of the essential phosphotyrosine. Neighboring positions affect one another so local sequence context matters to SH2 domains. This complex linguistics allows SH2 domains to distinguish subtle differences in peptide ligands. This newly appreciated contextual dependence substantially increases the accessible information content embedded in the peptide ligands that can be effectively integrated to determine binding. This concept may serve more broadly as a paradigm for subtle recognition of physiological ligands by protein interaction domains. PMID:20627867

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2013 CFR

2013-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2014 CFR

2014-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2011 CFR

2011-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.72 - Will OSG notify Tribes/Consortia and affected non-BIA bureaus of the results of the selection...

Code of Federal Regulations, 2012 CFR

2012-04-01

... bureaus of the results of the selection process? 1000.72 Section 1000.72 Indians OFFICE OF THE ASSISTANT...-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA Programs Eligibility and Application Process § 1000.72 Will OSG...

25 CFR 1000.46 - Which Tribes/Consortia may be selected to receive a negotiation grant?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Which Tribes/Consortia may be selected to receive a negotiation grant? 1000.46 Section 1000.46 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT...

Evolution of X-degenerate Y chromosome genes in greater apes: conservation of gene content in human and gorilla, but not chimpanzee.

PubMed

Goto, Hiroki; Peng, Lei; Makova, Kateryna D

2009-02-01

Compared with the X chromosome, the mammalian Y chromosome is considerably diminished in size and has lost most of its ancestral genes during evolution. Interestingly, for the X-degenerate region on the Y chromosome, human has retained all 16 genes, while chimpanzee has lost 4 of the 16 genes since the divergence of the two species. To uncover the evolutionary forces governing ape Y chromosome degeneration, we determined the complete sequences of the coding exons and splice sites for 16 gorilla Y chromosome genes of the X-degenerate region. We discovered that all studied reading frames and splice sites were intact, and thus, this genomic region experienced no gene loss in the gorilla lineage. Higher nucleotide divergence was observed in the chimpanzee than the human lineage, particularly for genes with disruptive mutations, suggesting a lack of functional constraints for these genes in chimpanzee. Surprisingly, our results indicate that the human and gorilla orthologues of the genes disrupted in chimpanzee evolve under relaxed functional constraints and might not be essential. Taking mating patterns and effective population sizes of ape species into account, we conclude that genetic hitchhiking associated with positive selection due to sperm competition might explain the rapid decline in the Y chromosome gene number in chimpanzee. As we found no evidence of positive selection acting on the X-degenerate genes, such selection likely targets other genes on the chimpanzee Y chromosome.

32 CFR 1602.21 - Selective Service Law.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Selective Service Law. 1602.21 Section 1602.21 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM DEFINITIONS § 1602.21 Selective Service Law. The term Selective Service Law includes the Military Selective Service Act...

Classification of a large microarray data set: Algorithm comparison and analysis of drug signatures

PubMed Central

Natsoulis, Georges; El Ghaoui, Laurent; Lanckriet, Gert R.G.; Tolley, Alexander M.; Leroy, Fabrice; Dunlea, Shane; Eynon, Barrett P.; Pearson, Cecelia I.; Tugendreich, Stuart; Jarnagin, Kurt

2005-01-01

A large gene expression database has been produced that characterizes the gene expression and physiological effects of hundreds of approved and withdrawn drugs, toxicants, and biochemical standards in various organs of live rats. In order to derive useful biological knowledge from this large database, a variety of supervised classification algorithms were compared using a 597-microarray subset of the data. Our studies show that several types of linear classifiers based on Support Vector Machines (SVMs) and Logistic Regression can be used to derive readily interpretable drug signatures with high classification performance. Both methods can be tuned to produce classifiers of drug treatments in the form of short, weighted gene lists which upon analysis reveal that some of the signature genes have a positive contribution (act as “rewards” for the class-of-interest) while others have a negative contribution (act as “penalties”) to the classification decision. The combination of reward and penalty genes enhances performance by keeping the number of false positive treatments low. The results of these algorithms are combined with feature selection techniques that further reduce the length of the drug signatures, an important step towards the development of useful diagnostic biomarkers and low-cost assays. Multiple signatures with no genes in common can be generated for the same classification end-point. Comparison of these gene lists identifies biological processes characteristic of a given class. PMID:15867433

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.

H2 as a Possible Carrier of the DIBs?

NASA Astrophysics Data System (ADS)

Ubachs, W.

2014-02-01

In the 1990s the hydrogen molecule, by far the most abundant molecular species in the interstellar medium, has been proposed as a possible carrier of the diffuse interstellar bands. While some remarkable coincidences were found in the rich spectrum of inter-Rydberg transitions of this molecule with DIB-features, both in frequency position as in linewidth, some open issues remained on a required non-linear optical pumping scheme that should explain the population of certain intermediate levels and act as a selection mechanism. Recently a similar scheme has been proposed relating the occurrence of the UV-bump (the ubiquitous 2170 Å extinction feature) to the spectrum of H2, therewith reviving the H2 hypothesis.

Keeping the Show on the Road: The Role of the Acting Headteacher.

ERIC Educational Resources Information Center

Draper, Janet; McMichael, Paquita

2003-01-01

Study of acting heads' situations, experience, and support in the position. Uncertainty on length of appointment, role boundaries, and freedom to innovate led to some dissatisfaction and unwillingness to apply for permanent positions. Findings also raise issues for the maintenance of school performance in times of change and uncertainty. (Contains…

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Flexible ACT & Resource-group ACT: Different Working Procedures Which Can Supplement and Strengthen Each Other. A Response#

PubMed Central

van Veldhuizen, Remmers; Delespaul, Philippe; Kroon, Hans; Mulder, Niels

2015-01-01

This article is a response to Nordén and Norlander’s ‘Absence of Positive Results for Flexible Assertive Community Treatment. What is the next approach?’[1], in which they assert that ‘at present [there is] no evidence for Flexible ACT and… that RACT might be able to provide new impulses and new vitality to the treatment mode of ACT’. We question their analyses and conclusions. We clarify Flexible ACT, referring to the Flexible Assertive Community Treatment Manual (van Veldhuizen, 2013) [2] to rectify misconceptions. We discuss Nordén and Norlander’s interpretation of research on Flexible ACT. The fact that too little research has been done and that there are insufficient positive results cannot serve as a reason to propagate RACT. However, the Resource Group method does provide inspiration for working with clients to involve their networks more effectively in Flexible ACT. PMID:25767558

Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal

PubMed Central

Risso, Davide S.; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

2016-01-01

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes. PMID:27138342

Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.

PubMed

Risso, Davide S; Mezzavilla, Massimo; Pagani, Luca; Robino, Antonietta; Morini, Gabriella; Tofanelli, Sergio; Carrai, Maura; Campa, Daniele; Barale, Roberto; Caradonna, Fabio; Gasparini, Paolo; Luiselli, Donata; Wooding, Stephen; Drayna, Dennis

2016-05-03

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment.

PubMed

Cropley, Jennifer E; Dang, Thurston H Y; Martin, David I K; Suter, Catherine M

2012-06-22

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A(vy) mice, in which the epigenetic state of the A(vy) allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A(vy) allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations.

The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment

PubMed Central

Cropley, Jennifer E.; Dang, Thurston H. Y.; Martin, David I. K.; Suter, Catherine M.

2012-01-01

Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic Avy mice, in which the epigenetic state of the Avy allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent Avy allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations. PMID:22319121

41 CFR 301-11.11 - How do I select lodging and make lodging reservations?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Hotel and Motel Fire Safety Act of 1990 (the Act), as amended (see 5 U.S.C. 5707a). (c) When selecting a... room cancellation deadline is 4 p.m. (or later) on the day of arrival; (4) Most hotels offer last... hotel reservation call centers). The FedRooms® rate code (XVU) must be entered to get the program...

Fast-acting nuclear reactor control device

DOEpatents

Kotlyar, Oleg M.; West, Phillip B.

1993-01-01

A fast-acting nuclear reactor control device for moving and positioning a fety control rod to desired positions within the core of the reactor between a run position in which the safety control rod is outside the reactor core, and a shutdown position in which the rod is fully inserted in the reactor core. The device employs a hydraulic pump/motor, an electric gear motor, and solenoid valve to drive the safety control rod into the reactor core through the entire stroke of the safety control rod. An overrunning clutch allows the safety control rod to freely travel toward a safe position in the event of a partial drive system failure.

Career Readiness in the United States 2015. ACT Insights in Education and Work

ERIC Educational Resources Information Center

LeFebvre, Mary

2015-01-01

ACT has conducted over 20,000 job analyses for occupations across a diverse array of industries and occupations since 1993. This report highlights the levels of career readiness for various subgroups of ACT Work Keys® examinees in the United States and provides career readiness benchmarks for selected ACT WorkKeys cognitive skills by career…

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

PubMed

Romero, H; Zavala, A; Musto, H

2000-01-25

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

The ACT Vision Mission Study Simulation Effort

NASA Astrophysics Data System (ADS)

Wunderer, C. B.; Kippen, R. M.; Bloser, P. F.; Boggs, S. E.; McConnell, M. L.; Hoover, A.; Oberlack, U.; Sturner, S.; Tournear, D.; Weidenspointner, G.; Zoglauer, A.

2004-12-01

The Advanced Compton Telescope (ACT) has been selected by NASA for a one-year "Vision Mission" study. The main goal of this study is to determine feasible instrument configurations to achieve ACT's sensitivity requirements, and to give recommendations for technology development. Space-based instruments operating in the energy range of nuclear lines are subject to complex backgrounds generated by cosmic-ray interactions and diffuse gamma rays; typically measurements are significantly background-dominated. Therefore accurate, detailed simulations of the background induced in different ACT configurations, and exploration of event selection and reconstruction techniques for reducing these backgrounds, are crucial to determining both the capabilities of a given instrument configuration and the technology enhancements that would result in the most significant performance improvements. The ACT Simulation team has assembled a complete suite of tools that allows the generation of particle backgrounds for a given orbit (based on CREME96), their propagation through any instrument and spacecraft geometry (using MGGPOD) - including delayed photon emission from instrument activation - as well as the event selection and reconstruction of Compton-scatter events in the given detectors (MEGAlib). The package can deal with polarized photon beams as well as e.g. anticoincidence shields. We will report on the progress of the ACT simulation effort and the suite of tools used. We thank Elena Novikova at NRL for her contributions, and NASA for support of this research.

Evolution of stochastic demography with life history tradeoffs in density-dependent age-structured populations.

PubMed

Lande, Russell; Engen, Steinar; Sæther, Bernt-Erik

2017-10-31

We analyze the stochastic demography and evolution of a density-dependent age- (or stage-) structured population in a fluctuating environment. A positive linear combination of age classes (e.g., weighted by body mass) is assumed to act as the single variable of population size, [Formula: see text], exerting density dependence on age-specific vital rates through an increasing function of population size. The environment fluctuates in a stationary distribution with no autocorrelation. We show by analysis and simulation of age structure, under assumptions often met by vertebrate populations, that the stochastic dynamics of population size can be accurately approximated by a univariate model governed by three key demographic parameters: the intrinsic rate of increase and carrying capacity in the average environment, [Formula: see text] and [Formula: see text], and the environmental variance in population growth rate, [Formula: see text] Allowing these parameters to be genetically variable and to evolve, but assuming that a fourth parameter, [Formula: see text], measuring the nonlinearity of density dependence, remains constant, the expected evolution maximizes [Formula: see text] This shows that the magnitude of environmental stochasticity governs the classical trade-off between selection for higher [Formula: see text] versus higher [Formula: see text] However, selection also acts to decrease [Formula: see text], so the simple life-history trade-off between [Formula: see text]- and [Formula: see text]-selection may be obscured by additional trade-offs between them and [Formula: see text] Under the classical logistic model of population growth with linear density dependence ([Formula: see text]), life-history evolution in a fluctuating environment tends to maximize the average population size. Published under the PNAS license.

17 CFR 229.510 - (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities. 229.510 Section 229.510 Commodity and...-REGULATION S-K Registration Statement and Prospectus Provisions § 229.510 (Item 510) Disclosure of Commission...

17 CFR 229.510 - (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities. 229.510 Section 229.510 Commodity and...-REGULATION S-K Registration Statement and Prospectus Provisions § 229.510 (Item 510) Disclosure of Commission...

17 CFR 229.510 - (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false (Item 510) Disclosure of Commission position on indemnification for Securities Act liabilities. 229.510 Section 229.510 Commodity and...-REGULATION S-K Registration Statement and Prospectus Provisions § 229.510 (Item 510) Disclosure of Commission...

Customer emotion regulation in the service interactions: its relationship to employee ingratiation, satisfaction and loyalty intentions.

PubMed

Medler-Liraz, Hana; Yagil, Dana

2013-01-01

Many studies have explored emotional regulation on the part of service employees, and its antecedents. However, customers' emotional regulation in general, and how it is affected by service employee behavior in particular, have received only scant attention. The present article explores a model suggesting that service employees' ingratiatory behavior relates to customer emotion regulation strategies, which in turn are related to customer satisfaction and loyalty. The model was tested with 131 service employee-customer dyads. The results show that service employee ingratiation was positively related to customers' deep acting but not related to surface acting. Customers' deep acting was positively related to their satisfaction. A positive relationship was found between customer satisfaction and loyalty.

The Animal Welfare Act and the zoo: A positive approach

USGS Publications Warehouse

Olsen, Glenn H.

1989-01-01

Interpretations of the Animal Welfare Act and other regulations governing use of research animals in the United States are changing. Recent amendments to the Act have resulted in the inclusion of more species under the umbrella of regulation. The role of the zoo and wildlife veterinarian should be that of leading his or her institution into a positive endorsement of these regulations and their application. Recent additions to the Code of Federal Regulations spell out the roles of the veterinarian and the Animal Care and Use Committee at an institution.

32 CFR 1665.2 - Requests for access.

Code of Federal Regulations, 2010 CFR

2010-07-01

... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

32 CFR 1665.2 - Requests for access.

Code of Federal Regulations, 2011 CFR

2011-07-01

... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay.

PubMed

Wiggers, Helton J; Rocha, Josmar R; Fernandes, William B; Sesti-Costa, Renata; Carneiro, Zumira A; Cheleski, Juliana; da Silva, Albérico B F; Juliano, Luiz; Cezari, Maria H S; Silva, João S; McKerrow, James H; Montanari, Carlos A

2013-01-01

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i) in the low micromolar range (3-60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 µM), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.

A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit*

PubMed Central

Wang, Jingyi; Kuryatov, Alexander; Jin, Zhuang; Norleans, Jack; Kamenecka, Theodore M.; Kenny, Paul J.; Lindstrom, Jon

2015-01-01

Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs but is without effect on α3* or α6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of α4 subunits, which is also a PAM site for steroid hormone estrogens such as 17β-estradiol. Br-PBTC is much more potent than estrogens. Like 17β-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more α4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different α6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two α4 subunits but not those with only one. Three α4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs. PMID:26432642

Adjuvant treatment may benefit patients with high-risk upper rectal cancer: A nomogram and recursive partitioning analysis of 547 patients.

PubMed

Wang, Xin; Jin, Jing; Yang, Yong; Liu, Wen-Yang; Ren, Hua; Feng, Yan-Ru; Xiao, Qin; Li, Ning; Deng, Lei; Fang, Hui; Jing, Hao; Lu, Ning-Ning; Tang, Yu; Wang, Jian-Yang; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Li, Ye-Xiong

2016-10-04

The role of adjuvant chemoradiotherapy (ACRT) or adjuvant chemotherapy (ACT) in treating patients with locally advanced upper rectal cancer (URC) after total mesorectal excision (TME) surgery remains unclear. We developed a clinical nomogram and a recursive partitioning analysis (RPA)-based risk stratification system for predicting 5-year cancer-specific survival (CSS) to determine whether these individuals require ACRT or ACT. This retrospective analysis included 547 patients with primary URC. A nomogram was developed based on the Cox regression model. The performance of the model was assessed by concordance index (C-index) and calibration curve in internal validation with bootstrapping. RPA stratified patients into risk groups based on their tumor characteristics. Five independent prognostic factors (age, preoperative increased carcinoembryonic antigen and carcinoma antigen 19-9, positive lymph node [PLN] number, tumor deposit [TD], pathological T classification) were identified and entered into the predictive nomogram. The bootstrap-corrected C-index was 0.757. RPA stratification of the three prognostic groups showed obviously different prognosis. Only the high-risk group (patients with PLN ≤ 6 and TD, or PLN > 6) benefited from ACRT plus ACT when compared with surgery followed by ACRT or ACT, and surgery alone (5-year CSS: 70.8% vs. 57.8% vs. 15.6%, P < 0.001). Our nomogram predicts 5-year CSS after TME surgery for locally advanced rectal cancer and RPA-based stratification indicates that ACRT plus ACT post-surgery may be an important treatment plan with potentially ignificant survival advantages in high-risk URC. This may help to select candidates of adjuvant treatment in prospective studies.

Large-scale rainfall diversity for ACTS

NASA Technical Reports Server (NTRS)

Lin, H. P.; Vogel, Wolfhard J.

1993-01-01

From the NOAA 15 minute precipitation file for the US, data were selected for a set of 23 stations spanning a 5 year period. The selection covers the spot beam locations for ACTS and the propagation experiment sites. There is a 2 percent probability of having any simultaneous rain at 3 or more stations, but this reduces to less than 0.001 percent at a rainfall rate of 40 mm/hr.

