Identification of positive selection in disease response genes within members of the Poaceae.

PubMed

Rech, Gabriel E; Vargas, Walter A; Sukno, Serenella A; Thon, Michael R

2012-12-01

Millions of years of coevolution between plants and pathogens can leave footprints on their genomes and genes involved on this interaction are expected to show patterns of positive selection in which novel, beneficial alleles are rapidly fixed within the population. Using information about upregulated genes in maize during Colletotrichum graminicola infection and resources available in the Phytozome database, we looked for evidence of positive selection in the Poaceae lineage, acting on protein coding sequences related with plant defense. We found six genes with evidence of positive selection and another eight with sites showing episodic selection. Some of them have already been described as evolving under positive selection, but others are reported here for the first time including genes encoding isocitrate lyase, dehydrogenases, a multidrug transporter, a protein containing a putative leucine-rich repeat and other proteins with unknown functions. Mapping positively selected residues onto the predicted 3-D structure of proteins showed that most of them are located on the surface, where proteins are in contact with other molecules. We present here a set of Poaceae genes that are likely to be involved in plant defense mechanisms and have evidence of positive selection. These genes are excellent candidates for future functional validation.

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

The signature of positive selection at randomly chosen loci.

PubMed

Przeworski, Molly

2002-03-01

In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

Positive selection on the killer whale mitogenome

PubMed Central

Foote, Andrew D.; Morin, Phillip A.; Durban, John W.; Pitman, Robert L.; Wade, Paul; Willerslev, Eske; Gilbert, M. Thomas P.; da Fonseca, Rute R.

2011-01-01

Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches. It is therefore a suitable organism for testing this hypothesis. We compared a global dataset of the complete mitochondrial genomes of 139 individuals for amino acid changes that were associated with radical physico-chemical property changes and were influenced by positive selection. Two such selected non-synonymous amino acid changes were found; one in each of two ecotypes that inhabit the Antarctic pack ice. Both substitutions were associated with changes in local polarity, increased steric constraints and α-helical tendencies that could influence overall metabolic performance, suggesting a functional change. PMID:20810427

Positive selection on the killer whale mitogenome.

PubMed

Foote, Andrew D; Morin, Phillip A; Durban, John W; Pitman, Robert L; Wade, Paul; Willerslev, Eske; Gilbert, M Thomas P; da Fonseca, Rute R

2011-02-23

Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches. It is therefore a suitable organism for testing this hypothesis. We compared a global dataset of the complete mitochondrial genomes of 139 individuals for amino acid changes that were associated with radical physico-chemical property changes and were influenced by positive selection. Two such selected non-synonymous amino acid changes were found; one in each of two ecotypes that inhabit the Antarctic pack ice. Both substitutions were associated with changes in local polarity, increased steric constraints and α-helical tendencies that could influence overall metabolic performance, suggesting a functional change.

Selective arylation and vinylation at the α position of vinylarenes.

PubMed

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

2013-03-04

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

Characterising private and shared signatures of positive selection in 37 Asian populations.

PubMed

Liu, Xuanyao; Lu, Dongsheng; Saw, Woei-Yuh; Shaw, Philip J; Wangkumhang, Pongsakorn; Ngamphiw, Chumpol; Fucharoen, Suthat; Lert-Itthiporn, Worachart; Chin-Inmanu, Kwanrutai; Chau, Tran Nguyen Bich; Anders, Katie; Kasturiratne, Anuradhani; de Silva, H Janaka; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Takeuchi, Fumihiko; Yamamoto, Ken; Yokota, Mitsuhiro; Mamatyusupu, Dolikun; Yang, Wenjun; Chung, Yeun-Jun; Jin, Li; Hoh, Boon-Peng; Wickremasinghe, Ananda R; Ong, RickTwee-Hee; Khor, Chiea-Chuen; Dunstan, Sarah J; Simmons, Cameron; Tongsima, Sissades; Suriyaphol, Prapat; Kato, Norihiro; Xu, Shuhua; Teo, Yik-Ying

2017-04-01

The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection. We performed population structure analyses of the ADP populations and divided these populations into four major groups based on their genographic information. By applying a highly sensitive algorithm haploPS to locate genomic signatures of positive selection, 140 distinct genomic regions exhibiting evidence of positive selection in at least one population were identified. We examined the extent of signal sharing for regions that were selected in multiple populations and observed that populations clustered in a similar fashion to that of how the ancestry clades were phylogenetically defined. In particular, populations predominantly located in South Asia underwent considerably different adaptation as compared with populations from the other geographical regions. Signatures of positive selection present in multiple geographical regions were predicted to be older and have emerged prior to the separation of the populations in the different regions. In contrast, selection signals present in a single population group tended to be of lower frequencies and thus can be attributed to recent evolutionary events.

Characterising private and shared signatures of positive selection in 37 Asian populations

PubMed Central

Liu, Xuanyao; Lu, Dongsheng; Saw, Woei-Yuh; Shaw, Philip J; Wangkumhang, Pongsakorn; Ngamphiw, Chumpol; Fucharoen, Suthat; Lert-itthiporn, Worachart; Chin-inmanu, Kwanrutai; Chau, Tran Nguyen Bich; Anders, Katie; Kasturiratne, Anuradhani; de Silva, H Janaka; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Takeuchi, Fumihiko; Yamamoto, Ken; Yokota, Mitsuhiro; Mamatyusupu, Dolikun; Yang, Wenjun; Chung, Yeun-Jun; Jin, Li; Hoh, Boon-Peng; Wickremasinghe, Ananda R; Ong, RickTwee-Hee; Khor, Chiea-Chuen; Dunstan, Sarah J; Simmons, Cameron; Tongsima, Sissades; Suriyaphol, Prapat; Kato, Norihiro; Xu, Shuhua; Teo, Yik-Ying

2017-01-01

The Asian Diversity Project (ADP) assembled 37 cosmopolitan and ethnic minority populations in Asia that have been densely genotyped across over half a million markers to study patterns of genetic diversity and positive natural selection. We performed population structure analyses of the ADP populations and divided these populations into four major groups based on their genographic information. By applying a highly sensitive algorithm haploPS to locate genomic signatures of positive selection, 140 distinct genomic regions exhibiting evidence of positive selection in at least one population were identified. We examined the extent of signal sharing for regions that were selected in multiple populations and observed that populations clustered in a similar fashion to that of how the ancestry clades were phylogenetically defined. In particular, populations predominantly located in South Asia underwent considerably different adaptation as compared with populations from the other geographical regions. Signatures of positive selection present in multiple geographical regions were predicted to be older and have emerged prior to the separation of the populations in the different regions. In contrast, selection signals present in a single population group tended to be of lower frequencies and thus can be attributed to recent evolutionary events. PMID:28098149

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.

Ongoing Recovery Basic Information Tool (ORBIT)

NASA Technical Reports Server (NTRS)

Oberg, Donald

1993-01-01

The Federal Drug Free Work Place Program (DFWP) has now matured to the point of being able to return employees to sensitive testing designated positions (TDP) after completion of treatment of their addiction. The known tendency of addicted individuals to suffer multiple relapses prior to their final recovery has resulted in several positive urine tests (relapses) occurring among those Federal employees who have already completed treatment and who have been returned to TDP's. The very real potential for further relapses occurring after additional employees return to TDP's will be a critical factor in the ultimate success of the DFWP and in the public's impression of the program's effectiveness. In response to this concern, NASA has begun development of its Ongoing Recovery Basic Information Tool (ORBIT) instrument. The aim of the NASA ORBIT is to provide Employee Assistance Program (EAP) professionals with an advanced clinical tool which will be helpful in supporting recovery from substance abuse and which will allow more accurate determinations of when clients may be successfully returned to sensitive positions.

A Method to Find Longevity-Selected Positions in the Mammalian Proteome

PubMed Central

Semeiks, Jeremy; Grishin, Nick V.

2012-01-01

Evolutionary theory suggests that the force of natural selection decreases with age. To explore the extent to which this prediction directly affects protein structure and function, we used multiple regression to find longevity-selected positions, defined as the columns of a sequence alignment conserved in long-lived but not short-lived mammal species. We analyzed 7,590 orthologous protein families in 33 mammalian species, accounting for body mass, phylogeny, and species-specific mutation rate. Overall, we found that the number of longevity-selected positions in the mammalian proteome is much higher than would be expected by chance. Further, these positions are enriched in domains of several proteins that interact with one another in inflammation and other aging-related processes, as well as in organismal development. We present as an example the kinase domain of anti-Müllerian hormone type-2 receptor (AMHR2). AMHR2 inhibits ovarian follicle recruitment and growth, and a homology model of the kinase domain shows that its longevity-selected positions cluster near a SNP associated with delayed human menopause. Distinct from its canonical role in development, this region of AMHR2 may function to regulate the protein’s activity in a lifespan-specific manner. PMID:22701678

Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

PubMed

Wang, R K; Zhan, S F; Zhao, T J; Zhou, X L; Wang, C E

2015-03-20

Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

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

PubMed

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

2004-03-01

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

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

PubMed

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

2007-10-18

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

The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment.