A composite material based on nanoparticles of yttrium (III) oxide for the selective and sensitive electrochemical determination of acetaminophen.

PubMed

Baytak, Aysegul Kutluay; Teker, Tugce; Duzmen, Sehriban; Aslanoglu, Mehmet

2016-09-01

An electrochemical sensor was prepared by modifying a glassy carbon electrode (GCE) with a composite of yttrium (III) oxide nanoparticles (Y2O3NPs) and carbon nanotubes (CNTs) for the determination of acetaminophen (ACT). Compared with a bare GCE and CNTs/GCE, the Y2O3NPs/CNTs/GCE exhibited a well-defined redox couple for ACT and highly enhanced the current response. The separations in the anodic and cathodic peak potentials (ΔEp) for ACT were 552mV, 24mV and 10mV at ba4re GCE, CNTs/GCE and Y2O3NPs/CNTs/GCE, respectively. The observation of only 10mV of ΔEp for ACT at Y2O3NPs/CNTs/GCE was a clear indication of a great acceleration of the electrode process compared to bare GCE and GCE modified with CNTs. Also, l-ascorbic acid (l-AA) and l-tyrosine (l-TRY) did not interfere with the selective determination of ACT. Square wave voltammetry (SWV) was performed for the quantification of ACT. A linear plot was obtained for current responses versus the concentrations of ACT over the range from 1.0×10(-10) to 1.8×10(-8)M with a detection limit of 3.0×10(-11)M (based on 3Sb/m). The proposed composite material provided high electrocatalytic activity, improved voltammetric behavior, good selectivity and good reproducibility. The accurate quantification of ACT makes the proposed electrode of great interest for the public health. Copyright © 2016 Elsevier B.V. All rights reserved.

Recovery Act: Head Start Grantees Expand Services, but More Consistent Communication Could Improve Accountability and Decisions about Spending. Report to the Congress. GAO-11-166

ERIC Educational Resources Information Center

Ashby, Cornelia M.; Jones, Yvonne D.

2010-01-01

This report responds to two mandates for GAO under the American Recovery and Reinvestment Act of 2009 (Recovery Act). First, it is the latest report on the uses of and accountability for Recovery Act funds in selected states and localities. Second, it comments on recipients' reports of the jobs created and retained. The Recovery Act provided $2.1…

Demand for long acting contraceptive methods and associated factors among family planning service users, Northwest Ethiopia: a health facility based cross sectional study.

PubMed

Yalew, Saleamlak Adbaru; Zeleke, Berihun Megabiaw; Teferra, Alemayehu Shimeka

2015-02-04

Demand for long acting contraceptive methods is one of the key factors for total fertility rate and reproductive health issues. Increased demand for these methods can decline fertility rate through spacing and limiting family size in turn improving maternal and family health and socioeconomic development of a country. The aim of this study was to assess demand for long acting contraceptives and associated factors among family planning users in Debre-Tabor Town, Northwest Ethiopia. Facility based cross-sectional study was conducted from July to August 2013. Data was collected on 487 current family planning users through face to face interview using structured questionnaire. Study participants were selected by systematic sampling method. Data were entered in to Epi Info and analyzed by using SPSS version 20. Bi-variable and multi-variable regression analyses were done to identify factors associated with demand for long acting contraceptive methods. Odds ratio with 95% CI was used to assess the association between the independent variables and demand for long acting family planning methods. The study showed that, demand for long acting contraceptives was 17%. Only 9.2% of the women were using long acting contraceptive methods (met need). About 7.8% of women were using short acting methods while they actually want to use long acting methods (unmet need). Demand for LACMs was positively associated 3 with being a daily labour (AOR = 3.87, 95% CI = [1.06, 14.20]), being a student (AOR = 2.64, 95% CI = [1.27, 5.47]), no future birth intensions (AOR = 2.17, 95% CI = [1.12, 4.23]), having five or more children (AOR = 1.67, 95% CI = [1.58, 4.83]), deciding together with husbands for using the methods (AOR = 2.73, 95% CI = [1.40, 5.32]) and often having discussion with husband (AOR = 3.89, 95% CI = [1.98, 7.65]). Clients treated poorly by the health care providers during taking the services was negatively associated with demand for LACMs (AOR = 0.42, 95% CI = [0.24, 0.74]). Demand for long acting family planning methods was observed to be lower as compared to other studies. There were also significant proportion of women having unmet need for long acting methods - women using short acting method while actually wanting long acting methods. Therefore, it is necessary to create and increase awareness and advocacy on demand for long acting contraceptive methods considering women and their husbands. Moreover, emphasis should be given to service provision of the methods.

Evolution of Antifreeze Protein Genes in the Diatom Genus Fragilariopsis: Evidence for Horizontal Gene Transfer, Gene Duplication and Episodic Diversifying Selection

PubMed Central

Sorhannus, Ulf

2011-01-01

Hypotheses about horizontal transfer of antifreeze protein genes to ice-living diatoms were addressed using two different statistical methods available in the program Prunier. The role of diversifying selection in driving the differentiation of a set of antifreeze protein genes in the diatom genus Fragilariopsis was also investigated. Four horizontal gene transfer events were identified. Two of these took place between two major eukaryote lineages, that is from the diatom Chaetoceros neogracile to the copepod Stephos longipes and from a basidiomycete clade to a monophyletic group, consisting of the diatom species Fragilariopsis curta and Fragilariopsis cylindrus. The remaining two events included transfers from an ascomycete lineage to the proteobacterium Stigmatella aurantiaca and from the proteobacterium Polaribacter irgensii to a group composed of 4 proteobacterium species. After the Fragilariopsis lineage acquired the antifreeze protein gene from the basidiomycetes, it duplicated and went through episodic evolution, characterized by strong positive selection acting on short segments of the branches in the tree. This selection pattern suggests that the paralogs differentiated functionally over relatively short time periods. Taken together, the results obtained here indicate that the group of antifreeze protein genes considered here have a complex evolutionary history. PMID:22253534

Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode.

PubMed

Sawatzky, Edgar; Wehle, Sarah; Kling, Beata; Wendrich, Jan; Bringmann, Gerhard; Sotriffer, Christoph A; Heilmann, Jörg; Decker, Michael

2016-03-10

Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (KC = 14.3 nM) and also of hBChE (KC = 19.7 nM). The inhibitors transfer the carbamate moiety onto the active site under release of the phenolic tetrahydroquinazoline scaffolds that themselves act as neuroprotectants. By combination of kinetic data with molecular docking studies, a plausible binding model was probed describing how the tetrahydroquinazoline scaffold guides the carbamate into a close position to the active site. The model explains the influence of the carrier scaffold onto the affinity of an inhibitor just before carbamate transfer. This strategy can be used to utilize the binding mode of other carbamate-based inhibitors.

Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure—Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs

PubMed Central

Banks, Matthew L.

2017-01-01

Many cathinone analogs act as substrates or inhibitors at dopamine, norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine transporter substrates and inhibitors, such that potency at DAT > SERT is associated with high abuse potential, whereas potency at DAT < SERT is associated with low abuse potential. Quantitative structure—activity relationship (QSAR) studies with a series of 4-substituted methcathinone analogs identified volume of the 4-position substituent on the methcathinone phenyl ring as one structural determinant of both DAT vs. SERT selectivity and abuse-related behavioral effects in an intracranial self-stimulation procedure in rats. Subsequent modeling studies implicated specific amino acids in DAT and SERT that might interact with 4-substituent volume to determine effects produced by this series of cathinone analogs. These studies illustrate use of QSAR analysis to investigate pharmacology of cathinones and function of monoamine transporters. PMID:27696217

Role of functionally dominant species in varying environmental regimes: evidence for the performance-enhancing effect of biodiversity.

PubMed

Langenheder, Silke; Bulling, Mark T; Prosser, James I; Solan, Martin

2012-07-30

Theory suggests that biodiversity can act as a buffer against disturbances and environmental variability via two major mechanisms: Firstly, a stabilising effect by decreasing the temporal variance in ecosystem functioning due to compensatory processes; and secondly, a performance enhancing effect by raising the level of community response through the selection of better performing species. Empirical evidence for the stabilizing effect of biodiversity is readily available, whereas experimental confirmation of the performance-enhancing effect of biodiversity is sparse. Here, we test the effect of different environmental regimes (constant versus fluctuating temperature) on bacterial biodiversity-ecosystem functioning relations. We show that positive effects of species richness on ecosystem functioning are enhanced by stronger temperature fluctuations due to the increased performance of individual species. Our results provide evidence for the performance enhancing effect and suggest that selection towards functionally dominant species is likely to benefit the maintenance of ecosystem functioning under more variable conditions.

Quantifying selection in evolving populations using time-resolved genetic data

NASA Astrophysics Data System (ADS)

Illingworth, Christopher J. R.; Mustonen, Ville

2013-01-01

Methods which uncover the molecular basis of the adaptive evolution of a population address some important biological questions. For example, the problem of identifying genetic variants which underlie drug resistance, a question of importance for the treatment of pathogens, and of cancer, can be understood as a matter of inferring selection. One difficulty in the inference of variants under positive selection is the potential complexity of the underlying evolutionary dynamics, which may involve an interplay between several contributing processes, including mutation, recombination and genetic drift. A source of progress may be found in modern sequencing technologies, which confer an increasing ability to gather information about evolving populations, granting a window into these complex processes. One particularly interesting development is the ability to follow evolution as it happens, by whole-genome sequencing of an evolving population at multiple time points. We here discuss how to use time-resolved sequence data to draw inferences about the evolutionary dynamics of a population under study. We begin by reviewing our earlier analysis of a yeast selection experiment, in which we used a deterministic evolutionary framework to identify alleles under selection for heat tolerance, and to quantify the selection acting upon them. Considering further the use of advanced intercross lines to measure selection, we here extend this framework to cover scenarios of simultaneous recombination and selection, and of two driver alleles with multiple linked neutral, or passenger, alleles, where the driver pair evolves under an epistatic fitness landscape. We conclude by discussing the limitations of the approach presented and outlining future challenges for such methodologies.

Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes.

PubMed

Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

2014-12-22

Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. 'indicator model' and 'trade-off model'). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

PubMed

Eckert, Andrew J; Wegrzyn, Jill L; Pande, Barnaly; Jermstad, Kathleen D; Lee, Jennifer M; Liechty, John D; Tearse, Brandon R; Krutovsky, Konstantin V; Neale, David B

2009-09-01

Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular diversity in forest tree genomes. Here, we report an analysis of diversity and divergence for a set of 121 cold-hardiness candidate genes in coastal Douglas fir (Pseudotsuga menziesii var. menziesii). Application of several different tests for neutrality, including those that incorporated demographic models, revealed signatures of selection consistent with selective sweeps at three to eight loci, depending upon the severity of a bottleneck event and the method used to detect selection. Given the high levels of recombination, these candidate genes are likely to be closely linked to the target of selection if not the genes themselves. Putative homologs in Arabidopsis act primarily to stabilize the plasma membrane and protect against denaturation of proteins at freezing temperatures. These results indicate that surveys of nucleotide diversity and divergence, when framed within the context of further association mapping experiments, will come full circle with respect to their utility in the dissection of complex phenotypic traits into their genetic components.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

PubMed

Nagano, Nobuo; Tsutsui, Takaaki

2016-06-01

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

[Caffeine: a nutrient, a drug or a drug of abuse].

PubMed

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

Analysis of Corporate Average Fuel Economy (CAFE) Standards for Light Trucks and Increased Alternative Fuel Use

EIA Publications

2002-01-01

Sen. Frank Murkowski, the Ranking Minority Member of the Senate Committee on Energy and Natural Resources requested an analysis of selected portions of Senate Bill 1766 (S. 1766, the Energy Policy Act of 2002), House Resolution 4 (the Securing America's Future Energy Act of 2001) and Senate Bill 517 (S. 517, the Energy Policy Act of 2002). In response, the Energy Information Administration (EIA) has prepared a series of analyses showing the impacts of each of the selected provisions of the bills on energy supply, demand, and prices, macroeconomic variables where feasible, import dependence, and emissions.

Predicting nurses' well-being from job demands and resources: a cross-sectional study of emotional labour.

PubMed

Chou, Huei Yin; Hecker, Rob; Martin, Angela

2012-05-01

The aim of the present study was to investigate the effects of job demands and resources as well as emotional labour on job satisfaction and emotional exhaustion among nurses. While emotional labour is a construct that has considerable significance in health care as nurses often need to express organizationally desired emotions, little research has investigated the relationships between emotional labour, job demands and resources in the prediction of nurses' well-being. The questionnaire was distributed to 450 registered nurses (RN) working in a teaching hospital in Taiwan during February 2007, of which 240 valid questionnaires were returned and analysed (53.33% response rate). In addition to descriptive statistics and correlation, structural equation modelling (LISREL 8.8) was conducted. The findings showed that the frequency of interacting with difficult patients positively related to surface acting. Perceived organizational support (POS) positively related to deep acting and negatively to surface acting. The results also showed that surface acting related negatively, and deep acting related positively, to job satisfaction. The frequency of interactions with difficult patients related positively to emotional exhaustion, and negatively to job satisfaction. Perceived organizational support related negatively to emotional exhaustion and positively to job satisfaction. The results suggest that job demands, resources and emotional labour can predict nurses' well-being. The results of the present study indicate that nurses' well-being can be predicted by job demands, resources and emotional labour. There is a need to address organizational support and training programmes to enhance job satisfaction and reduce emotional exhaustion among nurses. © 2011 Blackwell Publishing Ltd.

Error analysis and assessment of unsteady forces acting on a flapping wing micro air vehicle: free flight versus wind-tunnel experimental methods.

PubMed

Caetano, J V; Percin, M; van Oudheusden, B W; Remes, B; de Wagter, C; de Croon, G C H E; de Visser, C C

2015-08-20

An accurate knowledge of the unsteady aerodynamic forces acting on a bio-inspired, flapping-wing micro air vehicle (FWMAV) is crucial in the design development and optimization cycle. Two different types of experimental approaches are often used: determination of forces from position data obtained from external optical tracking during free flight, or direct measurements of forces by attaching the FWMAV to a force transducer in a wind-tunnel. This study compares the quality of the forces obtained from both methods as applied to a 17.4 gram FWMAV capable of controlled flight. A comprehensive analysis of various error sources is performed. The effects of different factors, e.g., measurement errors, error propagation, numerical differentiation, filtering frequency selection, and structural eigenmode interference, are assessed. For the forces obtained from free flight experiments it is shown that a data acquisition frequency below 200 Hz and an accuracy in the position measurements lower than ± 0.2 mm may considerably hinder determination of the unsteady forces. In general, the force component parallel to the fuselage determined by the two methods compares well for identical flight conditions; however, a significant difference was observed for the forces along the stroke plane of the wings. This was found to originate from the restrictions applied by the clamp to the dynamic oscillations observed in free flight and from the structural resonance of the clamped FWMAV structure, which generates loads that cannot be distinguished from the external forces. Furthermore, the clamping position was found to have a pronounced influence on the eigenmodes of the structure, and this effect should be taken into account for accurate force measurements.

Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections.

PubMed

Faghih, Omeed; Zhang, Zhongsheng; Ranade, Ranae M; Gillespie, J Robert; Creason, Sharon A; Huang, Wenlin; Shibata, Sayaka; Barros-Álvarez, Ximena; Verlinde, Christophe L M J; Hol, Wim G J; Fan, Erkang; Buckner, Frederick S

2017-11-01

Antibiotic-resistant bacteria are widespread and pose a growing threat to human health. New antibiotics acting by novel mechanisms of action are needed to address this challenge. The bacterial methionyl-tRNA synthetase (MetRS) enzyme is essential for protein synthesis, and the type found in Gram-positive bacteria is substantially different from its counterpart found in the mammalian cytoplasm. Both previously published and new selective inhibitors were shown to be highly active against Gram-positive bacteria with MICs of ≤1.3 μg/ml against Staphylococcus , Enterococcus , and Streptococcus strains. Incorporation of radioactive precursors demonstrated that the mechanism of activity was due to the inhibition of protein synthesis. Little activity against Gram-negative bacteria was observed, consistent with the fact that Gram-negative bacterial species contain a different type of MetRS enzyme. The ratio of the MIC to the minimum bactericidal concentration (MBC) was consistent with a bacteriostatic mechanism. The level of protein binding of the compounds was high (>95%), and this translated to a substantial increase in MICs when the compounds were tested in the presence of serum. Despite this, the compounds were very active when they were tested in a Staphylococcus aureus murine thigh infection model. Compounds 1717 and 2144, given by oral gavage, resulted in 3- to 4-log decreases in the bacterial load compared to that in vehicle-treated mice, which was comparable to the results observed with the comparator drugs, vancomycin and linezolid. In summary, the research describes MetRS inhibitors with oral bioavailability that represent a class of compounds acting by a novel mechanism with excellent potential for clinical development. Copyright © 2017 American Society for Microbiology.

A Snapshot of Urban Adolescent Women's Contraceptive Knowledge at the Onset of a Community Long-Acting Reversible Contraceptive Promotion Initiative.

PubMed

Greenberg, Katherine Blumoff; Jenks, Sara Catherine; Piazza, Nina; Malibiran, Beatriz Ramos; Aligne, C Andrew

2017-08-01

To contextualize young women's knowledge and attitudes regarding contraception at the outset of an intervention promoting long-acting reversible contraceptive (LARC) use for teen pregnancy prevention. Our intervention was on the basis of diffusion of innovation theory, and at the outset we were interested in likely early adopters' existing knowledge and attitudes toward contraception. This mixed methods study consisted of focus groups within positive youth development programs in Rochester, New York; we discussed young women's knowledge and sources of information for all US Food and Drug Administration-approved contraceptive methods. Seven focus groups and 24 female adolescent participants aged 15-19 years. Quantitative ranking of all contraceptive methods; qualitative themes from focus group discussions. Our findings showed a high level of knowledge about a select group of methods, which included LARC methods, and that participants received contraceptive information from peers and family. Participants had more concerns than positive impressions regarding the effectiveness, safety, practicality, and partner reception of the contraceptive methods, with the exception of the condom. Quantitatively, the condom received the highest average rating. The importance of personal anecdotes in our findings supports the use of outreach and information campaigns; providing medically accurate information and spreading positive personal anecdotes will be key to improving young women's impressions of the safety and acceptability of LARC use. This snapshot of contraceptive knowledge indicates that young women can be mature, informed consumers of sexual and reproductive health care, and through diffusion of innovation could be key players in promoting the most effective means of pregnancy prevention. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The Patient Protection and Affordable Care Act: The Role of the School Nurse. Position Statement

ERIC Educational Resources Information Center

Combe, Laurie G.; Sharpe, Susan; Feeser, Cynthia Jo; Ondeck, Lynnette; Fekaris, Nina

2015-01-01

It is the position of the National Association of School Nurses (NASN) that the registered professional school nurse (hereinafter referred to as school nurse) serves a vital role in the delivery of health care to our nation's students within the healthcare system reshaped by the Patient Protection and Affordable Care Act of 2010, commonly known as…

Perceiving and acting upon spaces in a VR rugby task: expertise effects in affordance detection and task achievement.

PubMed

Correia, Vanda; Araújo, Duarte; Cummins, Alan; Craig, Cathy M

2012-06-01

This study used a virtual, simulated 3 vs. 3 rugby task to investigate whether gaps opening in particular running channels promote different actions by the ball carrier player and whether an effect of rugby expertise is verified. We manipulated emergent gaps in three different locations: Gap 1 in the participant's own running channel, Gap 2 in the first receiver's running channel, and Gap 3 in the second receiver's running channel. Recreational, intermediate, professional, and nonrugby players performed the task. They could (i) run with the ball, (ii) make a short pass, or (iii) make a long pass. All actions were digitally recorded. Results revealed that the emergence of gaps in the defensive line with respect to the participant's own position significantly influenced action selection. Namely, "run" was most often the action performed in Gap 1, "short pass" in Gap 2, and "long pass" in Gap 3 trials. Furthermore, a strong positive relationship between expertise and task achievement was found.

Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases.

PubMed

Eichmann, Thomas O; Kumari, Manju; Haas, Joel T; Farese, Robert V; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf

2012-11-30

Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. The selectivity of ATGL broadens to the sn-1 position upon stimulation of the enzyme by its co-activator CGI-58. sn-1,3 DAG is the preferred substrate for the consecutive hydrolysis by hormone-sensitive lipase. Interestingly, diacylglycerol-O-acyltransferase 2, present at the endoplasmic reticulum and on lipid droplets, preferentially esterifies sn-1,3 DAG. This suggests that ATGL and diacylglycerol-O-acyltransferase 2 act coordinately in the hydrolysis/re-esterification cycle of TAGs on lipid droplets. Because ATGL preferentially generates sn-1,3 and sn-2,3, it suggests that TAG-derived DAG cannot directly enter phospholipid synthesis or activate protein kinase C without prior isomerization.

Chaotic carrier pulse position modulation communication system and method

DOEpatents

Abarbanel, Henry D. I.; Larson, Lawrence E.; Rulkov, Nikolai F.; Sushchik, Mikhail M.; Tsimring, Lev S.; Volkovskii, Alexander R.

2001-01-01

A chaotic carrier pulse position modulation communication system and method is disclosed. The system includes a transmitter and receiver having matched chaotic pulse regenerators. The chaotic pulse regenerator in the receiver produces a synchronized replica of a chaotic pulse train generated by the regenerator in the transmitter. The pulse train from the transmitter can therefore act as a carrier signal. Data is encoded by the transmitter through selectively altering the interpulse timing between pulses in the chaotic pulse train. The altered pulse train is transmitted as a pulse signal. The receiver can detect whether a particular interpulse interval in the pulse signal has been altered by reference to the synchronized replica it generates, and can therefore detect the data transmitted by the receiver. Preferably, the receiver predicts the earliest moment in time it can expect a next pulse after observation of at least two consecutive pulses. It then decodes the pulse signal beginning at a short time before expected arrival of a pulse.

Multiple-Line Inference of Selection on Quantitative Traits

PubMed Central

Riedel, Nico; Khatri, Bhavin S.; Lässig, Michael; Berg, Johannes

2015-01-01

Trait differences between species may be attributable to natural selection. However, quantifying the strength of evidence for selection acting on a particular trait is a difficult task. Here we develop a population genetics test for selection acting on a quantitative trait that is based on multiple-line crosses. We show that using multiple lines increases both the power and the scope of selection inferences. First, a test based on three or more lines detects selection with strongly increased statistical significance, and we show explicitly how the sensitivity of the test depends on the number of lines. Second, a multiple-line test can distinguish between different lineage-specific selection scenarios. Our analytical results are complemented by extensive numerical simulations. We then apply the multiple-line test to QTL data on floral character traits in plant species of the Mimulus genus and on photoperiodic traits in different maize strains, where we find a signature of lineage-specific selection not seen in two-line tests. PMID:26139839

The inferior parietal lobule: where action becomes perception.

PubMed

Rizzolatti, Giacomo; Ferrari, Pier Francesco; Rozzi, Stefano; Fogassi, Leonardo

2006-01-01

The view defended in this article is that action and perception share the same neural substrate. To substantiate this view, the anatomical and functional organization of the inferior parietal lobule (IPL) is reviewed. In particular, it will be shown that many IPL neurons discharge selectively when the monkey executes a given motor act (e.g. grasping). Most interestingly, most of them fire only if the coded motor act is followed by a subsequent specific motor act (e.g. placing). Some of these action-constrained motor neurons have mirror properties and selectively discharge during the observation of motor acts when these are embedded in a given action (e.g. grasping for eating, but not grasping for placing). Thus, the activation of these IPL neurons allows the observer not only to recognize the observed motor act, but also to predict what will be the next motor act of the action, that is to understand the intentions of the action's agent. The finding that the same neurons that are active during the execution of specific motor acts also mediate the understanding of the 'what' and the 'why' of others' actions provides strong evidence for a common neural substrate for action and perception.

Effects of Lewis acidity of metal oxide promoters on the activity and selectivity of Co-based Fischer–Tropsch synthesis catalysts

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

Johnson, Gregory R.; Bell, Alexis T.

2016-06-17

Metal oxides of Ce, Gd, La, Mn, and Zr were investigated as promoters for improving the activity and selectivity of Co-based FTS catalysts. The extent to which these promoters decrease the selectivity toward CH 4 and increase the selectivity toward C 5+ hydrocarbons was found to depend on both the loading and the composition of the oxide promoter. Elemental mapping by STEM–EDS revealed that the propensity for a given metal oxide to associate with Co affects the sensitivity of the product distribution to changes in promoter loading. For all promoters, a sufficiently high loading resulted in the product distributions becomingmore » insensitive to further increases in promoter loading, very likely due to the formation of a half monolayer of promoter oxide over the Co surface. Simulations suggest that the fraction of Co active sites that are adjacent to the promoter moieties approaches unity at this degree of coverage. The oxidation state of the promoter metal cation under reaction conditions, determined by in situ XANES measurements, was used to calculate relative Lewis acidity of the promoter metal cation. A strong positive correlation was found between the C 5+ product selectivity and the Lewis acidity of the promoter metal cations, suggesting that the promotional effects are a consequence of Lewis acid–base interactions between the reaction intermediates and the promoter metal cations. Rate data obtained at different pressures were used to estimate the apparent rate coefficient and the CO adsorption constant appearing in the Langmuir–Hinshelwood expression that describes the CO consumption kinetics for both unpromoted and the metal oxide-promoted catalysts. Both parameters exhibited positive correlations with the promoter Lewis acidity. In conclusion, these results are consistent with the hypothesis that the metal cations of the promoter act as Lewis acids that interact with the O atom of adsorbed CO to facilitate CO adsorption and dissociation.« less

Effects of Lewis acidity of metal oxide promoters on the activity and selectivity of Co-based Fischer–Tropsch synthesis catalysts

DOE PAGES

Johnson, Gregory R.; Bell, Alexis T.

2016-03-31

Metal oxides of Ce, Gd, La, Mn, and Zr were investigated as promoters for improving the activity and selectivity of Co-based FTS catalysts. The extent to which these promoters decrease the selectivity toward CH 4 and increase the selectivity toward C 5+ hydrocarbons was found to depend on both the loading and the composition of the oxide promoter. Elemental mapping by STEM-EDS revealed that the propensity for a given metal oxide to associate with Co affects the sensitivity of the product distribution to changes in promoter loading. For all promoters, a sufficiently high loading resulted in the product distributions becomingmore » insensitive to further increases in promoter loading, very likely due to the formation of a half monolayer of promoter oxide over the Co surface. Simulations suggest that the fraction of Co active sites that are adjacent to the promoter moieties approaches unity at this degree of coverage. The oxidation state of the promoter metal cation under reaction conditions, determined by in situ XANES measurements, was used to calculate relative Lewis acidity of the promoter metal cation. We found a strong positive correlation between the C 5+ product selectivity and the Lewis acidity of the promoter metal cations, suggesting that the promotional effects are a consequence of Lewis acid-base interactions between the reaction intermediates and the promoter metal cations. Rate data obtained at different pressures were used to estimate the apparent rate coefficient and the CO adsorption constant appearing in the Langmuir-Hinshelwood expression that describes the CO consumption kinetics for both unpromoted and the metal oxide-promoted catalysts. Both parameters exhibited positive correlations with the promoter Lewis acidity. Our results are consistent with the hypothesis that the metal cations of the promoter act as Lewis acids that interact with the O atom of adsorbed CO to facilitate CO adsorption and dissociation.« less

Stumpage price projections for selected Western species.

Treesearch

Richard W. Haynes; Kent P. Connaughton; Darius M. Adams

1980-01-01

The 1980 Resources Planning Act Timber Assessment and Program prepared in response to provisions of the Forest and Rangeland Renewable Resources Planning Act of 1974 (as amended by the National Forest Management Act of 1976) contains regional projections of average stumpage prices that are potentially useful in national forest planning. Their usefulness can be improved...

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... given that on December 29, 2011, a proposed consent decree in United States, et al. v. Essroc Cement... statutory and regulatory requirements of the Clean Air Act (the ``Act'') at Essroc cement plants: the... X at five cement kilns. The proposed consent decree also requires testing a selective catalytic...

75 FR 50773 - Invocation of Sunken Military Craft Act

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2010-08-17

... approximately 2450 ft of water near position: 32-58.0 N 118-10.10 W. This location now serves as the gravesite... under the Sunken Military Craft Act (10 U.S.C. 113 note; Pub. L. 108-375, Sections 1401-1408) (``the Act...

76 FR 44057 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... SECURITIES AND EXCHANGE COMMISSION Sunshine Act Meeting Notice is hereby given, pursuant to the provisions of the Government in the Sunshine Act, Public Law 94-409, that the Securities and Exchange... (DTC). DTC operates an automated, centralized system for book-entry movement of securities positions in...

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study, volume 1

NASA Technical Reports Server (NTRS)

Hanks, G. W.; Shomber, H. A.; Dethman, H. A.; Gratzer, L. B.; Maeshiro, A.; Gangsaas, D.; Blight, J. D.; Buchan, S. M.; Crumb, C. B.; Dorwart, R. J.

1981-01-01

An active controls technology (ACT) system architecture was selected based on current technology system elements and optimal control theory was evaluated for use in analyzing and synthesizing ACT multiple control laws. The system selected employs three redundant computers to implement all of the ACT functions, four redundant smaller computers to implement the crucial pitch-augmented stability function, and a separate maintenance and display computer. The reliability objective of probability of crucial function failure of less than 1 x 10 to the -9th power per flight of 1 hr can be met with current technology system components, if the software is assumed fault free and coverage approaching 1.0 can be provided. The optimal control theory approach to ACT control law synthesis yielded comparable control law performance much more systematically and directly than the classical s-domain approach. The ACT control law performance, although somewhat degraded by the inclusion of representative nonlinearities, remained quite effective. Certain high-frequency gust-load alleviation functions may require increased surface rate capability.

Moral identity and the experience of moral elevation in response to acts of uncommon goodness.

PubMed

Aquino, Karl; McFerran, Brent; Laven, Marjorie

2011-04-01

Four studies using survey and experimental designs examined whether people whose moral identity is highly self-defining are more susceptible to experiencing a state of moral elevation after being exposed to acts of uncommon moral goodness. Moral elevation consists of a suite of responses that motivate prosocial action tendencies. Study 1 showed that people higher (vs. lower) in moral identity centrality reported experiencing more intense elevating emotions, had more positive views of humanity, and were more desirous of becoming a better person after reading about an act of uncommon goodness than about a merely positive situation or an act of common benevolence. Study 2 showed that those high in moral identity centrality were more likely to recall acts of moral goodness and experience moral elevation in response to such events more strongly. These experiences were positively related to self-reported prosocial behavior. Study 3 showed a direct effect on behavior using manipulated, rather than measured, moral identity centrality. Study 4 replicated the effect of moral identity on the states of elevation as well as on self-reported physical sensations and showed that the elevation mediates the relationship between moral identity, witnessing uncommon goodness, and prosocial behavior.

78 FR 32257 - Privacy Act of 1974; Report of a New Routine Use for Selected CMS Systems of Records

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2013-05-29

... systems of records to assist in preventing and detecting fraud, waste and abuse. The new routine use will... for the purpose of preventing and detecting fraud, waste and abuse, pursuant to section 1128C(a)(2) of the Social Security Act (``the Act''). At section 1128C(c) of the Act, a health plan is defined as a...

Validating Standardized Testing: The Role of the SAT and ACT in Undergraduate Admissions. [Hearing before the California Legislature, Senate Select Committee on Higher Education Admissions and Outreach, Sacramento, California, February 5, 1998].

ERIC Educational Resources Information Center

California State Legislature, Sacramento. Senate Select Committee on Higher Education Admissions and Outreach.

This report contains testimony and materials presented at the California Senate Select Committee on Higher Education Admissions and Outreach hearing, February 1998, held to examine the role of the Scholastic Assessment Test (SAT) and the American College Test (ACT) in undergraduate admissions to the public universities of California. In her…

Intraspecific divergence in sperm morphology of the green sea urchin, Strongylocentrotus droebachiensis: implications for selection in broadcast spawners

PubMed Central

2008-01-01

Background Sperm morphology can be highly variable among species, but less is known about patterns of population differentiation within species. Most studies of sperm morphometric variation are done in species with internal fertilization, where sexual selection can be mediated by complex mating behavior and the environment of the female reproductive tract. Far less is known about patterns of sperm evolution in broadcast spawners, where reproductive dynamics are largely carried out at the gametic level. We investigated variation in sperm morphology of a broadcast spawner, the green sea urchin (Strongylocentrotus droebachiensis), within and among spawnings of an individual, among individuals within a population, and among populations. We also examined population-level variation between two reproductive seasons for one population. We then compared among-population quantitative genetic divergence (QST) for sperm characters to divergence at neutral microsatellite markers (FST). Results All sperm traits except total length showed strong patterns of high diversity among populations, as did overall sperm morphology quantified using multivariate analysis. We also found significant differences in almost all traits among individuals in all populations. Head length, axoneme length, and total length had high within-male repeatability across multiple spawnings. Only sperm head width had significant within-population variation across two reproductive seasons. We found signatures of directional selection on head length and head width, with strong selection possibly acting on head length between the Pacific and West Atlantic populations. We also discuss the strengths and limitations of the QST-FST comparison. Conclusion Sperm morphology in S. droebachiensis is highly variable, both among populations and among individuals within populations, and has low variation within an individual across multiple spawnings. Selective pressures acting among populations may differ from those acting within, with directional selection implicated in driving divergence among populations and balancing selection as a possible mechanism for producing variability among males. Sexual selection in broadcast spawners may be mediated by different processes from those acting on internal fertilizers. Selective divergence in sperm head length among populations is associated with ecological differences among populations that may play a large role in mediating sexual selection in this broadcast spawner. PMID:18851755

Repeated divergent selection on pigmentation genes in a rapid finch radiation

PubMed Central

Campagna, Leonardo; Repenning, Márcio; Silveira, Luís Fábio; Fontana, Carla Suertegaray; Tubaro, Pablo L.; Lovette, Irby J.

2017-01-01

Instances of recent and rapid speciation are suitable for associating phenotypes with their causal genotypes, especially if gene flow homogenizes areas of the genome that are not under divergent selection. We study a rapid radiation of nine sympatric bird species known as capuchino seedeaters, which are differentiated in sexually selected characters of male plumage and song. We sequenced the genomes of a phenotypically diverse set of species to search for differentiated genomic regions. Capuchinos show differences in a small proportion of their genomes, yet selection has acted independently on the same targets in different members of this radiation. Many divergent regions contain genes involved in the melanogenesis pathway, with the strongest signal originating from putative regulatory regions. Selection has acted on these same genomic regions in different lineages, likely shaping the evolution of cis-regulatory elements, which control how more conserved genes are expressed and thereby generate diversity in classically sexually selected traits. PMID:28560331

76 FR 62412 - Agency Forms Undergoing Paperwork Reduction Act Review

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2011-10-07

... for Registration, (2) Request to Transfer Select Agent or Toxin, (3) Report of Theft, Loss, or Release..., or Release of Select Agent and Toxin, (4) Report of Identification of Select Agent or Toxin. There... Release of Select Agent or Toxin; (4) Report of Identification of Select Agent or Toxin; and (5) Request...