PubMed

Twigt, J M; Bolhuis, M E C; Steegers, E A P; Hammiche, F; van Inzen, W G; Laven, J S E; Steegers-Theunissen, R P M

2012-08-01

Subfertility and poor nutrition are increasing problems in Western countries. Moreover, nutrition affects fertility in both women and men. In this study, we investigate the association between adherence to general dietary recommendations in couples undergoing IVF/ICSI treatment and the chance of ongoing pregnancy. Between October 2007 and October 2010, couples planning pregnancy visiting the outpatient clinic of the Department of Obstetrics and Gynaecology of the Erasmus Medical Centre in Rotterdam, the Netherlands were offered preconception counselling. Self-administered questionnaires on general characteristics and diet were completed and checked during the visit. Six questions, based on dietary recommendations of the Netherlands Nutrition Centre, covered the intake of six main food groups (fruits, vegetables, meat, fish, whole wheat products and fats). Using the questionnaire results, we calculated the Preconception Dietary Risk score (PDR), providing an estimate of nutritional habits. Dietary quality increases with an increasing PDR score. We define ongoing pregnancy as an intrauterine pregnancy with positive heart action confirmed by ultrasound. For this analysis we selected all couples (n=199) who underwent a first IVF/ICSI treatment within 6 months after preconception counselling. We applied adjusted logistic regression analysis on the outcomes of interest using SPSS. After adjustment for age of the woman, smoking of the woman, PDR of the partner, BMI of the couple and treatment indication we show an association between the PDR of the woman and the chance of ongoing pregnancy after IVF/ICSI treatment (odds ratio 1.65, confidence interval: 1.08-2.52; P=0.02]. Thus, a one-point increase in the PDR score associates with a 65% increased chance of ongoing pregnancy. Our results show that increasing adherence to Dutch dietary recommendations in women undergoing IVF/ICSI treatment increases the chance of ongoing pregnancy. These data warrant further confirmation in

Rapid Detection of Positive Selection in Genes and Genomes Through Variation Clusters

PubMed Central

Wagner, Andreas

2007-01-01

Positive selection in genes and genomes can point to the evolutionary basis for differences among species and among races within a species. The detection of positive selection can also help identify functionally important protein regions and thus guide protein engineering. Many existing tests for positive selection are excessively conservative, vulnerable to artifacts caused by demographic population history, or computationally very intensive. I here propose a simple and rapid test that is complementary to existing tests and that overcomes some of these problems. It relies on the null hypothesis that neutrally evolving DNA regions should show a Poisson distribution of nucleotide substitutions. The test detects significant deviations from this expectation in the form of variation clusters, highly localized groups of amino acid changes in a coding region. In applying this test to several thousand human–chimpanzee gene orthologs, I show that such variation clusters are not generally caused by relaxed selection. They occur in well-defined domains of a protein's tertiary structure and show a large excess of amino acid replacement over silent substitutions. I also identify multiple new human–chimpanzee orthologs subject to positive selection, among them genes that are involved in reproductive functions, immune defense, and the nervous system. PMID:17603100

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

PubMed

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

2009-01-01

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

Human long intrinsically disordered protein regions are frequent targets of positive selection.

PubMed

Afanasyeva, Arina; Bockwoldt, Mathias; Cooney, Christopher R; Heiland, Ines; Gossmann, Toni I

2018-06-01

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species, it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here, we address this question by investigating the evolutionary pattern of more than 6600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a priori knowledge of disordered protein regions, and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs fourfold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts. © 2018 Afanasyeva et al.; Published by Cold Spring Harbor Laboratory Press.

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2006-08-01

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

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

PubMed

Tamir, Maya; Robinson, Michael D

2007-08-01

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

Contribution of Temperature and Precipitation Anomalies to the Ongoing California Drought

NASA Astrophysics Data System (ADS)

Luo, L.; Apps, D.; Arcand, S. E.

2015-12-01

The ongoing multiyear drought over California is a major concern for the residents of the golden state as it brings water restrictions in preparing for water shortages and wild fires due to dry and hot conditions. Both positive temperature and negative precipitation anomalies can contribute to drought developments, but how important are these anomalies for the ongoing California drought? Using the VIC hydrological model, this study investigated the relative contribution of temperature and precipitation anomalies to the ongoing 2011-2015 drought in comparison with another multiyear drought between 1987 and 1992 over the same region. By swapping the observed temperature and precipitation anomalies between two drought events, the study was able to show how temperature and precipitation anomalies and their spatial variability affect other elements of the hydrological cycle including evapotranspiration, soil moisture and streamflow, thus the severity of the drought. The comparison between these two events helps to reveal the unique characteristics of the current drought and provides useful insights for drought prediction and mitigation.

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

PubMed

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

2017-01-21

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

Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans

PubMed Central

Moretti, S.; Davydov, I.I.; Excoffier, L.

2017-01-01

Abstract Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier “significant” genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution. PMID:28333345

Evolution under domestication: ongoing artificial selection and divergence of wild and managed Stenocereus pruinosus (Cactaceae) populations in the Tehuacan Valley, Mexico.

PubMed

Parra, Fabiola; Casas, Alejandro; Peñaloza-Ramírez, Juan Manuel; Cortés-Palomec, Aurea C; Rocha-Ramírez, Víctor; González-Rodríguez, Antonio

2010-09-01

The Tehuacán Valley in Mexico is a principal area of plant domestication in Mesoamerica. There, artificial selection is currently practised on nearly 120 native plant species with coexisting wild, silvicultural and cultivated populations, providing an excellent setting for studying ongoing mechanisms of evolution under domestication. One of these species is the columnar cactus Stenocereus pruinosus, in which we studied how artificial selection is operating through traditional management and whether it has determined morphological and genetic divergence between wild and managed populations. Semi-structured interviews were conducted with 83 households of three villages to investigate motives and mechanisms of artificial selection. Management effects were studied by comparing variation patterns of 14 morphological characters and population genetics (four microsatellite loci) of 264 plants from nine wild, silvicultural and cultivated populations. Variation in fruit characters was recognized by most people, and was the principal target of artificial selection directed to favour larger and sweeter fruits with thinner or thicker peel, fewer spines and pulp colours other than red. Artificial selection operates in agroforestry systems favouring abundance (through not felling plants and planting branches) of the preferred phenotypes, and acts more intensely in household gardens. Significant morphological divergence between wild and managed populations was observed in fruit characters and plant vigour. On average, genetic diversity in silvicultural populations (H(E) = 0.743) was higher than in wild (H(E) = 0.726) and cultivated (H(E) = 0.700) populations. Most of the genetic variation (90.58 %) occurred within populations. High gene flow (Nm(FST) > 2) was identified among almost all populations studied, but was slightly limited by mountains among wild populations, and by artificial selection among wild and managed populations. Traditional management of S. pruinosus involves

Ongoing Inquiry

ERIC Educational Resources Information Center

Ashbrook, Peggy

2011-01-01

An in-depth science inquiry is an ongoing investigation in which children are introduced to materials through hands-on experiences and, with teacher guidance, begin to investigate a question that they can answer through their own actions, observations, and with teacher-assisted research. Qualities that make an experience appropriate to include in…

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.

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

PubMed

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

2014-05-01

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

Results of the Ongoing Monitoring of the Position of a Geostationary Telecommunication Satellite by the Method of Spatially Separated Basis Receiving of Digital Satellite Television Signals

NASA Astrophysics Data System (ADS)

Bushuev, F.; Kaliuzhnyi, M.; Sybiryakova, Y.; Shulga, O.; Moskalenko, S.; Balagura, O.; Kulishenko, V.

2016-10-01

The results of the ongoing monitoring of the position of geostationary telecommunication satellite Eutelsat-13B (13° East) are presented in the article. The results were obtained using a radio engineering complex (RC) of four stations receiving digital satellite television and a data processing centre. The stations are located in Kyiv, Mukachevo, Kharkiv and Mykolaiv. The equipment of each station allows synchronous recording (by the GPS) of fragments of DVB-S signal from the quadrature detector output of the satellite television receiver. Samples of the complex signal are archived and sent to the data processing center through the Internet. Here three linearly independent slant range differences (Δr) for three pairs of the stations are determined as a result of correlation processing of received signals. Every second measured values of Δr are used to calculate Cartesian coordinates (XYZ) of the satellite in the coordinate system WGS84 by multilateration method. The time series of Δr, X, Y and Z obtained during continuous observations from March to May 2015 are presented in the article. Single-measurement errors of Δr, X, Y and Z are equal to 2.6 m, 3540 m, 705 m and 455 m, respectively. The complex is compared with known analogues. Ways of reduction of measurement errors of satellite coordinates are considered. The radio engineering complex could be considered a prototype of a system of independent ongoing monitoring of the position of geostationary telecommunication satellites.

Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection.

PubMed

Chang, Hsiao-Han; Hartl, Daniel L

2015-02-01

Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could influence the patterns of genetic diversity and the power of existing population genetic tools to identify sites under positive selection. We therefore simulated the site-frequency spectrum of a beneficial mutant allele through time under the malaria life cycle. We investigated the power of current population genetic methods to detect positive selection based on the site-frequency spectrum as well as temporal changes in allele frequency. We found that a within-host selective advantage is difficult to detect using these methods. Although a between-host transmission advantage could be detected, the power is decreased when compared with the classical Wright-Fisher (WF) population model. Using an adjusted null site-frequency spectrum that takes the malaria life cycle into account, the power of tests based on the site-frequency spectrum to detect positive selection is greatly improved. Our study demonstrates the importance of considering the life cycle in genetic analysis, especially in parasites with complex life cycles.

Voluntary strategy suppresses the positive impact of preferential selection in prisoner’s dilemma

NASA Astrophysics Data System (ADS)

Sun, Lei; Lin, Pei-jie; Chen, Ya-shan

2014-11-01

Impact of aspiration is ubiquitous in social and biological disciplines. In this work, we try to explore the impact of such a trait on voluntary prisoners’ dilemma game via a selection parameter w. w=0 returns the traditional version of random selection. For positive w, the opponent of high payoff will be selected; while negative w means that the partner of low payoff will be chosen. We find that for positive w, cooperation will be greatly promoted in the interval of small b, at variance cooperation is inhibited with large b. For negative w, cooperation is fully restrained, irrespective of b value. It is found that the positive impact of preferential selection is suppressed by the voluntary strategy in prisoner’s dilemma. These observations can be supported by the spatial patterns. Our work may shed light on the emergence and persistence of cooperation with voluntary participation in social dilemma.

[Adherence to the Ongoing Education Program for family doctors in a southeastern Brazilian state].

PubMed

d'Ávila, Luciana Souza; Assis, Lucília Nunes de; Melo, Marilene Barros de; Brant, Luiz Carlos

2014-02-01

Ongoing Health Education is a strategy for transformation of health practices, though the adherence of professionals is one of the challenges facing its implementation. Thus, the objective of this study was to investigate the factors associated with adherence of family doctors to the Ongoing Education Program in a southeastern Brazilian state from the perception of supervisors. It is a cross-sectional and quantitative study with the use of online questionnaires. Data were analyzed using the chi-square test with ongoing correction to determine the association between structure, topics, activities and difficulties of the supervisors working in Ongoing Health Education, difficulties of the physicians in Primary Health Care (PHC) and poor and good adherence to the program. Excellent medical participation was statistically related to the adequacy of physical space (p = 0.001), a multidisciplinary approach (p = 0.035) and epidemiological aspects (p = 0.043). Low adherence was associated with the inadequacy of the physical structure, difficulty understanding the methodology, less time in a supervisory position, multiple workdays, among others. A good adherence to Ongoing Health Education is a possibility for collective reconstruction of the everyday work of physicians in Primary Health Care.

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Lateralization of noise-burst trains based on onset and ongoing interaural delays.

PubMed

Freyman, Richard L; Balakrishnan, Uma; Zurek, Patrick M

2010-07-01

The lateralization of 250-ms trains of brief noise bursts was measured using an acoustic pointing technique. Stimuli were designed to assess the contribution of the interaural time delay (ITD) of the onset binaural burst relative to that of the ITDs in the ongoing part of the train. Lateralization was measured by listeners' adjustments of the ITD of a pointer stimulus, a 50-ms burst of noise, to match the lateral position of the target train. Results confirmed previous reports of lateralization dominance by the onset burst under conditions in which the train is composed of frozen tokens and the ongoing part contains multiple ambiguous interaural delays. In contrast, lateralization of ongoing trains in which fresh noise tokens were used for each set of two alternating (left-leading/right-leading) binaural pairs followed the ITD of the first pair in each set, regardless of the ITD of the onset burst of the entire stimulus and even when the onset burst was removed by gradual gating. This clear lateralization of a long-duration stimulus with ambiguous interaural delay cues suggests precedence mechanisms that involve not only the interaural cues at the beginning of a sound, but also the pattern of cues within an ongoing sound.

Positive selection drives faster-Z evolution in silkmoths

PubMed Central

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

2014-01-01

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

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

Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals.

PubMed

Huang, Bing-Hong; Liao, Pei-Chun

2015-07-01

Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-α, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Positive and relaxed selection associated with flight evolution and loss in insect transcriptomes

PubMed Central

Mitterboeck, T. Fatima; Liu, Shanlin; Adamowicz, Sarah J.; Fu, Jinzhong; Zhang, Rui; Song, Wenhui; Meusemann, Karen

2017-01-01

Abstract The evolution of powered flight is a major innovation that has facilitated the success of insects. Previously, studies of birds, bats, and insects have detected molecular signatures of differing selection regimes in energy-related genes associated with flight evolution and/or loss. Here, using DNA sequences from more than 1000 nuclear and mitochondrial protein-coding genes obtained from insect transcriptomes, we conduct a broader exploration of which gene categories display positive and relaxed selection at the origin of flight as well as with multiple independent losses of flight. We detected a number of categories of nuclear genes more often under positive selection in the lineage leading to the winged insects (Pterygota), related to catabolic processes such as proteases, as well as splicing-related genes. Flight loss was associated with relaxed selection signatures in splicing genes, mirroring the results for flight evolution. Similar to previous studies of flight loss in various animal taxa, we observed consistently higher nonsynonymous-to-synonymous substitution ratios in mitochondrial genes of flightless lineages, indicative of relaxed selection in energy-related genes. While oxidative phosphorylation genes were not detected as being under selection with the origin of flight specifically, they were most often detected as being under positive selection in holometabolous (complete metamorphosis) insects as compared with other insect lineages. This study supports some convergence in gene-specific selection pressures associated with flight ability, and the exploratory analysis provided some new insights into gene categories potentially associated with the gain and loss of flight in insects. PMID:29020740

Positive and relaxed selection associated with flight evolution and loss in insect transcriptomes.

PubMed

Mitterboeck, T Fatima; Liu, Shanlin; Adamowicz, Sarah J; Fu, Jinzhong; Zhang, Rui; Song, Wenhui; Meusemann, Karen; Zhou, Xin

2017-10-01

The evolution of powered flight is a major innovation that has facilitated the success of insects. Previously, studies of birds, bats, and insects have detected molecular signatures of differing selection regimes in energy-related genes associated with flight evolution and/or loss. Here, using DNA sequences from more than 1000 nuclear and mitochondrial protein-coding genes obtained from insect transcriptomes, we conduct a broader exploration of which gene categories display positive and relaxed selection at the origin of flight as well as with multiple independent losses of flight. We detected a number of categories of nuclear genes more often under positive selection in the lineage leading to the winged insects (Pterygota), related to catabolic processes such as proteases, as well as splicing-related genes. Flight loss was associated with relaxed selection signatures in splicing genes, mirroring the results for flight evolution. Similar to previous studies of flight loss in various animal taxa, we observed consistently higher nonsynonymous-to-synonymous substitution ratios in mitochondrial genes of flightless lineages, indicative of relaxed selection in energy-related genes. While oxidative phosphorylation genes were not detected as being under selection with the origin of flight specifically, they were most often detected as being under positive selection in holometabolous (complete metamorphosis) insects as compared with other insect lineages. This study supports some convergence in gene-specific selection pressures associated with flight ability, and the exploratory analysis provided some new insights into gene categories potentially associated with the gain and loss of flight in insects. © The Authors 2017. Published by Oxford University Press.

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

PubMed

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

2016-06-01

The evolutionary and genomic determinants of sequence evolution in conifers are poorly understood, and previous studies have found only limited evidence for positive selection. Using RNAseq data, we compared gene expression profiles to patterns of divergence and polymorphism in 44 seedlings of lodgepole pine (Pinus contorta) and 39 seedlings of interior spruce (Picea glauca × engelmannii) to elucidate the evolutionary forces that shape their genomes and their plastic responses to abiotic stress. We found that rapidly diverging genes tend to have greater expression divergence, lower expression levels, reduced levels of synonymous site diversity, and longer proteins than slowly diverging genes. Similar patterns were identified for the untranslated regions, but with some exceptions. We found evidence that genes with low expression levels had a larger fraction of nearly neutral sites, suggesting a primary role for negative selection in determining the association between evolutionary rate and expression level. There was limited evidence for differences in the rate of positive selection among genes with divergent versus conserved expression profiles and some evidence supporting relaxed selection in genes diverging in expression between the species. Finally, we identified a small number of genes that showed evidence of site-specific positive selection using divergence data alone. However, estimates of the proportion of sites fixed by positive selection (α) were in the range of other plant species with large effective population sizes suggesting relatively high rates of adaptive divergence among conifers. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fish oil–based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: An ongoing positive experience

USDA-ARS?s Scientific Manuscript database

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, in the use of FOLE in treatment of P...