Sewall Wright, shifting balance theory, and the hardening of the modern synthesis.

PubMed

Ishida, Yoichi

2017-02-01

The period between the 1940s and 1960s saw the hardening of the modern synthesis in evolutionary biology. Gould and Provine argue that Wright's shifting balance theory of evolution hardened during this period. But their account does not do justice to Wright, who always regarded selection as acting together with drift. This paper presents a more adequate account of the development of Wright's shifting balance theory, paying particular attention to his application of the theory to the geographical distribution of flower color dimorphism in Linanthus parryae. The account shows that even in the heyday of the hardened synthesis, the balance or interaction of evolutionary factors, such as drift, selection, and migration, occupied pride of place in Wright's theory, and that between the 1940s and 1970s, Wright developed the theory of isolation by distance to quantitatively represent the structure of the Linanthus population, which he argued had the kind of structure posited by his shifting balance theory. In the end, Wright arrived at a sophisticated description of the structure of the Linanthus population, where the interaction between drift and selection varied spatially. Copyright © 2016 Elsevier Ltd. All rights reserved.

Re-visioning evidence: Reflections on the recent controversy around gender selective abortion in the UK.

PubMed

Unnithan, Maya; Dubuc, Sylvie

2018-06-01

Reports in the British media over the last 4 years have highlighted the schisms and contestations that have accompanied the reports of gender selective abortions amongst British Asian families. The position that sex-selection may be within the terms of the 1967 Abortion Act has particularly sparked controversy amongst abortion campaigners and politicians but equally among medical practitioners and the British Pregnancy Advisory Service who have hitherto tended to stay clear of such debates. In what ways has the controversy around gender-based abortion led to new framings of the entitlement to service provision and new ways of thinking about evidence in the context of reproductive rights? We reflect on these issues drawing on critiques of what constitutes best evidence, contested notions of reproductive rights and reproductive governance, comparative work in India and China as well as our involvement with different groups of campaigners including British South Asian NGOs. The aim of the paper is to situate the medical and legal provision of abortion services in Britain within current discursive practices around gender equality, ethnicity, reproductive autonomy, probable and plausible evidence, and policies of health reform.

Habitat stability, predation risk and 'memory syndromes'.

PubMed

Dalesman, S; Rendle, A; Dall, S R X

2015-05-27

Habitat stability and predation pressure are thought to be major drivers in the evolutionary maintenance of behavioural syndromes, with trait covariance only occurring within specific habitats. However, animals also exhibit behavioural plasticity, often through memory formation. Memory formation across traits may be linked, with covariance in memory traits (memory syndromes) selected under particular environmental conditions. This study tests whether the pond snail, Lymnaea stagnalis, demonstrates consistency among memory traits ('memory syndrome') related to threat avoidance and foraging. We used eight populations originating from three different habitat types: i) laboratory populations (stable habitat, predator-free); ii) river populations (fairly stable habitat, fish predation); and iii) ditch populations (unstable habitat, invertebrate predation). At a population level, there was a negative relationship between memories related to threat avoidance and food selectivity, but no consistency within habitat type. At an individual level, covariance between memory traits was dependent on habitat. Laboratory populations showed no covariance among memory traits, whereas river populations showed a positive correlation between food memories, and ditch populations demonstrated a negative relationship between threat memory and food memories. Therefore, selection pressures among habitats appear to act independently on memory trait covariation at an individual level and the average response within a population.

Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy.

PubMed

Koukouikila-Koussounda, Felix; Jeyaraj, Sankarganesh; Nguetse, Christian N; Nkonganyi, Charles Nchotebah; Kokou, Kossiwa Clarisse; Etoka-Beka, Mandingha K; Ntoumi, Francine; Velavan, Thirumalaisamy P

2017-04-19

Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. Blood samples of 431 febrile children aged 1-10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All samples were screened for malaria parasites using nested PCR. Direct sequencing was used to determine the frequency distribution of genetic variants in the anti-malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6, Pfk13) in malaria-positive isolates. One-hundred and nineteen (N = 70 from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A relative decrease in the proportion of chloroquine-resistant haplotype (CVIET) from 100% in 2005, 1 year before the introduction and implementation of ACT in 2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug transporter gene, a considerable reduction in the frequency of the mutations N86Y (from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015). Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced to null in 2015. None of the parasites harboured the Pfk13 mutations associated with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new Pfk13 variants are reported among the investigated isolates. The implementation of ACT has led to the decline in prevalence of chloroquine-resistant parasites in the Republic of Congo. However, the constant prevalence of the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate a selective drug pressure still exists. Taken together, this study could serve as the basis for epidemiological studies monitoring the distribution of molecular markers of artemisinin resistance in the Republic of Congo.

Healthy individuals treated with clomipramine: an fMRI study of brain activity during autobiographical recall of emotions.

PubMed

Cerqueira, C T; Sato, J R; de Almeida, J R C; Amaro, E; Leite, C C; Gorenstein, C; Gentil, V; Busatto, G F

2014-07-01

Various functional magnetic resonance imaging studies addressed the effects of antidepressant drugs on brain functioning in healthy subjects; however, none specifically investigated positive mood changes to antidepressant drug. Sixteen subjects with no personal or family history of psychiatric disorders were selected from an ongoing 4-week open trial of small doses of clomipramine. Follow-up interviews documented clear positive treatment effects in six subjects, with reduced irritability and tension in social interactions, improved decision making, higher self-confidence and brighter mood. These subjects were then included in a placebo-controlled confirmatory trial and were scanned immediately after 4 weeks of clomipramine use and again 4 weeks after the last dose of clomipramine. The functional magnetic resonance imaging (fMRI) scans were run during emotion-eliciting stimuli. Repeated-measures analysis of variance of brain activity patterns showed significant interactions between group and treatment status during induced irritability (P<0.005 cluster-based) but not during happiness. Individuals displaying a positive subjective response do clomipramine had higher frontoparietal cortex activity during irritability than during happiness and neutral emotion, and higher temporo-parieto-occipital cortex activity during irritability than during happiness. We conclude that antidepressants not only induce positive mood responses but also act upon autobiographical recall of negative emotions.

36 CFR 72.56 - Grant program compliance requirements.

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2010-07-01

... INTERIOR URBAN PARK AND RECREATION RECOVERY ACT OF 1978 Grant Selection, Approval and Administration § 72... Order 12185, Conservation of Petroleum and Natural Gas Flood Disaster Protection Act of 1973 (Pub. L. 93...

36 CFR 72.56 - Grant program compliance requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... INTERIOR URBAN PARK AND RECREATION RECOVERY ACT OF 1978 Grant Selection, Approval and Administration § 72... Order 12185, Conservation of Petroleum and Natural Gas Flood Disaster Protection Act of 1973 (Pub. L. 93...

Necessary Relief: The Stewart B. McKinney Homeless Assistance Act.

ERIC Educational Resources Information Center

Akins, Julie

Despite the positive contributions of the 1987 Stewart B. McKinney Homeless Assistance Act (the McKinney Act), Federal emergency aid has failed to keep pace with the growing need for assistance. Less than one year after the passage of the McKinney Act, progress has been made toward meeting the emergency need for food, shelter, and health care…

Duplication and selection in the evolution of primate β-defensin genes

PubMed Central

Semple, Colin AM; Rolfe, Mark; Dorin, Julia R

2003-01-01

Background Innate immunity is the first line of defense against microorganisms in vertebrates and acts by providing an initial barrier to microorganisms and triggering adaptive immune responses. Peptides such as β-defensins are an important component of this defense, providing a broad spectrum of antimicrobial activity against bacteria, fungi, mycobacteria and several enveloped viruses. β-defensins are small cationic peptides that vary in their expression patterns and spectrum of pathogen specificity. Disruptions in β-defensin function have been implicated in human diseases, including cystic fibrosis, and a fuller understanding of the variety, function and evolution of human β-defensins might form the basis for novel therapies. Here we use a combination of laboratory and computational techniques to characterize the main human β-defensin locus on chromosome 8p22-p23. Results In addition to known genes in the region we report the genomic structures and expression patterns of four novel human β-defensin genes and a related pseudogene. These genes show an unusual pattern of evolution, with rapid divergence between second exon sequences that encode the mature β-defensin peptides matched by relative stasis in first exons that encode signal peptides. Conclusions We conclude that the 8p22-p23 locus has evolved by successive rounds of duplication followed by substantial divergence involving positive selection, to produce a diverse cluster of paralogous genes established before the human-baboon divergence more than 23 million years ago. Positive selection, disproportionately favoring alterations in the charge of amino-acid residues, is implicated as driving second exon divergence in these genes. PMID:12734011

Family protective factors among urban African American youth.

PubMed

McCabe, K M; Clark, R; Barnett, D

1999-06-01

Examined the relations among family protective factors, stressful events, and behavioral adjustment of 64 African American 6th graders. The youths reported on family stressors, father-figure involvement, and kin support. Their primary caregivers reported on parenting, father-figure involvement, and family stressors. Teachers reported on child social skill deficits, acting out, and shy or anxious behavior. Based on regression analyses, stress exposure associated positively with child social skill deficits, acting out, and shy or anxious behavior. Parental warmth was associated negatively with shy or anxious behavior. Parental use of corporal punishment was associated positively with child acting out. For youth exposed to high numbers of family stressors, parental demandingness was associated negatively with child acting out and kin support was associated negatively with acting out and shy or anxious behavior, suggesting that these family factors partially shield children from the negative effects of stress.

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

Sortase A Inhibitors: Recent Advances and Future Perspectives.

PubMed

Cascioferro, Stella; Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Schillaci, Domenico; Daidone, Giuseppe

2015-12-10

Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans.

Impact of patient outcomes and cost aspects on reimbursement recommendations in Poland in 2012-2014.

PubMed

Malinowski, Krzysztof Piotr; Kawalec, Paweł; Trąbka, Wojciech

2016-11-01

The aim of this study was to assess the influence of different factors on the final reimbursement recommendations for drugs in Poland and to identify the correlation between these factors and the probability of a positive reimbursement recommendation for an applicant drug issued by the President of the Agency for Health Technology Assessment and Tariff System (AOTMiT). We analysed all recommendations for the period of 2012-2014 in Poland, three years following the launch of the new Reimbursement Act of Medicines, Foodstuffs Intended for Particular Nutritional Uses and Medical Devices. For each recommendation we collected data on efficacy, safety, cost of therapy, cost-effectiveness, quality of evidence, orphan drug status and others. Logistic regression was used to identify factors that increase the odds of a positive reimbursement recommendation. We analysed 221 recommendations for drugs, of which 78% were positive. We observed significant associations of all selected factors with positive recommendations. Proven efficacy and safety were associated with much greater odds for a positive reimbursement recommendation (123.5 and 42.6, respectively) than cost factors, which may suggest that patient outcome is much more important than the results of the cost-effectiveness analysis (odds ratio of 3.5) and the general cost of therapy (odds ratio of 3) in the analysed period. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An exploratory analysis of contraceptive method choice and symptoms of depression in adolescent females initiating prescription contraception.

PubMed

Francis, Jenny; Presser, Liandra; Malbon, Katherine; Braun-Courville, Debra; Linares, Lourdes Oriana

2015-04-01

We examine the association between depressive symptoms and contraceptive method choice among adolescents initiating prescription contraception. This cross-sectional study analyzes baseline data of 220 urban, minority adolescent females (ages 15-19 years) presenting for prescription contraceptive initiation at a comprehensive, free-of-cost, adolescent health center in New York City. All participants met with a health care provider who provided standard contraception counseling before initiating contraception. Each participant then selected a short- or long-acting contraceptive: a 3-month supply of the pill, patch, ring or a medroxyprogesterone acetate depot injection (short-acting), or placement/referral for an intrauterine device (IUD; long-acting). We assess the independent association between contraceptive method selection and symptoms of depression [assessed by the Center for Epidemiological Studies - Depression (CES-D) scale]. Ten percent (n=21/220) of adolescent females selected an IUD. Bivariate analysis revealed that those with elevated levels of depressive symptoms were more likely to select an IUD as compared to those with minimal symptoms (mean CES-D score 20 vs. 13; t=3.052, p=.003). In multivariate logistic regressions, adolescent females had increased odds of selecting an IUD if they reported moderate to severe depressive symptoms (adjusted odds ratio=4.93; confidence interval, 1.53-15.83; p=.007) after controlling for ethnicity/race, education, number of lifetime partners and gravidity. Inner-city, minority adolescents with elevated symptoms of depression who present for prescription contraceptive initiation may be more likely to select an IUD rather than shorter-acting methods. By recognizing adolescent females with depressive symptoms, providers can strategize their approach to effective contraception counseling. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Comparison of 4-Layer Bandages and an Adaptive Compression Therapy Device on Intended Pressure Delivery.

PubMed

Mayrovitz, Harvey N; Partsch, Hugo; Vanscheidt, Wolfgang

2015-01-01

To characterize and compare interface pressure profiles of an adaptive compression therapy (ACT) device and a traditional 4-layer bandage (4LB) system. A prospective, randomized, open-label, 1-arm, active controlled study. The sample comprised 12 healthy volunteers. Subjects wore both devices for 8 hours on 3 consecutive days. Treatments were randomized to left and right legs. One clinician performed all applications and was experienced in the clinical use of both devices. Pressures were measured in seated and standing positions at the lower, mid, and upper calf immediately post application and after 1, 4, and 8 hours. Pressures achieved with the ACT were closer to targeted 40/30/20 mmHg graduated pressure values and were significantly less than the 4LB for corresponding sites/postures (P < .001). In the seated position, initial interface pressures (mean ± SD) for the ACT were 36.9 ± 4.9, 30.5 ± 4.5, and 21.0 ± 3.6 mmHg. Corresponding interface pressures for the 4LB were 52.5 ± 8.4, 57.5 ± 10.3, and 53.5 ± 12.9 mmHg. In the standing position, initial interface pressures for the ACT were 40.7 ± 4.8, 35.6 ± 4.5, and 21.1 ± 4.6 compared to 54.6 ± 12.5, 64.4 ± 10.9, and 53.7 ± 14.3 for the 4LB. At 1, 4, and 8 hours after application, the 4LB showed a significant progressive decline in interface pressure in both seated and standing positions (P < .001). Conversely, the ACT did not decrease over time and there was a slight but significant increase for lower and mid-calf sites in the seated position (P < .001). The ACT device provided more consistent interface pressures than the 4LB and the pressures achieved were consistent with contemporary venous ulcer therapy standards.

Parent Experiences in Using Positive Behavior Support to Reduce Challenging Behavior in Children with Severe Disabilities: A Qualitative Case Study

ERIC Educational Resources Information Center

Thomas, C. Adrainne

2010-01-01

In the 1970s, the Education for the Handicapped Act (EAHCA) gave rights to parents to receive training and mandated that schools provide it. The 1997, Individuals with Disabilities Act (IDEA 1997) mandated the use of PBS for children with problem behaviors. IDEA 1997 required that schools create behavior plans with positive behavioral strategies…

Tweet Me, Message Me, Like Me: Using Social Media to Facilitate Pedagogical Change within an Emerging Community of Practice

ERIC Educational Resources Information Center

Goodyear, Victoria A.; Casey, Ashley; Kirk, David

2014-01-01

While e-support has been positioned as a means, to overcome some of the time and financial constraints to professional learning, it has largely failed to act as a medium for professional learning in physical education. Consequently, this paper positions teachers prior interest with social media acts as a type of "leverage" for using…

Would introverts be better off if they acted more like extraverts? Exploring emotional and cognitive consequences of counterdispositional behavior.

PubMed

Zelenski, John M; Santoro, Maya S; Whelan, Deanna C

2012-04-01

People enjoy acting extraverted, and this seems to apply equally across the dispositional introversion-extraversion dimension (Fleeson, Malanos, & Achille, 2002). It follows that dispositional introverts might improve their happiness by acting more extraverted, yet little research has examined potential costs of this strategy. In two studies, we assessed dispositions, randomly assigned participants to act introverted or extraverted, and examined costs-both emotional (concurrent negative affect) and cognitive (Stroop performance). Results replicated and extended past findings suggesting that acting extraverted produces hedonic benefits regardless of disposition. Positive affect increased and negative affect did not, even for participants acting out of character. In contrast, we found evidence that acting counterdispositionally could produce poor Stroop performance, but this effect was limited to dispositional extraverts who were assigned to act introverted. We suggest that the positive affect produced by introverts' extraverted behavior may buffer the potentially depleting effects of counterdispositional behavior, and we consider alternative explanations. We conclude that dispositional introverts may indeed benefit from acting extraverted more often and caution that dispositional extraverts may want to adopt introverted behavior strategically, as it could induce cognitive costs or self-regulatory depletion more generally. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

77 FR 27263 - Computer Matching Between the Selective Service System and the Department of Education

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-09

... of Education AGENCY: Selective Service System. Action: Notice. In accordance with the Privacy Act of... of Participating Agencies The Selective Service System (SSS) and the Department of Education (ED). 2... [[Page 27264

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

PubMed Central

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

Contemporary evolution during invasion: evidence for differentiation, natural selection, and local adaptation.

PubMed

Colautti, Robert I; Lau, Jennifer A

2015-05-01

Biological invasions are 'natural' experiments that can improve our understanding of contemporary evolution. We evaluate evidence for population differentiation, natural selection and adaptive evolution of invading plants and animals at two nested spatial scales: (i) among introduced populations (ii) between native and introduced genotypes. Evolution during invasion is frequently inferred, but rarely confirmed as adaptive. In common garden studies, quantitative trait differentiation is only marginally lower (~3.5%) among introduced relative to native populations, despite genetic bottlenecks and shorter timescales (i.e. millennia vs. decades). However, differentiation between genotypes from the native vs. introduced range is less clear and confounded by nonrandom geographic sampling; simulations suggest this causes a high false-positive discovery rate (>50%) in geographically structured populations. Selection differentials (¦s¦) are stronger in introduced than in native species, although selection gradients (¦β¦) are not, consistent with introduced species experiencing weaker genetic constraints. This could facilitate rapid adaptation, but evidence is limited. For example, rapid phenotypic evolution often manifests as geographical clines, but simulations demonstrate that nonadaptive trait clines can evolve frequently during colonization (~two-thirds of simulations). Additionally, QST-FST studies may often misrepresent the strength and form of natural selection acting during invasion. Instead, classic approaches in evolutionary ecology (e.g. selection analysis, reciprocal transplant, artificial selection) are necessary to determine the frequency of adaptive evolution during invasion and its influence on establishment, spread and impact of invasive species. These studies are rare but crucial for managing biological invasions in the context of global change. © 2015 John Wiley & Sons Ltd.

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

PubMed Central

Winternitz, Jamie C; Wares, John P

2013-01-01

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

Top-down enhancement and suppression of activity in category-selective extrastriate cortex from an act of reflective attention.

PubMed

Johnson, Matthew R; Johnson, Marcia K

2009-12-01

Recent research has demonstrated top-down attentional modulation of activity in extrastriate category-selective visual areas while stimuli are in view (perceptual attention) and after they are removed from view (reflective attention). Perceptual attention is capable of both enhancing and suppressing activity in category-selective areas relative to a passive viewing baseline. In this study, we demonstrate that a brief, simple act of reflective attention ("refreshing") is also capable of both enhancing and suppressing activity in some scene-selective areas (the parahippocampal place area [PPA]) but not others (refreshing resulted in enhancement but not in suppression in the middle occipital gyrus [MOG]). This suggests that different category-selective extrastriate areas preferring the same class of stimuli may contribute differentially to reflective processing of one's internal representations of such stimuli.

An evaluation of the Adults and Children Together (ACT) Against Violence Parents Raising Safe Kids program.

PubMed

Portwood, Sharon G; Lambert, Richard G; Abrams, Lyndon P; Nelson, Ellissa Brooks

2011-08-01

This study evaluated the effectiveness of the Adults and Children Together (ACT) Against Violence Parents Raising Safe Kids program, developed by the American Psychological Association in collaboration with the National Association for the Education of Young Children, as an economical primary prevention intervention for child maltreatment. Using an experimental design with random assignment to groups, program impact on participating parents' knowledge, behavior, and attitudes compared to those of a comparison group of parents receiving standard community-based support services was examined. As hypothesized, the ACT Parents Raising Safe Kids program achieved positive results in several areas related to effective parenting, including a reduction in the use of harsh verbal and physical discipline and an increase in nurturing behavior. Positive results were observable both at the conclusion of the ACT program and at three-month follow-up. Results further indicated a positive impact on parent expectations and social support for those parents with the greatest need in these areas. Qualitative data collected through focus groups demonstrated that parents themselves perceived numerous benefits to the ACT program, including assistance in controlling their anger, learning and implementing better parenting and discipline strategies, and recognizing when their child's behavior is developmentally appropriate. Overall, findings suggest that the ACT Parents Raising Safe Kids program is a promising primary prevention strategy that can be implemented across diverse community settings.

Positive selection in octopus haemocyanin indicates functional links to temperature adaptation.

PubMed

Oellermann, Michael; Strugnell, Jan M; Lieb, Bernhard; Mark, Felix C

2015-07-05

Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the active centre, suggesting a role as allosteric binding site. The prevalence of methionine at this site in polar octopods, implies regulation of oxygen affinity via increased sensitivity to allosteric metal binding. High sequence conservation of sites directly involved in oxygen binding indicates that functional modifications of octopod haemocyanin rather occur via more subtle mechanisms, as observed in this study.

E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China

PubMed Central

Wen, Qiang; Wang, Tao; Mu, Xuemei; Chenzhang, Yuwei; Cao, Man

2017-01-01

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6. PMID:28141822

40 CFR 105.11 - Who selects the award winners?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Who selects the award winners? 105.11 Section 105.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER THE CLEAN WATER ACT Selection Criteria § 105.11 Who selects the award winners? After...

40 CFR 105.11 - Who selects the award winners?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Who selects the award winners? 105.11 Section 105.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER THE CLEAN WATER ACT Selection Criteria § 105.11 Who selects the award winners? After...

40 CFR 105.11 - Who selects the award winners?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Who selects the award winners? 105.11 Section 105.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER THE CLEAN WATER ACT Selection Criteria § 105.11 Who selects the award winners? After...

40 CFR 105.11 - Who selects the award winners?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Who selects the award winners? 105.11 Section 105.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER THE CLEAN WATER ACT Selection Criteria § 105.11 Who selects the award winners? After...

50 CFR 85.31 - Grant selection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Grant selection. 85.31 Section 85.31...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM CLEAN VESSEL ACT GRANT PROGRAM Grant Selection § 85.31 Grant selection. The Fish and Wildlife Service, Division of Federal Aid, will convene a ranking...

Cross-cultural regularities in the cognitive architecture of pride.

PubMed

Sznycer, Daniel; Al-Shawaf, Laith; Bereby-Meyer, Yoella; Curry, Oliver Scott; De Smet, Delphine; Ermer, Elsa; Kim, Sangin; Kim, Sunhwa; Li, Norman P; Lopez Seal, Maria Florencia; McClung, Jennifer; O, Jiaqing; Ohtsubo, Yohsuke; Quillien, Tadeg; Schaub, Max; Sell, Aaron; van Leeuwen, Florian; Cosmides, Leda; Tooby, John

2017-02-21

Pride occurs in every known culture, appears early in development, is reliably triggered by achievements and formidability, and causes a characteristic display that is recognized everywhere. Here, we evaluate the theory that pride evolved to guide decisions relevant to pursuing actions that enhance valuation and respect for a person in the minds of others. By hypothesis, pride is a neurocomputational program tailored by selection to orchestrate cognition and behavior in the service of: ( i ) motivating the cost-effective pursuit of courses of action that would increase others' valuations and respect of the individual, ( ii ) motivating the advertisement of acts or characteristics whose recognition by others would lead them to enhance their evaluations of the individual, and ( iii ) mobilizing the individual to take advantage of the resulting enhanced social landscape. To modulate how much to invest in actions that might lead to enhanced evaluations by others, the pride system must forecast the magnitude of the evaluations the action would evoke in the audience and calibrate its activation proportionally. We tested this prediction in 16 countries across 4 continents ( n = 2,085), for 25 acts and traits. As predicted, the pride intensity for a given act or trait closely tracks the valuations of audiences, local (mean r = +0.82) and foreign (mean r = +0.75). This relationship is specific to pride and does not generalize to other positive emotions that coactivate with pride but lack its audience-recalibrating function.

Apparent directional selection by biased pleiotropic mutation.

PubMed

Tanaka, Yoshinari

2010-07-01

Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

The close relationship between estimated divergent selection and observed differentiation supports the selective origin of a marine snail hybrid zone.

PubMed

Cruz, R; Vilas, C; Mosquera, J; García, C

2004-11-01

To study the role of divergent selection in the differentiation of the two morphs in a hybrid zone of the intertidal snail Littorina saxatilis, we compared the strength of the divergent selection acting on a series of shell characters (as estimated by the viability of snails in a reciprocal transplant experiment) with the contribution of these characters to the phenotypic differences between the morphs. We found a close correlation between selection and differentiation, which suggests a cause-effect relationship, i.e. that all present differentiation is the result of past divergent selection. In addition, divergent selection was a very important component of the total natural selection acting on shell measures. These novel results support previous evidence, based on allozyme analysis, of a parapatric origin for this hybrid zone. We discuss possible limitations of this interpretation and the circumstances under which allopatric differentiation would produce the same results. Phenotypic analysis of divergent selection may be a useful method of investigating the evolutionary mechanisms involved in differentiation processes.

Reasons Preventing Teachers from Acting within the Framework of Ethical Principles

ERIC Educational Resources Information Center

Dag, Nilgün; Arslantas, Halis Adnan

2015-01-01

This study aims at putting forth the reasons preventing teachers from acting ethically, acting within the framework of ethical principles and having an ethical tendency. This study featuring a qualitative research model taking as a basis the case study approach followed a path of selecting people that can be a rich source of information for…

Programs for Young Children with Disabilities under IDEA: Excerpts from the Twenty-Second Annual Report to Congress on the Implementation of the Individuals with Disabilities Education Act by the U.S. Department of Education (2000).

ERIC Educational Resources Information Center

Trohanis, Pascal

This document reproduces selected information from the U.S. Department of Education's "Twenty-Second Annual Report to Congress on the Implementation of the Individuals with Disabilities Education Act" (2000). These selections consist of text and data tables related to programs for young children with disabilities and their families under…

Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist.

PubMed

Steiner, Michel A; Gatfield, John; Brisbare-Roch, Catherine; Dietrich, Hendrik; Treiber, Alexander; Jenck, Francois; Boss, Christoph

2013-06-01

Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type 1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

["Candidatus contubernalis alkalaceticum," an obligately syntrophic alkaliphilic bacterium capable of anaerobic acetate oxidation in a coculture with Desulfonatronum cooperativum].

PubMed

Zhilina, T N; Zavarzina, D G; Kolganova, T V; Turova, T P; Zavarzin, G A

2005-01-01

From the silty sediments of the Khadyn soda lake (Tuva), a binary sulfidogenic bacterial association capable of syntrophic acetate oxidation at pH 10.0 was isolated. An obligately syntrophic, gram-positive, spore-forming alkaliphilic rod-shaped bacterium performs acetate oxidation in a syntrophic association with a hydrogenotrophic, alkaliphilic sulfate-reducing bacterium; the latter organism was previously isolated and characterized as the new species Desulfonatronum cooperativum. Other sulfate-reducing bacteria of the genera Desulfonatronum and Desulfonatronovibrio can also act as the hydrogenotrophic partner. Apart from acetate, the syntrophic culture can oxidize ethanol, propanol, isopropanol, serine, fructose, and isobutyric acid. Selective amplification of 16S rRNA gene fragments of the acetate-utilizing syntrophic component of the binary culture was performed; it was found to cluster with clones of uncultured gram-positive bacteria within the family Syntrophomonadaceae. The acetate-oxidizing bacterium is thus the first representative of this cluster obtained in a laboratory culture. Based on its phylogenetic position, the new acetate-oxidizing syntrophic bacterium is proposed to be assigned, in a Candidate status, to a new genus and species: "Candidatus Contubernalis alkalaceticum."

5 CFR 319.402 - Scientific and professional positions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS EMPLOYMENT IN SENIOR-LEVEL AND SCIENTIFIC AND PROFESSIONAL POSITIONS Recruitment and Examination § 319.402 Scientific and professional positions. (a) ST positions are filled without competitive... in applicable appropriations acts. (c) ST employees acquire competitive status immediately upon...

Selective constraints, molecular recombination structure and phylogenetic reconstruction of isometric plant RNA viruses of the families Luteoviridae and Tymoviridae.

PubMed

Boulila, Moncef

2011-02-01

In an effort to enhance the knowledge on molecular evolution of currently the known members of the families Luteoviridae and Tymoviridae, in-depth molecular investigations in the entire genome of 147 accessions retrieved from the international databases, were carried out. Two algorithms (RECCO and RDP version 3.31β) adapted to the mosaic structure of viruses were utilized. The recombination frequency along the sequences was dissected and demonstrated that the three virus genera of the family Luteoviridae comprise numerous members subjected to recombination. It has pointed out that the major viruses swapped a few but long genomic segments. In addition, in Barley yellow dwarf virus, heredity material might be exchanged between two different serotypes. Even more, putative recombination events occurred between two different genera. Based on Fisher's Exact Test of Neutrality, positive selection acting on protein expression was detected only in the poleroviruses Cereal yellow dwarf virus, Potato leafroll virus and Wheat yellow dwarf virus. In contrast, several components of the family Tymoviridae were highly recombinant. Genomic portion exchange arose in many positions consisting of short fragments. Furthermore, no positive selection was detected. The evolutionary history showed, in the Luteoviridae, that all screened isolates split into three clusters corresponding to the three virus genera forming this family. Moreover, in the serotype PAV of Barley yellow dwarf virus, two major clades corresponding to PAV-USA and PAV-China, were delineated. Similarly, in the Tymoviridae, all analyzed isolates fell into four groups corresponding to the three virus genera composing this family along with the unclassified Tymoviridae. Inferred phylogenies reshuffled the existing classification and showed that Wheat yellow dwarf virus-RPV was genetically closely related to Cereal yellow dwarf virus and the unclassified Tymoviridae Grapevine syrah virus-1 constituted an integral part of the genus Marafivirus. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Molecular Evolution of Ultraspiracle Protein (USP/RXR) in Insects

PubMed Central

Hult, Ekaterina F.; Tobe, Stephen S.; Chang, Belinda S. W.

2011-01-01

Ultraspiracle protein/retinoid X receptor (USP/RXR) is a nuclear receptor and transcription factor which is an essential component of a heterodimeric receptor complex with the ecdysone receptor (EcR). In insects this complex binds ecdysteroids and plays an important role in the regulation of growth, development, metamorphosis and reproduction. In some holometabolous insects, including Lepidoptera and Diptera, USP/RXR is thought to have experienced several important shifts in function. These include the acquisition of novel ligand-binding properties and an expanded dimerization interface with EcR. In light of these recent hypotheses, we implemented codon-based likelihood methods to investigate if the proposed shifts in function are reflected in changes in site-specific evolutionary rates across functional and structural motifs in insect USP/RXR sequences, and if there is any evidence for positive selection at functionally important sites. Our results reveal evidence of positive selection acting on sites within the loop connecting helices H1 and H3, the ligand-binding pocket, and the dimer interface in the holometabolous lineage leading to the Lepidoptera/Diptera/Trichoptera. Similar analyses conducted using EcR sequences did not indicate positive selection. However, analyses allowing for variation across sites demonstrated elevated non-synonymous/synonymous rate ratios (d N/d S), suggesting relaxed constraint, within the dimerization interface of both USP/RXR and EcR as well as within the coactivator binding groove and helix H12 of USP/RXR. Since the above methods are based on the assumption that d S is constant among sites, we also used more recent models which relax this assumption and obtained results consistent with traditional random-sites models. Overall our findings support the evolution of novel function in USP/RXR of more derived holometabolous insects, and are consistent with shifts in structure and function which may have increased USP/RXR reliance on EcR for cofactor recruitment. Moreover, these findings raise important questions regarding hypotheses which suggest the independent activation of USP/RXR by its own ligand. PMID:21901121

Adjuvant trastuzumab in HER2-positive breast cancer.

PubMed

Slamon, Dennis; Eiermann, Wolfgang; Robert, Nicholas; Pienkowski, Tadeusz; Martin, Miguel; Press, Michael; Mackey, John; Glaspy, John; Chan, Arlene; Pawlicki, Marek; Pinter, Tamas; Valero, Vicente; Liu, Mei-Ching; Sauter, Guido; von Minckwitz, Gunter; Visco, Frances; Bee, Valerie; Buyse, Marc; Bendahmane, Belguendouz; Tabah-Fisch, Isabelle; Lindsay, Mary-Ann; Riva, Alessandro; Crown, John

2011-10-06

Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab. We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety. At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study. The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).

Adjuvant Trastuzumab in HER2-Positive Breast Cancer

PubMed Central

Slamon, Dennis; Eiermann, Wolfgang; Robert, Nicholas; Pienkowski, Tadeusz; Martin, Miguel; Press, Michael; Mackey, John; Glaspy, John; Chan, Arlene; Pawlicki, Marek; Pinter, Tamas; Valero, Vicente; Liu, Mei-Ching; Sauter, Guido; von Minckwitz, Gunter; Visco, Frances; Bee, Valerie; Buyse, Marc; Bendahmane, Belguendouz; Tabah-Fisch, Isabelle; Lindsay, Mary-Ann; Riva, Alessandro; Crown, John

2011-01-01

BACKGROUND Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab. METHODS We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety. RESULTS At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study. CONCLUSIONS The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.) PMID:21991949

Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA.

PubMed

Liro, Małgorzata J; Rose, Lesilee S

2016-11-01

Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. Copyright © 2016 by the Genetics Society of America.

Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA

PubMed Central

Liro, Małgorzata J.; Rose, Lesilee S.