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

Inhibition of caspases prevents ototoxic and ongoing hair cell death

NASA Technical Reports Server (NTRS)

Matsui, Jonathan I.; Ogilvie, Judith M.; Warchol, Mark E.

2002-01-01

Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

A Demonstration of Regression False Positive Selection in Data Mining

ERIC Educational Resources Information Center

Pinder, Jonathan P.

2014-01-01

Business analytics courses, such as marketing research, data mining, forecasting, and advanced financial modeling, have substantial predictive modeling components. The predictive modeling in these courses requires students to estimate and test many linear regressions. As a result, false positive variable selection ("type I errors") is…

The Ongoing and Open-Ended Simulation

ERIC Educational Resources Information Center

Cohen, Alexander

2016-01-01

This case study explores a novel form of classroom simulation that differs from published examples in two important respects. First, it is ongoing. While most simulations represent a single learning episode embedded within a course, the ongoing simulation is a continuous set of interrelated events and decisions that accompany learning throughout…

Tuning transport selectivity of ionic species by phosphoric acid gradient in positively charged nanochannel membranes.

PubMed

Yang, Meng; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Fan, Xin; Liu, Wei; Liu, Xizhen; Liu, Jianbo; Huang, Jin

2015-02-03

The transport of ionic species through a nanochannel plays important roles in fundamental research and practical applications of the nanofluidic device. Here, we demonstrated that ionic transport selectivity of a positively charged nanochannel membrane can be tuned under a phosphoric acid gradient. When phosphoric acid solution and analyte solution were connected by the positively charged nanochannel membrane, the faster-moving analyte through the positively charged nanochannel membrane was the positively charged dye (methylviologen, MV(2+)) instead of the negatively charged dye (1,5-naphthalene disulfonate, NDS(2-)). In other words, a reversed ion selectivity of the nanochannel membranes can be found. It can be explained as a result of the combination of diffusion, induced electroosmosis, and induced electrophoresis. In addition, the influencing factors of transport selectivity, including concentration of phosphoric acid, penetration time, and volume of feed solution, were also investigated. The results showed that the transport selectivity can further be tuned by adjusting these factors. As a method of tuning ionic transport selectivity by establishing phosphoric acid gradient, it will be conducive to improving the separation of ionic species.

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

PubMed

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

2013-12-27

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

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

PubMed

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

2014-01-01

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

Detecting ongoing intimate partner violence in the emergency department using a simple 4-question screen: the OVAT.

PubMed

Ernst, Amy A; Weiss, Steven J; Cham, Elaine; Hall, Louise; Nick, Todd G

2004-06-01

We wanted to prospectively evaluate the use of a brief screening tool for ongoing intimate partner violence (IPV), the OVAT, and to validate this tool against the present Index of Spouse Abuse (ISA). The design was a prospective survey during randomized 4-hour shifts in an urban emergency department setting. The scale consists of four questions developed based on our previous work. The ISA was compared as the gold standard for detection of present (ongoing) IPV. Of 362 eligible patients presenting during 75 randomized 4-hour shifts, 306 (85%) completed the study. The prevalence of ongoing IPV using the OVAT was 31% (95% CI 26% to 36%). For the ISA, the prevalence was 20% (95% CI 16% to 25%). Compared with the ISA, the sensitivity of the OVAT in detecting ongoing IPV was 86%, specificity 83%, negative predictive value 96%, positive predictive value 56%, with an accuracy of 84%. In conclusion, four brief questions can detect ongoing IPV to aid in identifying the victim.

Selective Imaging of Gram-Negative and Gram-Positive Microbiotas in the Mouse Gut.

PubMed

Wang, Wei; Zhu, Yuntao; Chen, Xing

2017-08-01

The diverse gut microbial communities are crucial for host health. How the interactions between microbial communities and between host and microbes influence the host, however, is not well understood. To facilitate gut microbiota research, selective imaging of specific groups of microbiotas in the gut is of great utility but remains technically challenging. Here we present a chemical approach that enables selective imaging of Gram-negative and Gram-positive microbiotas in the mouse gut by exploiting their distinctive cell wall components. Cell-selective labeling is achieved by the combined use of metabolic labeling of Gram-negative bacterial lipopolysaccharides with a clickable azidosugar and direct labeling of Gram-positive bacteria with a vancomycin-derivatized fluorescent probe. We demonstrated this strategy by two-color fluorescence imaging of Gram-negative and Gram-positive gut microbiotas in the mouse intestines. This chemical method should be broadly applicable to different gut microbiota research fields and other bacterial communities studied in microbiology.

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

PubMed

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

2015-08-01

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

Dominant positive and negative selection using a hygromycin phosphotransferase-thymidine kinase fusion gene.

PubMed

Lupton, S D; Brunton, L L; Kalberg, V A; Overell, R W

1991-06-01

The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable phenotypes may be expressed and regulated as a single genetic entity.

DoD Permanently Discontinues Procurement of Global Positioning System Selective Availability

DOT National Transportation Integrated Search

2007-09-18

The Department of Defense announced today that it intends to stop procuring Global Positioning System : (GPS) satellites with the capability to intentionally degrade the accuracy of civil signals. : This capability, known as Selective Availability (S...

Mathematical Optimization Algorithm for Minimizing the Cost Function of GHG Emission in AS/RS Using Positive Selection Based Clonal Selection Principle

NASA Astrophysics Data System (ADS)

Mahalakshmi; Murugesan, R.

2018-04-01

This paper regards with the minimization of total cost of Greenhouse Gas (GHG) efficiency in Automated Storage and Retrieval System (AS/RS). A mathematical model is constructed based on tax cost, penalty cost and discount cost of GHG emission of AS/RS. A two stage algorithm namely positive selection based clonal selection principle (PSBCSP) is used to find the optimal solution of the constructed model. In the first stage positive selection principle is used to reduce the search space of the optimal solution by fixing a threshold value. In the later stage clonal selection principle is used to generate best solutions. The obtained results are compared with other existing algorithms in the literature, which shows that the proposed algorithm yields a better result compared to others.

Evidence for Positive Selection on the Leptin Gene in Cetacea and Pinnipedia

PubMed Central

Zhang, Xin; Wang, Ding; Zheng, Jin-song; Yang, Guang; Xu, Shi-xia; Cho, Soochin; Zhang, Ya-ping

2011-01-01

The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales) of the Cetacea and the family Phocidae (earless seals) of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR) sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive evolution of the

Selection of Patients in Ongoing Clinical Trials on Lung Cancer.

PubMed

Schulkes, Karlijn J G; Nguyen, Cindy; van den Bos, Frederiek; van Elden, Leontine J R; Hamaker, Marije E

2016-12-01

Lung cancer is predominantly a disease of the elderly: half of all newly diagnosed patients are over 70 years old. Older patients and those with comorbidities are underrepresented in clinical trials; scientific communities have addressed this issue since the end of the 20th century. We set out to determine the characteristics of the selection of patients in lung cancer trials that are currently recruiting. We searched The United States National Institutes of Health (NIH) clinical trial registry ( www.clinicaltrials.gov ) on April 23, 2015 for currently recruiting phase I, II, or III clinical trials in lung cancer. Trial characteristics and study objectives were extracted from the registry website. Of the 419 trails selected in this overview, 88 % explicitly or implicitly excluded elderly patients. Patients were excluded based on stringent organ selection in 76 % of the trials, based on performance status (57 %) and based on age (13 %). The median number of placed restrictions per trial was seven. In the 2 % of the trials that were exclusively designed for elderly patients only fit patients were included. In this overview of current lung cancer trials registered in the NIH clinical trial registry, we found that elderly patients and those with comorbidities are often excluded from participation in clinical trials. Therefore, it is difficult for physicians and their frail patients to properly evaluate the efficacy and safety of current treatment options. More research that includes the elderly and those with comorbidities is urgently needed.

Thinking too positive? Revisiting current methods of population genetic selection inference.

PubMed

Bank, Claudia; Ewing, Gregory B; Ferrer-Admettla, Anna; Foll, Matthieu; Jensen, Jeffrey D

2014-12-01

In the age of next-generation sequencing, the availability of increasing amounts and improved quality of data at decreasing cost ought to allow for a better understanding of how natural selection is shaping the genome than ever before. However, alternative forces, such as demography and background selection (BGS), obscure the footprints of positive selection that we would like to identify. In this review, we illustrate recent developments in this area, and outline a roadmap for improved selection inference. We argue (i) that the development and obligatory use of advanced simulation tools is necessary for improved identification of selected loci, (ii) that genomic information from multiple time points will enhance the power of inference, and (iii) that results from experimental evolution should be utilized to better inform population genomic studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evolution of the core and pan-genome of Streptococcus: positive selection, recombination, and genome composition

PubMed Central

Lefébure, Tristan; Stanhope, Michael J

2007-01-01

Background The genus Streptococcus is one of the most diverse and important human and agricultural pathogens. This study employs comparative evolutionary analyses of 26 Streptococcus genomes to yield an improved understanding of the relative roles of recombination and positive selection in pathogen adaptation to their hosts. Results Streptococcus genomes exhibit extreme levels of evolutionary plasticity, with high levels of gene gain and loss during species and strain evolution. S. agalactiae has a large pan-genome, with little recombination in its core-genome, while S. pyogenes has a smaller pan-genome and much more recombination of its core-genome, perhaps reflecting the greater habitat, and gene pool, diversity for S. agalactiae compared to S. pyogenes. Core-genome recombination was evident in all lineages (18% to 37% of the core-genome judged to be recombinant), while positive selection was mainly observed during species differentiation (from 11% to 34% of the core-genome). Positive selection pressure was unevenly distributed across lineages and biochemical main role categories. S. suis was the lineage with the greatest level of positive selection pressure, the largest number of unique loci selected, and the largest amount of gene gain and loss. Conclusion Recombination is an important evolutionary force in shaping Streptococcus genomes, not only in the acquisition of significant portions of the genome as lineage specific loci, but also in facilitating rapid evolution of the core-genome. Positive selection, although undoubtedly a slower process, has nonetheless played an important role in adaptation of the core-genome of different Streptococcus species to different hosts. PMID:17475002

Determination of Azimuth Angle at Burnout for Placing a Satellite Over a Selected Earth Position

NASA Technical Reports Server (NTRS)

Skopinski, T. H.; Johnson, Katherine G.

1960-01-01

Expressions are presented for relating the satellite position in the orbital plane with the projected latitude and longitude on a rotating earth surface. An expression is also presented for determining the azimuth angle at a given burnout position on the basis of a selected passage position on the earth's surface. Examples are presented of a satellite launched eastward and one launched westward, each passing over a selected position sometime after having completed three orbits. Incremental changes from the desired latitude and longitude due to the earth's oblateness are included in the iteration for obtaining the azimuth angles of the two examples. The results for both cases are then compared with those obtained from a computing program using an oblate rotating earth. Changes from the selected latitude and longitude resulting from incremental changes from the burn-out azimuth angle and latitude are also analyzed.

Evolution of Genes Involved in Gamete Interaction: Evidence for Positive Selection, Duplications and Losses in Vertebrates

PubMed Central

Callebaut, Isabelle; Laurin, Michel; Pascal, Géraldine; Poupon, Anne; Goudet, Ghylène; Monget, Philippe

2012-01-01

Genes encoding proteins involved in sperm-egg interaction and fertilization exhibit a particularly fast evolution and may participate in prezygotic species isolation [1], [2]. Some of them (ZP3, ADAM1, ADAM2, ACR and CD9) have individually been shown to evolve under positive selection [3], [4], suggesting a role of positive Darwinian selection on sperm-egg interaction. However, the genes involved in this biological function have not been systematically and exhaustively studied with an evolutionary perspective, in particular across vertebrates with internal and external fertilization. Here we show that 33 genes among the 69 that have been experimentally shown to be involved in fertilization in at least one taxon in vertebrates are under positive selection. Moreover, we identified 17 pseudogenes and 39 genes that have at least one duplicate in one species. For 15 genes, we found neither positive selection, nor gene copies or pseudogenes. Genes of teleosts, especially genes involved in sperm-oolemma fusion, appear to be more frequently under positive selection than genes of birds and eutherians. In contrast, pseudogenization, gene loss and gene gain are more frequent in eutherians. Thus, each of the 19 studied vertebrate species exhibits a unique signature characterized by gene gain and loss, as well as position of amino acids under positive selection. Reflecting these clade-specific signatures, teleosts and eutherian mammals are recovered as clades in a parsimony analysis. Interestingly the same analysis places Xenopus apart from teleosts, with which it shares the primitive external fertilization, and locates it along with amniotes (which share internal fertilization), suggesting that external or internal environmental conditions of germ cell interaction may not be the unique factors that drive the evolution of fertilization genes. Our work should improve our understanding of the fertilization process and on the establishment of reproductive barriers, for example by

Positive allometry and the prehistory of sexual selection.

PubMed

Tomkins, Joseph L; LeBas, Natasha R; Witton, Mark P; Martill, David M; Humphries, Stuart

2010-08-01

The function of the exaggerated structures that adorn many fossil vertebrates remains largely unresolved. One recurrent hypothesis is that these elaborated traits had a role in thermoregulation. This orthodoxy persists despite the observation that traits exaggerated to the point of impracticality in extant organisms are almost invariably sexually selected. We use allometric scaling to investigate the role of sexual selection and thermoregulation in the evolution of exaggerated traits of the crested pterosaur Pteranodon longiceps and the sail-backed eupelycosaurs Dimetrodon and Edaphosaurus. The extraordinarily steep positive allometry of the head crest of Pteranodon rules out all of the current hypotheses for this trait's main function other than sexual signaling. We also find interspecific patterns of allometry and sexual dimorphism in the sails of Dimetrodon and patterns of elaboration in Edaphosaurus consistent with a sexually selected function. Furthermore, small ancestral, sail-backed pelycosaurs would have been too small to need adaptations to thermoregulation. Our results question the popular view that the elaborated structures of these fossil species evolved as thermoregulatory organs and provide evidence in support of the hypothesis that Pteranodon crests and eupelycosaur sails are among the earliest and most extreme examples of elaborate sexual signals in the evolution of terrestrial vertebrates.

FOXP2 Targets Show Evidence of Positive Selection in European Populations

PubMed Central

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

2013-01-01

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

Can monaural temporal masking explain the ongoing precedence effect?

PubMed

Freyman, Richard L; Morse-Fortier, Charlotte; Griffin, Amanda M; Zurek, Patrick M

2018-02-01

The precedence effect for transient sounds has been proposed to be based primarily on monaural processes, manifested by asymmetric temporal masking. This study explored the potential for monaural explanations with longer ("ongoing") sounds exhibiting the precedence effect. Transient stimuli were single lead-lag noise burst pairs; ongoing stimuli were trains of 63 burst pairs. Unlike with transients, monaural masking data for ongoing sounds showed no advantage for the lead, and are inconsistent with asymmetric audibility as an explanation for ongoing precedence. This result, along with supplementary measurements of interaural time discrimination, suggests different explanations for transient and ongoing precedence.

A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning.

PubMed

Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

2015-10-30

The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different

A Mixed Approach to Similarity Metric Selection in Affinity Propagation-Based WiFi Fingerprinting Indoor Positioning

PubMed Central

Caso, Giuseppe; de Nardis, Luca; di Benedetto, Maria-Gabriella

2015-01-01

The weighted k-nearest neighbors (WkNN) algorithm is by far the most popular choice in the design of fingerprinting indoor positioning systems based on WiFi received signal strength (RSS). WkNN estimates the position of a target device by selecting k reference points (RPs) based on the similarity of their fingerprints with the measured RSS values. The position of the target device is then obtained as a weighted sum of the positions of the k RPs. Two-step WkNN positioning algorithms were recently proposed, in which RPs are divided into clusters using the affinity propagation clustering algorithm, and one representative for each cluster is selected. Only cluster representatives are then considered during the position estimation, leading to a significant computational complexity reduction compared to traditional, flat WkNN. Flat and two-step WkNN share the issue of properly selecting the similarity metric so as to guarantee good positioning accuracy: in two-step WkNN, in particular, the metric impacts three different steps in the position estimation, that is cluster formation, cluster selection and RP selection and weighting. So far, however, the only similarity metric considered in the literature was the one proposed in the original formulation of the affinity propagation algorithm. This paper fills this gap by comparing different metrics and, based on this comparison, proposes a novel mixed approach in which different metrics are adopted in the different steps of the position estimation procedure. The analysis is supported by an extensive experimental campaign carried out in a multi-floor 3D indoor positioning testbed. The impact of similarity metrics and their combinations on the structure and size of the resulting clusters, 3D positioning accuracy and computational complexity are investigated. Results show that the adoption of metrics different from the one proposed in the original affinity propagation algorithm and, in particular, the combination of different

Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

PubMed

Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

2014-05-01

The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

Positive selection moments identify potential functional residues in human olfactory receptors

NASA Technical Reports Server (NTRS)

Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

1996-01-01

Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

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

PubMed

Jiggins, F M; Kim, K W

2007-05-01

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

Evolution under domestication: ongoing artificial selection and divergence of wild and managed Stenocereus pruinosus (Cactaceae) populations in the Tehuacán Valley, Mexico

PubMed Central

Parra, Fabiola; Casas, Alejandro; Peñaloza-Ramírez, Juan Manuel; Cortés-Palomec, Aurea C.; Rocha-Ramírez, Víctor; González-Rodríguez, Antonio

2010-01-01

Background and Aims The Tehuacán Valley in Mexico is a principal area of plant domestication in Mesoamerica. There, artificial selection is currently practised on nearly 120 native plant species with coexisting wild, silvicultural and cultivated populations, providing an excellent setting for studying ongoing mechanisms of evolution under domestication. One of these species is the columnar cactus Stenocereus pruinosus, in which we studied how artificial selection is operating through traditional management and whether it has determined morphological and genetic divergence between wild and managed populations. Methods Semi-structured interviews were conducted with 83 households of three villages to investigate motives and mechanisms of artificial selection. Management effects were studied by comparing variation patterns of 14 morphological characters and population genetics (four microsatellite loci) of 264 plants from nine wild, silvicultural and cultivated populations. Key Results Variation in fruit characters was recognized by most people, and was the principal target of artificial selection directed to favour larger and sweeter fruits with thinner or thicker peel, fewer spines and pulp colours others than red. Artificial selection operates in agroforestry systems favouring abundance (through not felling plants and planting branches) of the preferred phenotypes, and acts more intensely in household gardens. Significant morphological divergence between wild and managed populations was observed in fruit characters and plant vigour. On average, genetic diversity in silvicultural populations (HE = 0·743) was higher than in wild (HE = 0·726) and cultivated (HE = 0·700) populations. Most of the genetic variation (90·58 %) occurred within populations. High gene flow (NmFST > 2) was identified among almost all populations studied, but was slightly limited by mountains among wild populations, and by artificial selection among wild and managed populations. Conclusions

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

PubMed

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

2001-11-01

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

FOXP2 targets show evidence of positive selection in European populations.

PubMed

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

2013-05-02

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

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

PubMed

Taye, Mengistie; Lee, Wonseok; Caetano-Anolles, Kelsey; Dessie, Tadelle; Hanotte, Olivier; Mwai, Okeyo Ally; Kemp, Stephen; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

2017-12-01

As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study. © 2017 Japanese Society of Animal Science.

Selective inhibition of a multicomponent response can be achieved without cost

PubMed Central

Westrick, Zachary; Ivry, Richard B.

2014-01-01

Behavioral flexibility frequently requires the ability to modify an on-going action. In some situations, optimal performance requires modifying some components of an on-going action without interrupting other components of that action. This form of control has been studied with the selective stop-signal task, in which participants are instructed to abort only one movement of a multicomponent response. Previous studies have shown a transient disruption of the nonaborted component, suggesting limitations in our ability to use selective inhibition. This cost has been attributed to a structural limitation associated with the recruitment of a cortico-basal ganglia pathway that allows for the rapid inhibition of action but operates in a relatively generic manner. Using a model-based approach, we demonstrate that, with a modest amount of training and highly compatible stimulus-response mappings, people can perform a selective-stop task without any cost on the nonaborted component. Prior reports of behavioral costs in selective-stop tasks reflect, at least in part, a sampling bias in the method commonly used to estimate such costs. These results suggest that inhibition can be selectively controlled and present a challenge for models of inhibitory control that posit the operation of generic processes. PMID:25339712

Posttraumatic stress disorder among preschoolers exposed to ongoing missile attacks in the Gaza war.

PubMed

Kaufman-Shriqui, Vered; Werbeloff, Nomi; Faroy, Michal; Meiri, Gal; Shahar, Danit R; Fraser, Drora; Novack, Yelena; Bilenko, Natalya; Vardi, Hillel; Elhadad, Naama; Pietrzak, Robert H; Harpaz-Rotem, Ilan

2013-05-01

The prevalence and manifestation of posttraumatic stress symptoms in young children may differ from that observed in adults. This study examined sociodemographic, familial, and psychosomatic correlates of posttraumatic stress disorder (PTSD) among preschool children and their mothers who had been exposed to ongoing missile attacks in the Gaza war. One hundred and sixty-seven mothers of preschoolers (aged 4.0-6.5 years) were interviewed regarding PTSD and psychosomatic symptomatology of their children, as well as their own reactions to trauma. Fourteen mothers (8.4%) and 35 children (21.0%) screened positive for PTSD. Sociodemographic characteristics were not associated with PTSD among mothers or children. Among children, the only significant risk factor was having a mother with PTSD (OR = 12.22, 95% CI 2.75-54.28). Compared to children who did not screen positive for PTSD, those who did screen positive displayed significantly higher rates of psychosomatic reactions to trauma, most notably constipation or diarrhea (OR = 4.36, 95% CI 1.64-11.60) and headaches (OR = 2.91, 95% CI 1.07-7.94). Results of this study add to the burgeoning literature on child PTSD, emphasizing the important role of maternal anxiety and the psychosomatic reactions associated with exposure to ongoing traumatic experiences in young children. © 2013 Wiley Periodicals, Inc.

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.

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

PubMed

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

2018-04-01

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

Mode Selection Rules for a Two-Delay System with Positive and Negative Feedback Loops

NASA Astrophysics Data System (ADS)

Takahashi, Kin'ya; Kobayashi, Taizo

2018-04-01

The mode selection rules for a two-delay system, which has negative feedback with a short delay time t1 and positive feedback with a long delay time t2, are studied numerically and theoretically. We find two types of mode selection rules depending on the strength of the negative feedback. When the strength of the negative feedback |α1| (α1 < 0) is sufficiently small compared with that of the positive feedback α2 (> 0), 2m + 1-th harmonic oscillation is well sustained in a neighborhood of t1/t2 = even/odd, i.e., relevant condition. In a neighborhood of the irrelevant condition given by t1/t2 = odd/even or t1/t2 = odd/odd, higher harmonic oscillations are observed. However, if |α1| is slightly less than α2, a different mode selection rule works, where the condition t1/t2 = odd/even is relevant and the conditions t1/t2 = odd/odd and t1/t2 = even/odd are irrelevant. These mode selection rules are different from the mode selection rule of the normal two-delay system with two positive feedback loops, where t1/t2 = odd/odd is relevant and the others are irrelevant. The two types of mode selection rules are induced by individually different mechanisms controlling the Hopf bifurcation, i.e., the Hopf bifurcation controlled by the "boosted bifurcation process" and by the "anomalous bifurcation process", which occur for |α1| below and above the threshold value αth, respectively.

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

PubMed

Dasmeh, Pouria; Kepp, Kasper P

2017-08-01

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

Detecting signatures of positive selection associated with musical aptitude in the human genome

PubMed Central

Liu, Xuanyao; Kanduri, Chakravarthi; Oikkonen, Jaana; Karma, Kai; Raijas, Pirre; Ukkola-Vuoti, Liisa; Teo, Yik-Ying; Järvelä, Irma

2016-01-01

Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and FST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude. PMID:26879527

Detecting signatures of positive selection associated with musical aptitude in the human genome.

PubMed

Liu, Xuanyao; Kanduri, Chakravarthi; Oikkonen, Jaana; Karma, Kai; Raijas, Pirre; Ukkola-Vuoti, Liisa; Teo, Yik-Ying; Järvelä, Irma

2016-02-16

Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and FST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude.

Trauma-Focused CBT for Youth who Experience Ongoing Traumas

PubMed Central

Cohen, Judith A.; Mannarino, Anthony P.; Murray, Laura A.

2011-01-01

Many youth experience ongoing trauma exposure, such as domestic or community violence. Clinicians often ask whether evidence-based treatments containing exposure components to reduce learned fear responses to historical trauma are appropriate for these youth. Essentially the question is, if youth are desensitized to their trauma experiences, will this in some way impair their responding to current or ongoing trauma? The paper addresses practical strategies for implementing one evidence-based treatment, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth with ongoing traumas. Collaboration with local therapists and families participating in TF-CBT community and international programs elucidated effective strategies for applying TF-CBT with these youth. These strategies included: 1) enhancing safety early in treatment; 2) effectively engaging parents who experience personal ongoing trauma; and 3) during the trauma narrative and processing component focusing on a) increasing parental awareness and acceptance of the extent of the youths’ ongoing trauma experiences; b) addressing youths’ maladaptive cognitions about ongoing traumas; and c) helping youth differentiate between real danger and generalized trauma reminders. Case examples illustrate how to use these strategies in diverse clinical situations. Through these strategies TF-CBT clinicians can effectively improve outcomes for youth experiencing ongoing traumas. PMID:21855140

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

PubMed Central

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M.; Small, Kerrin S.; Clark, Taane G.; Kwiatkowski, Dominic P.; Teo, Yik-Ying

2013-01-01

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. PMID:23731540

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

PubMed

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

2006-05-01

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

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

PubMed

Beck, Emily A; Llopart, Ana

2015-11-25

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

Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis.