2016-01-01

Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. PMID:27672093

Quantifying Selective Pressures Driving Bacterial Evolution Using Lineage Analysis

NASA Astrophysics Data System (ADS)

Lambert, Guillaume; Kussell, Edo

2015-01-01

Organisms use a variety of strategies to adapt to their environments and maximize long-term growth potential, but quantitative characterization of the benefits conferred by the use of such strategies, as well as their impact on the whole population's rate of growth, remains challenging. Here, we use a path-integral framework that describes how selection acts on lineages—i.e., the life histories of individuals and their ancestors—to demonstrate that lineage-based measurements can be used to quantify the selective pressures acting on a population. We apply this analysis to Escherichia coli bacteria exposed to cyclical treatments of carbenicillin, an antibiotic that interferes with cell-wall synthesis and affects cells in an age-dependent manner. While the extensive characterization of the life history of thousands of cells is necessary to accurately extract the age-dependent selective pressures caused by carbenicillin, the same measurement can be recapitulated using lineage-based statistics of a single surviving cell. Population-wide evolutionary pressures can be extracted from the properties of the surviving lineages within a population, providing an alternative and efficient procedure to quantify the evolutionary forces acting on a population. Importantly, this approach is not limited to age-dependent selection, and the framework can be generalized to detect signatures of other trait-specific selection using lineage-based measurements. Our results establish a powerful way to study the evolutionary dynamics of life under selection and may be broadly useful in elucidating selective pressures driving the emergence of antibiotic resistance and the evolution of survival strategies in biological systems.

Quantifying selective pressures driving bacterial evolution using lineage analysis

PubMed Central

Lambert, Guillaume; Kussell, Edo

2015-01-01

Organisms use a variety of strategies to adapt to their environments and maximize long-term growth potential, but quantitative characterization of the benefits conferred by the use of such strategies, as well as their impact on the whole population’s rate of growth, remains challenging. Here, we use a path-integral framework that describes how selection acts on lineages –i.e. the life-histories of individuals and their ancestors– to demonstrate that lineage-based measurements can be used to quantify the selective pressures acting on a population. We apply this analysis to E. coli bacteria exposed to cyclical treatments of carbenicillin, an antibiotic that interferes with cell-wall synthesis and affects cells in an age-dependent manner. While the extensive characterization of the life-history of thousands of cells is necessary to accurately extract the age-dependent selective pressures caused by carbenicillin, the same measurement can be recapitulated using lineage-based statistics of a single surviving cell. Population-wide evolutionary pressures can be extracted from the properties of the surviving lineages within a population, providing an alternative and efficient procedure to quantify the evolutionary forces acting on a population. Importantly, this approach is not limited to age-dependent selection, and the framework can be generalized to detect signatures of other trait-specific selection using lineage-based measurements. Our results establish a powerful way to study the evolutionary dynamics of life under selection, and may be broadly useful in elucidating selective pressures driving the emergence of antibiotic resistance and the evolution of survival strategies in biological systems. PMID:26213639

Evolution of the complementary sex-determination gene of honey bees: balancing selection and trans-species polymorphisms.

PubMed

Cho, Soochin; Huang, Zachary Y; Green, Daniel R; Smith, Deborah R; Zhang, Jianzhi

2006-11-01

The mechanism of sex determination varies substantively among evolutionary lineages. One important mode of genetic sex determination is haplodiploidy, which is used by approximately 20% of all animal species, including >200,000 species of the entire insect order Hymenoptera. In the honey bee Apis mellifera, a hymenopteran model organism, females are heterozygous at the csd (complementary sex determination) locus, whereas males are hemizygous (from unfertilized eggs). Fertilized homozygotes develop into sterile males that are eaten before maturity. Because homozygotes have zero fitness and because common alleles are more likely than rare ones to form homozygotes, csd should be subject to strong overdominant selection and negative frequency-dependent selection. Under these selective forces, together known as balancing selection, csd is expected to exhibit a high degree of intraspecific polymorphism, with long-lived alleles that may be even older than the species. Here we sequence the csd genes as well as randomly selected neutral genomic regions from individuals of three closely related species, A. mellifera, Apis cerana, and Apis dorsata. The polymorphic level is approximately seven times higher in csd than in the neutral regions. Gene genealogies reveal trans-species polymorphisms at csd but not at any neutral regions. Consistent with the prediction of rare-allele advantage, nonsynonymous mutations are found to be positively selected in csd only in early stages after their appearances. Surprisingly, three different hypervariable repetitive regions in csd are present in the three species, suggesting variable mechanisms underlying allelic specificities. Our results provide a definitive demonstration of balancing selection acting at the honey bee csd gene, offer insights into the molecular determinants of csd allelic specificities, and help avoid homozygosity in bee breeding.

Attributions of responsibility and affective reactions to decision outcomes.

PubMed

Zeelenberg, M; van der Pligt, J; de Vries, N K

2000-06-01

Immediate affective reactions to outcomes are more intense following decisions to act than following decisions not to act. This finding holds for both positive and negative outcomes. We relate this "actor-effect" to attribution theory and argue that decision makers are seen as more responsible for outcomes when these are the result of a decision to act as compared to a decision not to act. Experiment 1 (N = 80) tests the main assumption underlying our reasoning and shows that affective reactions to decision outcomes are indeed more intense when the decision maker is seen as more responsible. Experiment 2 (N = 40) tests whether the actor effect can be predicted on the basis of differential attributions following action and inaction. Participants read vignettes in which active and passive actors obtained a positive or negative outcome. Action resulted in more intense affect than inaction, and positive outcomes resulted in more intense affect than negative outcomes. Experiment 2 further shows that responsibility attributions and affective reactions to outcomes are highly correlated; that is, more extreme affective reactions are associated with more internal attributions. We discuss the implications for research on post-decisional reactions.

Effect of laser pulse on alternative current arc discharge during laser-arc hybrid welding of magnesium alloy

NASA Astrophysics Data System (ADS)

Chen, Minghua; Xin, Lijun; Zhou, Qi; He, Lijia; Wu, Fufa

2018-01-01

The coupling effect between a laser and arc plasma was studied in situations in which the laser acts at the positive and negative waveforms of the arc discharge during the laser-arc hybrid welding of magnesium alloy. Using the methods of direct observation, high speed imaging, and spectral analysis, the surface status of weld seams, weld penetration depths, plasma behavior, and spectral characteristics of welding plasma were investigated, respectively. Results show that, as compared with the laser pulse acting at the negative waveform of the arc plasma discharge, a better weld seam formation can be achieved when the laser pulse acts at the positive waveform of the arc discharge. At the same time, the radiation intensity of Mg atoms in the arc plasma increases significantly. However, the weld penetration depth is weaker. The findings show that when the laser pulse is acting at the negative waveform of the arc plasma discharge, the position of the arc plasma discharge on the workpiece can be restrained by the laser action point, which improves the energy density of the welding arc.

Inferring Fitness Effects from Time-Resolved Sequence Data with a Delay-Deterministic Model

PubMed Central

Nené, Nuno R.; Dunham, Alistair S.; Illingworth, Christopher J. R.

2018-01-01

A common challenge arising from the observation of an evolutionary system over time is to infer the magnitude of selection acting upon a specific genetic variant, or variants, within the population. The inference of selection may be confounded by the effects of genetic drift in a system, leading to the development of inference procedures to account for these effects. However, recent work has suggested that deterministic models of evolution may be effective in capturing the effects of selection even under complex models of demography, suggesting the more general application of deterministic approaches to inference. Responding to this literature, we here note a case in which a deterministic model of evolution may give highly misleading inferences, resulting from the nondeterministic properties of mutation in a finite population. We propose an alternative approach that acts to correct for this error, and which we denote the delay-deterministic model. Applying our model to a simple evolutionary system, we demonstrate its performance in quantifying the extent of selection acting within that system. We further consider the application of our model to sequence data from an evolutionary experiment. We outline scenarios in which our model may produce improved results for the inference of selection, noting that such situations can be easily identified via the use of a regular deterministic model. PMID:29500183

Fitness consequences of larval traits persist across the metamorphic boundary.

PubMed

Crean, Angela J; Monro, Keyne; Marshall, Dustin J

2011-11-01

Metamorphosis is thought to provide an adaptive decoupling between traits specialized for each life-history stage in species with complex life cycles. However, an increasing number of studies are finding that larval traits can carry-over to influence postmetamorphic performance, suggesting that these life-history stages may not be free to evolve independently of each other. We used a phenotypic selection framework to compare the relative and interactive effects of larval size, time to hatching, and time to settlement on postmetamorphic survival and growth in a marine invertebrate, Styela plicata. Time to hatching was the only larval trait found to be under directional selection, individuals that took more time to hatch into larvae survived better after metamorphosis but grew more slowly. Nonlinear selection was found to act on multivariate trait combinations, once again acting in opposite directions for selection acting via survival and growth. Individuals with above average values of larval traits were most likely to survive, but surviving individuals with intermediate larval traits grew to the largest size. These results demonstrate that larval traits can have multiple, complex fitness consequences that persist across the metamorphic boundary; and thus postmetamorphic selection pressures may constrain the evolution of larval traits. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

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

Alcohol and Drug Abuse Education Act Authorization Extension. Hearings Before the Subcommittee on Select Education of the Committee on Education and Labor. House of Representatives, Ninety-Seventh Congress, First Session on H.R. 2644 (March 23 and April 3, 1981).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

These hearings before the Congressional Subcommittee on Select Education consider the extension through fiscal year 1985 of appropriations for programs established by the Alcohol and Drug Abuse Education Act. The text of the extension bill, H.R. 2644, is presented, followed by testimonies from the Department of Education as well as individuals who…

Amendments to the Environmental Education Act of 1970. Hearings before the Select Subcommittee on Education of the Committee on Education and Labor, House of Representatives, Ninety-Third Congress, First Session on H.R.3927.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

Presented in this bulletin is the text of the hearings before the Select Subcommittee on Education of the Committee on Education and Labor concerning a bill to extend the Environmental Education Act of 1970 for three years (HR 3927). The hearings were held April 17, May 15 and 17, 1973, to provide an opportunity for individuals from the public,…

34 CFR 668.37 - Selective Service registration.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Secretary processes a male student's FAFSA, the Secretary determines whether the student is registered with... Selective Service Act. The designated official shall not consider challenges based on constitutional or...

Using ACT Subscores to Identify at Risk Students in Business Statistics and Principles of Management Courses

ERIC Educational Resources Information Center

Welborn, Cliff Alan; Lester, Don; Parnell, John

2015-01-01

The American College Test (ACT) is utilized to determine academic success in business core courses at a midlevel state university. Specifically, subscores are compared to subsequent student grades in selected courses. The results indicate that ACT Mathematics and English subscores are a valid predictor of success or failure of business students in…

12 CFR 268.201 - Age Discrimination in Employment Act.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Age Discrimination in Employment Act. 268.201... Age Discrimination in Employment Act. (a) As an alternative to filing a complaint under this part, an... Commission establishes a maximum age requirement for the position on the basis of a determination that age is...

12 CFR 268.201 - Age Discrimination in Employment Act.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Age Discrimination in Employment Act. 268.201... Complaints § 268.201 Age Discrimination in Employment Act. (a) As an alternative to filing a complaint under... ADEA if the Commission establishes a maximum age requirement for the position on the basis of a...

12 CFR 268.201 - Age Discrimination in Employment Act.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Age Discrimination in Employment Act. 268.201... Age Discrimination in Employment Act. (a) As an alternative to filing a complaint under this part, an... Commission establishes a maximum age requirement for the position on the basis of a determination that age is...

12 CFR 268.201 - Age Discrimination in Employment Act.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Age Discrimination in Employment Act. 268.201... Complaints § 268.201 Age Discrimination in Employment Act. (a) As an alternative to filing a complaint under... ADEA if the Commission establishes a maximum age requirement for the position on the basis of a...

12 CFR 268.201 - Age Discrimination in Employment Act.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Age Discrimination in Employment Act. 268.201... Complaints § 268.201 Age Discrimination in Employment Act. (a) As an alternative to filing a complaint under... ADEA if the Commission establishes a maximum age requirement for the position on the basis of a...

Radiographic Analysis of Simulated First Dorsal Interosseous and Opponens Pollicis Loading Upon Thumb CMC Joint Subluxation: A Cadaver Study.

PubMed

Adams, Julie E; O'Brien, Virginia; Magnusson, Erik; Rosenstein, Benjamin; Nuckley, David J

2018-01-01

Therapy programs to treat thumb carpometacarpal (CMC) arthritis may engage selective activation and reeducation of thenar muscles, particularly the first dorsal interosseous (FDI) and opponens pollicis (OP) to reduce subluxation of the joint. We describe the effect of simulated selective activation of the FDI and OP muscles upon radiographic subluxation of the thumb CMC joint. In a cadaver model of CMC subluxation, loads were applied to the FDI, the OP, and then concomitantly at 0%, 25%, 50%, 75%, and 100% maximal loads and radial subluxation of the joint and reduction in subluxation was measured. Selective activation of the OP, alone, improved the subluxation ratio (SR) in a dose-dependent manner. Selective activation of FDI, alone, demonstrated minimal effects on SR. Concomitant activation of OP and FDI improved the SR across all loading states, and activation of 75% and greater, when compared with FDI activation alone, resulted in a statistically significant improvement in SR to within 10% of the presubluxed joint. Concomitant activation of the FDI and OP acts to reduce subluxation of the thumb CMC joint in a dose-dependent fashion. The OP is likely the predominant reducing force. Hand therapy programs that focus on selective strengthening programs likely function in part to encourage patients to activate the easily palpable and easily understood FDI. Concomitant coactivation of the OP may be the major reducing force to elicit clinical and radiographic reduction of subluxation, improved thumb positioning, and reduction of pain and arthritic symptoms.

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.

Signatures of positive selection and local adaptation to urbanization in white-footed mice (Peromyscus leucopus).

PubMed

Harris, Stephen E; Munshi-South, Jason

2017-11-01

Urbanization significantly alters natural ecosystems and has accelerated globally. Urban wildlife populations are often highly fragmented by human infrastructure, and isolated populations may adapt in response to local urban pressures. However, relatively few studies have identified genomic signatures of adaptation in urban animals. We used a landscape genomic approach to examine signatures of selection in urban populations of white-footed mice (Peromyscus leucopus) in New York City. We analysed 154,770 SNPs identified from transcriptome data from 48 P. leucopus individuals from three urban and three rural populations and used outlier tests to identify evidence of urban adaptation. We accounted for demography by simulating a neutral SNP data set under an inferred demographic history as a null model for outlier analysis. We also tested whether candidate genes were associated with environmental variables related to urbanization. In total, we detected 381 outlier loci and after stringent filtering, identified and annotated 19 candidate loci. Many of the candidate genes were involved in metabolic processes and have well-established roles in metabolizing lipids and carbohydrates. Our results indicate that white-footed mice in New York City are adapting at the biomolecular level to local selective pressures in urban habitats. Annotation of outlier loci suggests selection is acting on metabolic pathways in urban populations, likely related to novel diets in cities that differ from diets in less disturbed areas. © 2017 John Wiley & Sons Ltd.

The Rehabilitation Act of 1973--its impact on employee selection practices.

PubMed

Guy, J H

1978-01-01

The employee selection practices of private and public enterprises that contract with the federal government or receive federal financial assistance have been subjected to extensive regulation by the agencies administering sections 503 and 504 of the 1973 Rehabilitation Act, which provide protection to qualified handicapped individuals. The author discusses the nature and significance of these restrictions and gives practical guidance on compliance. She cautions that the enforcement powers of the agencies administering the Act--the power to cut off federal funds, debar from future contracts, award back pay, and provide equitable relief--make it necessary for employers to show good faith and proper justification when a decision is made to reject a handicapped person for a job or a promotion.

42 CFR 136.331 - Selection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Selection. 136.331 Section 136.331 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF...-Indian Health Scholarship Program § 136.331 Selection. (a) The Secretary, acting through the Service...

Occupational Safety and Health Act: A Responsibility for Science Teachers

ERIC Educational Resources Information Center

Science Teacher, 1974

1974-01-01

Presents implications of the Occupational Safety and Health Act for science teachers both as workers and as they encourage, in students, the development of positive safety attitudes for future occupations. (PEB)

Building and Breaking the Cell Wall in Four Acts: A Kinesthetic and Tactile Role-Playing Exercise for Teaching Beta-Lactam Antibiotic Mechanism of Action and Resistance †

PubMed Central

Popovich, John; Stephens, Michelle; Celaya, Holly; Suwarno, Serena; Barclay, Shizuka; Yee, Emily; Dean, David A.; Farris, Megan; Haydel, Shelley E.

2018-01-01

“Building and breaking the cell wall” is designed to review the bacterial cell envelope, previously learned in lower-division biology classes, while introducing new topics such as antibiotics and bacterial antibiotic resistance mechanisms. We developed a kinesthetic and tactile modeling activity where students act as cellular components and construct the cell wall. In the first two acts, students model a portion of the gram-positive bacterial cell envelope and then demonstrate in detail how the peptidoglycan is formed. Act III involves student demonstration of the addition of β-lactam antibiotics to the environment and how they inhibit the formation of peptidoglycan, thereby preventing bacterial replication. Using Staphylococcus aureus as a model for gram-positive bacteria, students finish the activity (Act IV) by acting out how S. aureus often becomes resistant to β-lactam antibiotics. A high level of student engagement was observed, and the activity received positive feedback. In an assessment administered prior to and two months after the activity, significant improvements in scores were observed (p < 0.0001), demonstrating increased understanding and retention. This activity allows students to (i) visualize, role play, and kinesthetically “build” the cell envelope and form the peptidoglycan layer, (ii) understand the mechanism of action for β-lactam antibiotics, as well as how gene acquisition and protein changes result in resistance, and (iii) work cooperatively and actively to promote long-term retention of the subject material. PMID:29904519

Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing.