PubMed

Inada, Keiji; Okumura, Meinoshin; Shiono, Hiroyuki; Inoue, Masayoshi; Kadota, Yoshihisa; Ohta, Mitsunori; Matsuda, Hikaru

2005-06-01

A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

Detecting and characterizing genomic signatures of positive selection in global populations.

PubMed

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M; Small, Kerrin S; Clark, Taane G; Kwiatkowski, Dominic P; Teo, Yik-Ying

2013-06-06

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

Central sensitization and neuropathic features of ongoing pain in a rat model of advanced osteoarthritis

PubMed Central

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2015-01-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with NSAIDs. The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain while a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present studies, palpation of the ipsilateral hindlimb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced FOS expression in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways by microinjection of lidocaine within the rostral ventromedial medulla (RVM) induced conditioned place preference (CPP) selectively in rats treated with the high dose of MIA. CPP to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, i.p. at −30 min). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that may guide drug discovery for treatment of advanced OA pain without the need for joint replacement. PMID:26694132

Group crisis intervention for children during ongoing war conflict.

PubMed

Thabet, Abdel Aziz; Vostanis, Panos; Karim, Khalid

2005-08-01

The aim of this study was to evaluate the short-term impact of a group crisis intervention for children aged 9-15 years from five refugee camps in the Gaza Strip during ongoing war conflict. Children were selected if they reported moderate to severe posttraumatic stress reactions, and were allocated to group intervention (N=47) encouraging expression of experiences and emotions through storytelling, drawing, free play and role-play; education about symptoms (N=22); or no intervention (N=42). Children completed the CPTSD-RI and the CDI pre- and post-intervention. No significant impact of the group intervention was established on children's posttraumatic or depressive symptoms. Possible explanations of the findings are discussed, including the continuing exposure to trauma and the non-active nature of the intervention.

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

PubMed

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

2018-01-01

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

De novo transcriptome assembly and positive selection analysis of an individual deep-sea fish.

PubMed

Lan, Yi; Sun, Jin; Xu, Ting; Chen, Chong; Tian, Renmao; Qiu, Jian-Wen; Qian, Pei-Yuan

2018-05-24

High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives. We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod. Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies.

Positive and purifying selection in mitochondrial genomes of a bird with mitonuclear discordance.

PubMed

Morales, Hernán E; Pavlova, Alexandra; Joseph, Leo; Sunnucks, Paul

2015-06-01

Diversifying selection on metabolic pathways can reduce intraspecific gene flow and promote population divergence. An opportunity to explore this arises from mitonuclear discordance observed in an Australian bird Eopsaltria australis. Across >1500 km, nuclear differentiation is low and latitudinally structured by isolation by distance, whereas two highly divergent, parapatric mitochondrial lineages (>6.6% in ND2) show a discordant longitudinal geographic pattern and experience different climates. Vicariance, incomplete lineage sorting and sex-biased dispersal were shown earlier to be unlikely drivers of the mitonuclear discordance; instead, natural selection on a female-linked trait was the preferred hypothesis. Accordingly, here we tested for signals of positive, divergent selection on mitochondrial genes in E. australis. We used codon models and physicochemical profiles of amino acid replacements to analyse complete mitochondrial genomes of the two mitochondrial lineages in E. australis, its sister species Eopsaltria griseogularis, and outgroups. We found evidence of positive selection on at least five amino acids, encoded by genes of two oxidative phosphorylation pathway complexes NADH dehydrogenase (ND4 and ND4L) and cytochrome bc1 (cyt-b) against a background of widespread purifying selection on all mitochondrial genes. Three of these amino acid replacements were fixed in ND4 of the geographically most widespread E. australis lineage. The other two replacements were fixed in ND4L and cyt-b of the geographically more restricted E. australis lineage. We discuss whether this selection may reflect local environmental adaptation, a by-product of other selective processes, or genetic incompatibilities, and propose how these hypotheses can be tested in future. © 2015 John Wiley & Sons Ltd.

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

Ongoing Fixed Wing Research within the NASA Langley Aeroelasticity Branch

NASA Technical Reports Server (NTRS)

Bartels, Robert; Chwalowski, Pawel; Funk, Christie; Heeg, Jennifer; Hur, Jiyoung; Sanetrik, Mark; Scott, Robert; Silva, Walter; Stanford, Bret; Wiseman, Carol

2015-01-01

The NASA Langley Aeroelasticity Branch is involved in a number of research programs related to fixed wing aeroelasticity and aeroservoelasticity. These ongoing efforts are summarized here, and include aeroelastic tailoring of subsonic transport wing structures, experimental and numerical assessment of truss-braced wing flutter and limit cycle oscillations, and numerical modeling of high speed civil transport configurations. Efforts devoted to verification, validation, and uncertainty quantification of aeroelastic physics in a workshop setting are also discussed. The feasibility of certain future civil transport configurations will depend on the ability to understand and control complex aeroelastic phenomena, a goal that the Aeroelasticity Branch is well-positioned to contribute through these programs.

Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

PubMed Central

Thut, Gregor; Bergmann, Til Ole; Fröhlich, Flavio; Soekadar, Surjo R.; Brittain, John-Stuart; Valero-Cabré, Antoni; Sack, Alexander; Miniussi, Carlo; Antal, Andrea; Siebner, Hartwig Roman; Ziemann, Ulf; Herrmann, Christoph S.

2017-01-01

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges. PMID:28233641

Evidence of positive selection associated with placental loss in tiger sharks.

PubMed

Swift, Dominic G; Dunning, Luke T; Igea, Javier; Brooks, Edward J; Jones, Catherine S; Noble, Leslie R; Ciezarek, Adam; Humble, Emily; Savolainen, Vincent

2016-06-14

All vertebrates initially feed their offspring using yolk reserves. In some live-bearing species these yolk reserves may be supplemented with extra nutrition via a placenta. Sharks belonging to the Carcharhinidae family are all live-bearing, and with the exception of the tiger shark (Galeocerdo cuvier), develop placental connections after exhausting yolk reserves. Phylogenetic relationships suggest the lack of placenta in tiger sharks is due to secondary loss. This represents a dramatic shift in reproductive strategy, and is likely to have left a molecular footprint of positive selection within the genome. We sequenced the transcriptome of the tiger shark and eight other live-bearing shark species. From this data we constructed a time-calibrated phylogenetic tree estimating the tiger shark lineage diverged from the placental carcharhinids approximately 94 million years ago. Along the tiger shark lineage, we identified five genes exhibiting a signature of positive selection. Four of these genes have functions likely associated with brain development (YWHAE and ARL6IP5) and sexual reproduction (VAMP4 and TCTEX1D2). Our results indicate the loss of placenta in tiger sharks may be associated with subsequent adaptive changes in brain development and sperm production.

BAPJ69-4A: a yeast two-hybrid strain for both positive and negative genetic selection.

PubMed

Shaffer, Hally Anne; Rood, Michael Kenneth; Kashlan, Badar; Chang, Eileen I-ling; Doyle, Donald Francis; Azizi, Bahareh

2012-10-01

Genetic selection systems, such as the yeast two-hybrid system, are efficient methods to detect protein-protein and protein-ligand interactions. These systems have been further developed to assess negative interactions, such as inhibition, using the URA3 genetic selection marker. Previously, chemical complementation was used to assess positive selection in Saccharomyces cerevisiae. In this work, a new S. cerevisiae strain, called BAPJ69-4A, containing three selective markers ADE2, HIS3, and URA3 as well as the lacZ gene controlled by Gal4 response elements, was developed and characterized using the retinoid X receptor (RXR) and its ligand 9-cis retinoic acid (9cRA). Further characterization was performed using RXR variants and the synthetic ligand LG335. To assess the functionality of the strain, RXR was compared to the parent strain PJ69-4A in adenine, histidine, and uracil selective media. In positive selection, associating partners that lead to cell growth were observed in all media in the presence of ligand, whereas partners that did not associate due to the absence of ligand displayed no growth. Conversely, in negative selection, partners that did not associate in 5-FOA medium did not display cell death due to the lack of expression of the URA3 gene. The creation of the BAPJ69-4A yeast strain provides a high-throughput selection system, called negative chemical complementation, which can be used for both positive and negative selection, providing a fast, powerful tool for discovering novel ligand receptor pairs for applications in drug discovery and protein engineering. Copyright © 2012 Elsevier B.V. All rights reserved.