PubMed

Bataillon, Thomas; Duan, Jinjie; Hvilsom, Christina; Jin, Xin; Li, Yingrui; Skov, Laurits; Glemin, Sylvain; Munch, Kasper; Jiang, Tao; Qian, Yu; Hobolth, Asger; Wang, Jun; Mailund, Thomas; Siegismund, Hans R; Schierup, Mikkel H

2015-03-30

We study genome-wide nucleotide diversity in three subspecies of extant chimpanzees using exome capture. After strict filtering, Single Nucleotide Polymorphisms and indels were called and genotyped for greater than 50% of exons at a mean coverage of 35× per individual. Central chimpanzees (Pan troglodytes troglodytes) are the most polymorphic (nucleotide diversity, θw = 0.0023 per site) followed by Eastern (P. t. schweinfurthii) chimpanzees (θw = 0.0016) and Western (P. t. verus) chimpanzees (θw = 0.0008). A demographic scenario of divergence without gene flow fits the patterns of autosomal synonymous nucleotide diversity well except for a signal of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked versus autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection statistic exhibits a strong nonmonotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous versus nonsynonymous frequency classes to infer the distribution of S coefficients acting on nonsynonymous mutations in each subspecies. The strength of purifying selection we infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human populations. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Parallel altitudinal clines reveal trends in adaptive evolution of genome size in Zea mays

PubMed Central

Berg, Jeremy J.; Birchler, James A.; Grote, Mark N.; Lorant, Anne; Quezada, Juvenal

2018-01-01

While the vast majority of genome size variation in plants is due to differences in repetitive sequence, we know little about how selection acts on repeat content in natural populations. Here we investigate parallel changes in intraspecific genome size and repeat content of domesticated maize (Zea mays) landraces and their wild relative teosinte across altitudinal gradients in Mesoamerica and South America. We combine genotyping, low coverage whole-genome sequence data, and flow cytometry to test for evidence of selection on genome size and individual repeat abundance. We find that population structure alone cannot explain the observed variation, implying that clinal patterns of genome size are maintained by natural selection. Our modeling additionally provides evidence of selection on individual heterochromatic knob repeats, likely due to their large individual contribution to genome size. To better understand the phenotypes driving selection on genome size, we conducted a growth chamber experiment using a population of highland teosinte exhibiting extensive variation in genome size. We find weak support for a positive correlation between genome size and cell size, but stronger support for a negative correlation between genome size and the rate of cell production. Reanalyzing published data of cell counts in maize shoot apical meristems, we then identify a negative correlation between cell production rate and flowering time. Together, our data suggest a model in which variation in genome size is driven by natural selection on flowering time across altitudinal clines, connecting intraspecific variation in repetitive sequence to important differences in adaptive phenotypes. PMID:29746459

Land Use in the CERCLA Remedy Selection Process

EPA Pesticide Factsheets

This directive presents additional information for considering land use in making remedy selection decisions under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) at National Priorities List (NPL) sites.

7 CFR 58.723 - Basis for selecting cheese for processing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 58.723 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT...

7 CFR 58.723 - Basis for selecting cheese for processing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 58.723 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT...

7 CFR 58.723 - Basis for selecting cheese for processing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 58.723 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

47 CFR 1.2002 - Applicants required to submit information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Grants by Random Selection Implementation of the Anti-Drug Abuse Act of 1988 § 1.2002 Applicants required... benefits that includes FCC benefits pursuant to section 5301 of the Anti-Drug Abuse Act of 1988. 21 U.S.C...

FY2013 National Defense Authorization Act: Selected Military Personnel Policy Issues

DTIC Science & Technology

2013-01-16

Involuntarily Separated Reservists ......................................................................... 29 Autism Treatment...collectively known as the “Selected Reserve”) are eligible to enroll in the TRICARE Reserve Select (TRS) program and TRICARE Dental Program (TDP). TRS is a...family members and military retirees and their dependents. TDP offers dental insurance to active duty family members and Selected Reserve members

Digital high speed programmable convolver

NASA Astrophysics Data System (ADS)

Rearick, T. C.

1984-12-01

A circuit module for rapidly calculating a discrete numerical convolution is described. A convolution such as finding the sum of the products of a 16 bit constant and a 16 bit variable is performed by a module which is programmable so that the constant may be changed for a new problem. In addition, the module may be programmed to find the sum of the products of 4 and 8 bit constants and variables. RAM (Random Access Memories) are loaded with partial products of the selected constant and all possible variables. Then, when the actual variable is loaded, it acts as an address to find the correct partial product in the particular RAM. The partial products from all of the RAMs are shifted to the appropriate numerical power position (if necessary) and then added in adder elements.

Presidential Elections and HIV-Related National Policies and Programs.

PubMed

Holtgrave, David R; Bonacci, Robert A; Valdiserri, Ronald O

2017-03-01

The November 2016 general election and subsequent voting of the Electoral College resulted in the selection of Donald Trump as President of the United States. The incoming Administration ran a campaign that indicated a desire for substantial change in health policy, including the repeal of the Affordable Care Act (ACA). President Trump has said very little directly about HIV programs and policies, but some campaign positions (such as the repeal of the ACA) would clearly and substantially impact the lives of persons living with HIV. In this editorial, we highlight important HIV-related goals to which we must recommit ourselves, and we underscore several key points about evidence-based advocacy that are important to revisit at any time (but most especially when there is a change in Administration).

Special Area Management Plan (SAMP) Upper Yellowstone River, Montana: Environmental Assessment, FONSI, and Selected Alternative

DTIC Science & Technology

2011-04-01

Mitigation Procedure NEPA National Environmental Policy Act NHPA National Historic Preservation Act NRCS Natural Resources Conservation Service NWP...United States Geological Service, Biological Research Division USFWS US Fish and Wildlife Service YNP Yellowstone National Park 4 5 Finding of No...Significant Impact In accordance with the National Environmental Policy Act and its implementing regulations, the attached environmental assessment (EA

Proposed Extension of the Library Services and Construction Act. Hearing before the Subcommittee on Select Education of the Committee on Education and Labor.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The text of oversight hearings on proposals to extend the Library Services and Construction Act (LSCA) includes presentations on the operation of programs authorized under the act. The measure, initially passed in 1964, has provided library services for those without access to them; these included the handicapped, hospitalized, disadvantaged…

The American Recovery and Reinvestment Act of 2009: Selected Funding Streams for Struggling Students and Disconnected Youth

ERIC Educational Resources Information Center

Grant, Elizabeth, Comp.; Johnson, Cassius, Comp.

2009-01-01

On February 17, 2009, President Barack Obama signed the American Recovery and Reinvestment Act, better known as the economic stimulus plan. Congress and the Obama Administration acted in the wake of an economic crisis spurred by a deepening recession. Among its aims in passing the ARRA, Congress moved to help states and local jurisdictions reduce…

School Selection. Updated. Mckinney-Vento Law into Practice Brief Series

ERIC Educational Resources Information Center

National Center for Homeless Education at SERVE, 2014

2014-01-01

Subtitle VII-B of the McKinney-Vento Homeless Assistance Act (42 USC §§11431-11435, 2001; hereafter referred to as "The McKinney-Vento Act"), reauthorized in 2001 by Title X, Part C of the No Child Left Behind Act, guarantees a child or youth identified as homeless the right to attend either the school of origin or the local attendance…

25 CFR 1000.31 - May a Tribe/Consortium be selected to negotiate an AFA under section 403(c) without negotiating...

Code of Federal Regulations, 2010 CFR

2010-04-01

...-DETERMINATION AND EDUCATION ACT Selection of Additional Tribes for Participation in Tribal Self-Governance...). A Tribe may be selected to negotiate an AFA under section 403(c) at the same time that it negotiates...

The Voting Rights Act and Black Electoral Participation.

ERIC Educational Resources Information Center

Thompson, Kenneth H.

An analysis of Census Bureau data on registration and voting by black citizens over the past two decades shows the positive influence of the 1965 Voting Rights Act on electoral participation. After the passage of the act, there was more than a 50% increase in the number of black registered voters. Of black and white citizens participating in the…

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.

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)

17 CFR 1.66 - No-action positions with respect to floor traders.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., in light of the Congressional mandate requiring registration of floor traders under the Act, the... granted or denied registration under the Act, or on June 11, 1993, whichever comes earliest: Provided...

17 CFR 1.66 - No-action positions with respect to floor traders.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., in light of the Congressional mandate requiring registration of floor traders under the Act, the... granted or denied registration under the Act, or on June 11, 1993, whichever comes earliest: Provided...

Detection of aneugenic and clastogenic potential of X-rays, directly and indirectly acting chemicals in human hepatoma (Hep G2) and peripheral blood lymphocytes, using the micronucleus assay and fluorescent in situ hybridization with a DNA centromeric probe.

PubMed

Darroudi, F; Meijers, C M; Hadjidekova, V; Natarajan, A T

1996-09-01

In human hepatoma (Hep G2) cells and peripheral blood lymphocytes (HPBL) the cytokinesis-blocked micronuclei (MN) and fluorescent in situ hybridization (FISH) assays were applied to study aneugenic and clastogenic potentials of X-rays, directly and indirectly acting chemicals. Induction of MN was studied in vitro following treatment with X-rays, directly acting chemicals, such as methylmeth-anesulphonate (MMS), colchicine (COL), vincristine sulphate (VCS) and vinblastine sulphate (VBS), and indirectly acting agents, such as cyclophosphamide (CP), hexamethylphosphoramide (HMPA), 2-acetylaminofluorene (2-AAF) and 4-acetylaminofluorene (4-AAF). Depending on the presence of the fluorescent signal in the MN following FISH with a human DNA centromeric probe, MN in the binucleated Hep G2 cells and lymphocytes were scored as centromere-positive or centromere-negative, representing an aneugenic and clastogenic event respectively. In the controls approximately 50% of spontaneously occurring MN were centromere-positive. Treatment of human hepatoma cells and HPBL (in vitro) with potent aneugens such as COL, VCS and VBS increased the number of MN in a dose-dependent manner; of these 75-93% were centromere-positive. X-irradiation induced MN in a dose-related manner in binucleated Hep G2 cells and HPBL, of which 33-40% were centromere-positive, which demonstrates the significant aneugenic potentials of X-rays. Strong clastogenic activity was observed with MMS and frequency of centromere-positive MN was low: approximately 20 and 30% for HPBL and Hep G2 cells respectively. In Hep G2 cells significant aneugenic activity was found with indirectly acting promutagens/procarcinogens such as HMPA and 2-AAF, in contrast to CP, which came out as a potent clastogen. The non-carcinogen 4-AAF was not able to induce an increase in the frequency of MN in Hep G2 cells. All indirectly acting chemicals tested came out negative when HPBL were used as targets for DNA damage. The results presented correlate positively with data from in vivo assays and indicate that the Hep G2 cell system is a suitable bioactivation system (in vitro) for evaluating the clastogenic and aneugenic potentials of chemicals which require exogenous metabolic activations in order to exert their mutagenic potential.

Evolutionary responses of tree phenology to the combined effects of assortative mating, gene flow and divergent selection

PubMed Central

Soularue, J-P; Kremer, A

2014-01-01

The timing of bud burst (TBB) in temperate trees is a key adaptive trait, the expression of which is triggered by temperature gradients across the landscape. TBB is strongly correlated with flowering time and is therefore probably mediated by assortative mating. We derived theoretical predictions and realized numerical simulations of evolutionary changes in TBB in response to divergent selection and gene flow in a metapopulation. We showed that the combination of the environmental gradient of TBB and assortative mating creates contrasting genetic clines, depending on the direction of divergent selection. If divergent selection acts in the same direction as the environmental gradient (cogradient settings), genetic clines are established and inflated by assortative mating. Conversely, under divergent selection of the same strength but acting in the opposite direction (countergradient selection), genetic clines are slightly constrained. We explored the consequences of these dynamics for population maladaptation, by monitoring pollen swamping. Depending on the direction of divergent selection with respect to the environmental gradient, pollen filtering owing to assortative mating either facilitates or impedes adaptation in peripheral populations. PMID:24924591

Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf

PubMed Central

Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N. W.; Casewell, Nicholas R.; Undheim, Eivind A. B.; Vidal, Nicolas; Ali, Syed A.; King, Glenn F.; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

2013-01-01

Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

Adaptation of the Mitochondrial Genome in Cephalopods: Enhancing Proton Translocation Channels and the Subunit Interactions

PubMed Central

Almeida, Daniela; Maldonado, Emanuel; Vasconcelos, Vitor; Antunes, Agostinho

2015-01-01

Mitochondrial protein-coding genes (mt genes) encode subunits forming complexes of crucial cellular pathways, including those involved in the vital process of oxidative phosphorylation (OXPHOS). Despite the vital role of the mitochondrial genome (mt genome) in the survival of organisms, little is known with respect to its adaptive implications within marine invertebrates. The molluscan Class Cephalopoda is represented by a marine group of species known to occupy contrasting environments ranging from the intertidal to the deep sea, having distinct metabolic requirements, varied body shapes and highly advanced visual and nervous systems that make them highly competitive and successful worldwide predators. Thus, cephalopods are valuable models for testing natural selection acting on their mitochondrial subunits (mt subunits). Here, we used concatenated mt genes from 17 fully sequenced mt genomes of diverse cephalopod species to generate a robust mitochondrial phylogeny for the Class Cephalopoda. We followed an integrative approach considering several branches of interest–covering cephalopods with distinct morphologies, metabolic rates and habitats–to identify sites under positive selection and localize them in the respective protein alignment and/or tridimensional structure of the mt subunits. Our results revealed significant adaptive variation in several mt subunits involved in the energy production pathway of cephalopods: ND5 and ND6 from Complex I, CYTB from Complex III, COX2 and COX3 from Complex IV, and in ATP8 from Complex V. Furthermore, we identified relevant sites involved in protein-interactions, lining proton translocation channels, as well as disease/deficiencies related sites in the aforementioned complexes. A particular case, revealed by this study, is the involvement of some positively selected sites, found in Octopoda lineage in lining proton translocation channels (site 74 from ND5) and in interactions between subunits (site 507 from ND5) of Complex I. PMID:26285039

Insights into the evolution of Darwin’s finches from comparative analysis of the Geospiza magnirostris genome sequence

PubMed Central

2013-01-01

Background A classical example of repeated speciation coupled with ecological diversification is the evolution of 14 closely related species of Darwin’s (Galápagos) finches (Thraupidae, Passeriformes). Their adaptive radiation in the Galápagos archipelago took place in the last 2–3 million years and some of the molecular mechanisms that led to their diversification are now being elucidated. Here we report evolutionary analyses of genome of the large ground finch, Geospiza magnirostris. Results 13,291 protein-coding genes were predicted from a 991.0 Mb G. magnirostris genome assembly. We then defined gene orthology relationships and constructed whole genome alignments between the G. magnirostris and other vertebrate genomes. We estimate that 15% of genomic sequence is functionally constrained between G. magnirostris and zebra finch. Genic evolutionary rate comparisons indicate that similar selective pressures acted along the G. magnirostris and zebra finch lineages suggesting that historical effective population size values have been similar in both lineages. 21 otherwise highly conserved genes were identified that each show evidence for positive selection on amino acid changes in the Darwin's finch lineage. Two of these genes (Igf2r and Pou1f1) have been implicated in beak morphology changes in Darwin’s finches. Five of 47 genes showing evidence of positive selection in early passerine evolution have cilia related functions, and may be examples of adaptively evolving reproductive proteins. Conclusions These results provide insights into past evolutionary processes that have shaped G. magnirostris genes and its genome, and provide the necessary foundation upon which to build population genomics resources that will shed light on more contemporaneous adaptive and non-adaptive processes that have contributed to the evolution of the Darwin’s finches. PMID:23402223

Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

PubMed

Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N W; Casewell, Nicholas R; Undheim, Eivind A B; Vidal, Nicolas; Ali, Syed A; King, Glenn F; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

2013-01-01

Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

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.

77 FR 12646 - Government Securities: Call for Large Position Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF THE TREASURY Government Securities: Call for Large Position Reports AGENCY: Office... exceeded $2 billion as of close of business February 21, 2012. DATES: Large Position Reports must be... is pursuant to the Department's large position reporting rules under the Government Securities Act...

5 CFR 319.402 - Scientific and professional positions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 319.402 Scientific and professional positions. (a) ST positions are filled without competitive examination under 5 U.S.C. 3325. (b) ST positions are not subject to the citizenship requirements in 5 CFR... in applicable appropriations acts. (c) ST employees acquire competitive status immediately upon...

Do males pay for sex? Sex-specific selection coefficients suggest not.

PubMed

Prokop, Zofia M; Prus, Monika A; Gaczorek, Tomasz S; Sychta, Karolina; Palka, Joanna K; Plesnar-Bielak, Agata; Skarboń, Magdalena

2017-03-01

Selection acting on males can reduce mutation load of sexual relative to asexual populations, thus mitigating the twofold cost of sex, provided that it seeks and destroys the same mutations as selection acting on females, but with higher efficiency. This could happen due to sexual selection-a potent evolutionary force that in most systems predominantly affects males. We used replicate populations of red flour beetles (Tribolium castaneum) to study sex-specific selection against deleterious mutations introduced with ionizing radiation. We found no evidence for selection being stronger in males than in females; in fact, we observed a nonsignificant trend in the opposite direction. This suggests that selection on males does not reduce mutation load below the level expected under the (hypothetical) scenario of asexual reproduction. Additionally, we employed a novel approach, based on a simple model, to quantify the relative contributions of sexual and offspring viability selection to the overall selection observed in males. We found them to be similar in magnitude; however, only the offspring viability component was statistically significant. In summary, we found no support for the hypothesis that selection on males in general, and sexual selection in particular, contributes to the evolutionary maintenance of sex. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Genetic variation and selection of MHC class I loci differ in two congeneric frogs.

PubMed

Kiemnec-Tyburczy, Karen M; Tracy, Karen E; Lips, Karen R; Zamudio, Kelly R

2018-04-01

Major histocompatibility complex (MHC) genes encode proteins in the acquired immune response pathway that often show distinctive selection-driven patterns in wild vertebrate populations. We examined genetic variation and signatures of selection in the MHC class I alpha 1 (A1)- and alpha 2 (A2)-domain encoding exons of two frog congeners [Agalychnis callidryas (n = 20) and A. lemur (n = 20)] from a single locality in Panama. We also investigated how historical demographic processes may have impacted MHC genetic diversity by analyzing a neutral mitochondrial marker. We found that both MHC domains were highly variable in both species, with both species likely expressing three loci. Our analyses revealed different signatures of selection between the two species, most notably that the A. callidryas A2 domain had experienced positive selection while the A2 domain of A. lemur had not. Diversifying selection acted on the same number of A1 and A2 allelic lineages, but on a higher percentage of A1 sites compared to A2 sites. Neutrality tests of mitochondrial haplotypes predominately indicated that the two species were at genetic equilibrium when the samples were collected. In addition, two historical tests of demography indicated both species have had relatively stable population sizes over the past 100,000 years; thus large population size changes are unlikely to have greatly influenced MHC diversity in either species during this time period. In conclusion, our results suggest that the impact of selection on MHC diversity varied between these two closely related species, likely due to a combination of distinct ecological conditions and past pathogenic pressures.

Biomechanical calculation of human TM joint loading with jaw opening.

PubMed

Kuboki, T; Takenami, Y; Maekawa, K; Shinoda, M; Yamashita, A; Clark, G T

2000-11-01

A three-dimensional, static mathematical calculation of the stomatognathic system was done to predict total temporomandibular joint (TMJ) loading at different levels of jaw opening. The model assumed that muscle forces acting on the mandible could be simulated by a combination of contractile components (CCs) and elastic components (ECs) and that static equilibrium existed within the body of the mandible. The model also imposed the constraint that any generated joint reaction force would act on the centre of the condyle. The results of the model demonstrated that under all conditions of opening and for all values of the elastic modulus selected, the forces between the TMJ condyle and the articular eminence were compressive in nature. The compressive force magnitude increased from 2.7 to 27.6 N incrementally as the jaw opened from 10 to 40 mm. Overall data in this study indicated that the TMJ tissues undergo low levels of compression at open positions up to 40 mm. Finally, the condition of trismus (increased jaw closing activation with opening) was simulated, the joint reaction force at 20 mm opening increased from 7.7 to 64.9 N with only a 20% activation of the closers.

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

PubMed Central

Frisch, Johanna U.; Häusser, Jan A.; van Dick, Rolf; Mojzisch, Andreas

2015-01-01

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)—a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks. PMID:26649856

The basilar membrane acts as a passive support structure at the cochlear apex

NASA Astrophysics Data System (ADS)

Warren, Rebecca L.; Fridberger, Anders

2015-12-01

The precise mechanical behavior of the basilar membrane (BM) at low frequencies is still unknown. To address this issue we use an in vitro preparation of the guinea pig temporal bone to investigate the mechanical behaviour of the organ of Corti at the apex of the cochlea. Confocal laser interferometry is used to record the nanometre displacements of both Hensen's cells (HeC) and the BM in response to sound and electrical stimulation. We show that at low frequencies, the BM exhibits greatly reduced sound-evoked movement (˜35dB less) and no current-evoked movement, when compared to the HeC at the same position along the spiral. The BM best frequency is found to be an average of 52Hz (0.35 octave) higher than the HeC best frequency. In addition, we demonstrate that BM motion is not affected by inhibition of somatic electromotility or by blocking the mechanoelectrical transduction channels.We therefore propose that the BM primarily acts as a passive support structure at the cochlear apex. We suggest that the micromechanics of the cochlea that are vital to low-frequency amplification and frequency selectivity take place predominantly at the surface of the organ of Corti.

Young Adults' Selection and Use of Dependent Coverage under the Affordable Care Act.

PubMed

Chen, Weiwei

2018-01-01

The dependent coverage expansion under the Affordable Care Act (ACA) required health insurance policies that cover dependents to offer coverage for policyholder' children up to age 26. It has been well documented that the provision successfully reduced the uninsured rate among the young adults. However, less is known about whether dependent coverage crowded out other insurance types and whether young adults used dependent coverage as a fill-in-the-gap short-term option. Using data from the Survey of Income and Program Participation 2008 Panel, the paper assesses dependent coverage uptake and duration before and after the ACA provision among young adults aged 19-26 versus those aged 27-30. Regressions for additional coverage outcomes were also performed to estimate the crowd-out rate. It was found that the ACA provision had a significant positive impact on dependent coverage uptake and duration. The estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most dependent coverage enrollees used the coverage for 1 or 2 years. Differences in dependent coverage uptake and duration remained among racial groups. Less healthy individuals were also less likely to make use of dependent coverage.

Young Adults’ Selection and Use of Dependent Coverage under the Affordable Care Act

PubMed Central

Chen, Weiwei

2018-01-01

The dependent coverage expansion under the Affordable Care Act (ACA) required health insurance policies that cover dependents to offer coverage for policyholder’ children up to age 26. It has been well documented that the provision successfully reduced the uninsured rate among the young adults. However, less is known about whether dependent coverage crowded out other insurance types and whether young adults used dependent coverage as a fill-in-the-gap short-term option. Using data from the Survey of Income and Program Participation 2008 Panel, the paper assesses dependent coverage uptake and duration before and after the ACA provision among young adults aged 19–26 versus those aged 27–30. Regressions for additional coverage outcomes were also performed to estimate the crowd-out rate. It was found that the ACA provision had a significant positive impact on dependent coverage uptake and duration. The estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most dependent coverage enrollees used the coverage for 1 or 2 years. Differences in dependent coverage uptake and duration remained among racial groups. Less healthy individuals were also less likely to make use of dependent coverage. PMID:29445721

Regulators of G-protein signaling and their Gα substrates: promises and challenges in their use as drug discovery targets.

PubMed

Kimple, Adam J; Bosch, Dustin E; Giguère, Patrick M; Siderovski, David P

2011-09-01

Because G-protein coupled receptors (GPCRs) continue to represent excellent targets for the discovery and development of small-molecule therapeutics, it is posited that additional protein components of the signal transduction pathways emanating from activated GPCRs themselves are attractive as drug discovery targets. This review considers the drug discovery potential of two such components: members of the "regulators of G-protein signaling" (RGS protein) superfamily, as well as their substrates, the heterotrimeric G-protein α subunits. Highlighted are recent advances, stemming from mouse knockout studies and the use of "RGS-insensitivity" and fast-hydrolysis mutations to Gα, in our understanding of how RGS proteins selectively act in (patho)physiologic conditions controlled by GPCR signaling and how they act on the nucleotide cycling of heterotrimeric G-proteins in shaping the kinetics and sensitivity of GPCR signaling. Progress is documented regarding recent activities along the path to devising screening assays and chemical probes for the RGS protein target, not only in pursuits of inhibitors of RGS domain-mediated acceleration of Gα GTP hydrolysis but also to embrace the potential of finding allosteric activators of this RGS protein action. The review concludes in considering the Gα subunit itself as a drug target, as brought to focus by recent reports of activating mutations to GNAQ and GNA11 in ocular (uveal) melanoma. We consider the likelihood of several strategies for antagonizing the function of these oncogene alleles and their gene products, including the use of RGS proteins with Gα(q) selectivity.

Repeatable and heritable behavioural variation in a wild cooperative breeder

PubMed Central

Burke, Terry; Dugdale, Hannah L.

2017-01-01

Abstract Quantifying consistent differences in behaviour among individuals is vital to understanding the ecological and evolutionary significance of animal personality. To quantify personality, the phenotypic variation of a behavioural trait is partitioned to assess how it varies among individuals, which is also known as repeatability. If pedigree data are available, the phenotypic variation can then be further partitioned to estimate the additive genetic variance and heritability. Assessing the repeatability and heritability of personality traits therefore allows for a better understanding of what natural selection can act upon, enabling evolution. In a natural population of facultative cooperatively breeding Seychelles warbler (Acrocephalus sechellensis) on Cousin Island, a lack of breeding vacancies forces individuals into different life-history strategies, and these differences in reproductive state could generate behavioural differences among individuals in the population. We used this population to estimate the repeatability of 4 behavioural traits (novel environment exploration, novel object exploration, obstinacy/struggle rate, and escape response), and narrow-sense heritability (of behavior, h2B; behavior minus observer variance; and personality), and evolvability, of the repeatable behavioural traits. We also tested for an among-individual correlation between the repeatable traits. We found that, compared to estimates in other study species, the exploratory behaviours were moderately repeatable (0.23–0.37), there was a positive among-individual correlation (0.51) between novel environment and novel object exploration, and that novel environment exploration was moderately heritable (0.17; h2B was low as it includes observer variance). This study further clarifies the additive genetic variance available for selection to act upon in this cooperatively breeding bird. PMID:29622921

The optimal neural strategy for a stable motor task requires a compromise between level of muscle cocontraction and synaptic gain of afferent feedback

PubMed Central

Dideriksen, Jakob L.; Negro, Francesco

2015-01-01

Increasing joint stiffness by cocontraction of antagonist muscles and compensatory reflexes are neural strategies to minimize the impact of unexpected perturbations on movement. Combining these strategies, however, may compromise steadiness, as elements of the afferent input to motor pools innervating antagonist muscles are inherently negatively correlated. Consequently, a high afferent gain and active contractions of both muscles may imply negatively correlated neural drives to the muscles and thus an unstable limb position. This hypothesis was systematically explored with a novel computational model of the peripheral nervous system and the mechanics of one limb. Two populations of motor neurons received synaptic input from descending drive, spinal interneurons, and afferent feedback. Muscle force, simulated based on motor unit activity, determined limb movement that gave rise to afferent feedback from muscle spindles and Golgi tendon organs. The results indicated that optimal steadiness was achieved with low synaptic gain of the afferent feedback. High afferent gains during cocontraction implied increased levels of common drive in the motor neuron outputs, which were negatively correlated across the two populations, constraining instability of the limb. Increasing the force acting on the joint and the afferent gain both effectively minimized the impact of an external perturbation, and suboptimal adjustment of the afferent gain could be compensated by muscle cocontraction. These observations show that selection of the strategy for a given contraction implies a compromise between steadiness and effectiveness of compensations to perturbations. This indicates that a task-dependent selection of neural strategy for steadiness is necessary when acting in different environments. PMID:26203102

A behavioral perspective on fishing-induced evolution.

PubMed

Uusi-Heikkilä, Silva; Wolter, Christian; Klefoth, Thomas; Arlinghaus, Robert

2008-08-01

The potential for excessive and/or selective fishing to act as an evolutionary force has been emphasized recently. However, most studies have focused on evolution of life-history traits in response to size-selective harvesting. Here we draw attention to fishing-induced evolution of behavioral and underlying physiological traits. We contend that fishing-induced selection directly acting on behavioral rather than on life-history traits per se can be expected in all fisheries that operate with passive gears such as trapping, angling and gill-netting. Recent artificial selection experiments in the nest-guarding largemouth bass Micropterus salmoides suggest that fishing-induced evolution of behavioral traits that reduce exposure to fishing gear might be maladaptive, potentially reducing natural recruitment. To improve understanding and management of fisheries-induced evolution, we encourage greater application of methods from behavioral ecology, physiological ecology and behavioral genetics.

Sexual selection on female ornaments in the sex-role-reversed Gulf pipefish (Syngnathus scovelli).

PubMed

Flanagan, S P; Johnson, J B; Rose, E; Jones, A G

2014-11-01

Understanding how selection acts on traits individually and in combination is an important step in deciphering the mechanisms driving evolutionary change, but for most species, and especially those in which sexual selection acts more strongly on females than on males, we have no estimates of selection coefficients pertaining to the multivariate sexually selected phenotype. Here, we use a laboratory-based mesocosm experiment to quantify pre- and post-mating selection on female secondary sexual traits in the Gulf pipefish (Syngnathus scovelli), a sexually dimorphic, sex-role-reversed species in which ornamented females compete for access to choosy males. We calculate selection differentials and gradients on female traits, including ornament area, ornament number and body size for three episodes of selection related to female reproductive success (number of mates, number of eggs transferred and number of surviving embryos). Selection is strong on both ornament area and ornament size, and the majority of selection occurs during the premating episode of selection. Interestingly, selection on female body size, which has been detected in previous studies of Gulf pipefish, appears to be indirect, as evidenced by a multivariate analysis of selection gradients. Our results show that sexual selection favours either many bands or larger bands in female Gulf pipefish. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Learning about evolution from sequence data

NASA Astrophysics Data System (ADS)

Dayarian, Adel; Shraiman, Boris

2012-02-01

Recent advances in sequencing and in laboratory evolution experiments have made possible to obtain quantitative data on genetic diversity of populations and on the dynamics of evolution. This dynamics is shaped by the interplay between selection acting on beneficial and deleterious mutations and recombination which reshuffles genotypes. Mounting evidence suggests that natural populations harbor extensive fitness diversity, yet most of the currently available tools for analyzing polymorphism data are based on the neutral theory. Our aim is to develop methods to analyze genomic data for populations in the presence of the above-mentioned factors. We consider different evolutionary regimes - Muller's ratchet, mutation-recombination-selection balance and positive adaption rate - and revisit a number of observables considered in the nearly-neutral theory of evolution. In particular, we examine the coalescent structure in the presence of recombination and calculate quantities such as the distribution of the coalescent times along the genome, the distribution of haplotype block sizes and the correlation between ancestors of different loci along the genome. In addition, we characterize the probability and time of fixation of mutations as a function of their fitness effect.

Activity of the pterophyllins 2 and 4 against postharvest fruit pathogenic fungi. Comparison with a synthetic analog and related intermediates.

PubMed

Pergomet, Jorgelina L; Di Liberto, Melina G; Derita, Marcos G; Bracca, Andrea B J; Kaufman, Teodoro S

2018-03-01

The antifungal activity of pterophyllin 2, pterophyllin 4, a 5-desmethyl analog of the latter and some of their synthetic intermediates, against three postharvest phytopathogenic fungi, was evaluated. The target fungi were Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, which affect fruits worldwide, causing important economic losses. The tests were carried out with imazalil and carbendazim as positive controls. Minimum inhibitory concentrations and minimum fungicidal concentrations were determined, and the morphology of the colonies was examined microscopically. In liquid medium, it was found that pterophyllin 4 exhibited selective fungicidal activity toward M. fructicola, whereas its congener pterophyllin 2 proved to be less potent and not selective and the 5-desmethyl analog of pterophyllin 4 displayed a different activity profile. Morphological changes were observed in the colonies exposed to pterophyllin 4. The results highlighted the importance of small structural features for the antifungal behavior and also suggested that, in Nature, the pterophyllins may act as plant defenses against pathogens. Copyright © 2018 Elsevier B.V. All rights reserved.

Differences in evolutionary pressure acting within highly conserved ortholog groups.

PubMed

Przytycka, Teresa M; Jothi, Raja; Aravind, L; Lipman, David J

2008-07-17

In highly conserved widely distributed ortholog groups, the main evolutionary force is assumed to be purifying selection that enforces sequence conservation, with most divergence occurring by accumulation of neutral substitutions. Using a set of ortholog groups from prokaryotes, with a single representative in each studied organism, we asked the question if this evolutionary pressure is acting similarly on different subgroups of orthologs defined as major lineages (e.g. Proteobacteria or Firmicutes). Using correlations in entropy measures as a proxy for evolutionary pressure, we observed two distinct behaviors within our ortholog collection. The first subset of ortholog groups, called here informational, consisted mostly of proteins associated with information processing (i.e. translation, transcription, DNA replication) and the second, the non-informational ortholog groups, mostly comprised of proteins involved in metabolic pathways. The evolutionary pressure acting on non-informational proteins is more uniform relative to their informational counterparts. The non-informational proteins show higher level of correlation between entropy profiles and more uniformity across subgroups. The low correlation of entropy profiles in the informational ortholog groups suggest that the evolutionary pressure acting on the informational ortholog groups is not uniform across different clades considered this study. This might suggest "fine-tuning" of informational proteins in each lineage leading to lineage-specific differences in selection. This, in turn, could make these proteins less exchangeable between lineages. In contrast, the uniformity of the selective pressure acting on the non-informational groups might allow the exchange of the genetic material via lateral gene transfer.

Notification: Review of Inspections and Evaluations of Clean Air Act Sources

EPA Pesticide Factsheets

Project #OPE-FY15-0015, March 12, 2015. The EPA OIG plans to begin preliminary research of the Office of Enforcement and Compliance Assurance (OECA) and selected EPA region's oversight of compliance assurance activities for major Clean Air Act sources.

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...