A new method for selecting auricle positions in skull base reconstruction for temporal bone cancer.

PubMed

Tanaka, Kentaro; Yano, Tomoyuki; Homma, Tsutomu; Tsunoda, Atsunobu; Aoyagi, Masaru; Kishimoto, Seiji; Okazaki, Mutsumi

2018-03-25

In advanced temporal bone carcinoma cases, we attempted to preserve as much of the auricle as possible from a cosmetic and functional perspective. Difficulties are associated with selecting an adequate position for reconstructed auricles intraoperatively. We improved the surgical procedure to achieve a good postoperative auricle position. Nine patients were included in this study. All patients underwent subtotal removal of the temporal bone and resection of the external auditory canal while preserving most of the external ear, and lateral skull base reconstruction was performed with anterolateral thigh flaps. We invented a new device, the auricle localizer, to select the correct position for the replaced external ear. The head skin incision line and two points of three-point pin fixation were used as criteria, and a Kirschner wire was shaped as a basic line to match these criteria. Another Kirschner wire was shaped by wrapping it around the inferior edge of the external ear as the positioning line, and these two lines were then combined. To evaluate the postoperative auricle position, the auricle inclination angle was measured using head frontal cephalogram imaging. The external ear on the affected side clearly drooped postoperatively in nonlocalizer cases, whereas this was not obvious in localizer cases. Auricle inclination angles 1 year after surgery significantly differed between these two cases (P = 0.018). The surgical device, the auricle localizer, is useful for selecting intraoperative accurate auricle positions. The assessment index, the auricle inclination angle, is useful for quantitatively evaluating postoperative results. 4 Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Evidence of recombination and positive selection in cetacean papillomaviruses.

PubMed

Robles-Sikisaka, Refugio; Rivera, Rebecca; Nollens, Hendrik H; St Leger, Judy; Durden, Wendy N; Stolen, Megan; Burchell, Jennifer; Wellehan, James F X

2012-06-05

Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution. Copyright © 2012 Elsevier Inc. All rights reserved.

Evidence of recombination and positive selection in cetacean papillomaviruses

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

Robles-Sikisaka, Refugio, E-mail: refugio.robles1@gmail.com; Rivera, Rebecca, E-mail: RRivera@hswri.org; Nollens, Hendrik H., E-mail: Hendrik.Nollens@SeaWorld.com

2012-06-05

Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 genemore » did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.« less

Detecting Signatures of Positive Selection along Defined Branches of a Population Tree Using LSD.

PubMed

Librado, Pablo; Orlando, Ludovic

2018-06-01

Identifying the genomic basis underlying local adaptation is paramount to evolutionary biology, and bears many applications in the fields of conservation biology, crop, and animal breeding, as well as personalized medicine. Although many approaches have been developed to detect signatures of positive selection within single populations and population pairs, the increasing wealth of high-throughput sequencing data requires improved methods capable of handling multiple, and ideally large number of, populations in a single analysis. In this study, we introduce LSD (levels of exclusively shared differences), a fast and flexible framework to perform genome-wide selection scans, along the internal and external branches of a given population tree. We use forward simulations to demonstrate that LSD can identify branches targeted by positive selection with remarkable sensitivity and specificity. We illustrate a range of potential applications by analyzing data from the 1000 Genomes Project and uncover a list of adaptive candidates accompanying the expansion of anatomically modern humans out of Africa and their spread to Europe.

Ongoing training of community health workers in low-income and middle-income countries: a systematic scoping review of the literature

PubMed Central

O’Donovan, Charles; Kuhn, Isla; Sachs, Sonia Ehrlich

2018-01-01

Objectives Understanding the current landscape of ongoing training for community health workers (CHWs) in low-income and middle-income countries (LMICs) is important both for organisations responsible for their training, as well as researchers and policy makers. This scoping review explores this under-researched area by mapping the current delivery implementation and evaluation of ongoing training provision for CHWs in LMICs. Design Systematic scoping review. Data sources MEDLINE, Embase, AMED, Global Health, Web of Science, Scopus, ASSIA, LILACS, BEI and ERIC. Study selection Original studies focusing on the provision of ongoing training for CHWs working in a country defined as low income and middle income according to World Bank Group 2012 classification of economies. Results The scoping review found 35 original studies that met the inclusion criteria. Ongoing training activities for CHWs were described as supervision (n=19), inservice or refresher training (n=13) or a mixture of both (n=3). Although the majority of studies emphasised the importance of providing ongoing training, several studies reported no impact of ongoing training on performance indicators. The majority of ongoing training was delivered inperson; however, four studies reported the use of mobile technologies to support training delivery. The outcomes from ongoing training activities were measured and reported in different ways, including changes in behaviour, attitudes and practice measured in a quantitative manner (n=16), knowledge and skills (n=6), qualitative assessments (n=5) or a mixed methods approach combining one of the aforementioned modalities (n=8). Conclusions This scoping review highlights the diverse range of ongoing training for CHWs in LMICs. Given the expansion of CHW programmes globally, more attention should be given to the design, delivery, monitoring and sustainability of ongoing training from a health systems strengthening perspective. PMID:29705769

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

PubMed

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2016-03-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

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

B Pan; Y Xiong; T Steitz

2011-12-31

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3' end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5'-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5'-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3' hydroxyl group of cytidine75.« less

Positive Selection Driving Cytoplasmic Genome Evolution of the Medicinally Important Ginseng Plant Genus Panax.

PubMed

Jiang, Peng; Shi, Feng-Xue; Li, Ming-Rui; Liu, Bao; Wen, Jun; Xiao, Hong-Xing; Li, Lin-Feng

2018-01-01

Panax L. (the ginseng genus) is a shade-demanding group within the family Araliaceae and all of its species are of crucial significance in traditional Chinese medicine. Phylogenetic and biogeographic analyses demonstrated that two rounds of whole genome duplications accompanying with geographic and ecological isolations promoted the diversification of Panax species. However, contributions of the cytoplasmic genomes to the adaptive evolution of Panax species remained largely uninvestigated. In this study, we sequenced the chloroplast and mitochondrial genomes of 11 accessions belonging to seven Panax species. Our results show that heterogeneity in nucleotide substitution rate is abundant in both of the two cytoplasmic genomes, with the mitochondrial genome possessing more variants at the total level but the chloroplast showing higher sequence polymorphisms at the genic regions. Genome-wide scanning of positive selection identified five and 12 genes from the chloroplast and mitochondrial genomes, respectively. Functional analyses further revealed that these selected genes play important roles in plant development, cellular metabolism and adaptation. We therefore conclude that positive selection might be one of the potential evolutionary forces that shaped nucleotide variation pattern of these Panax species. In particular, the mitochondrial genes evolved under stronger selective pressure compared to the chloroplast genes.

Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions.

PubMed

Spring, Laura; Bardia, Aditya; Modi, Shanu

2016-01-01

Dysregulation of the cyclin D-cyclin-dependent kinase (CDK) 4/6-INK4-retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively non-selective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in ER+ breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicated promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II-III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the rationale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combination strategies with CDK 4/6 backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with ER+ breast cancer.

Properties of different selection signature statistics and a new strategy for combining them.

PubMed

Ma, Y; Ding, X; Qanbari, S; Weigend, S; Zhang, Q; Simianer, H

2015-11-01

Identifying signatures of recent or ongoing selection is of high relevance in livestock population genomics. From a statistical perspective, determining a proper testing procedure and combining various test statistics is challenging. On the basis of extensive simulations in this study, we discuss the statistical properties of eight different established selection signature statistics. In the considered scenario, we show that a reasonable power to detect selection signatures is achieved with high marker density (>1 SNP/kb) as obtained from sequencing, while rather small sample sizes (~15 diploid individuals) appear to be sufficient. Most selection signature statistics such as composite likelihood ratio and cross population extended haplotype homozogysity have the highest power when fixation of the selected allele is reached, while integrated haplotype score has the highest power when selection is ongoing. We suggest a novel strategy, called de-correlated composite of multiple signals (DCMS) to combine different statistics for detecting selection signatures while accounting for the correlation between the different selection signature statistics. When examined with simulated data, DCMS consistently has a higher power than most of the single statistics and shows a reliable positional resolution. We illustrate the new statistic to the established selective sweep around the lactase gene in human HapMap data providing further evidence of the reliability of this new statistic. Then, we apply it to scan selection signatures in two chicken samples with diverse skin color. Our analysis suggests that a set of well-known genes such as BCO2, MC1R, ASIP and TYR were involved in the divergent selection for this trait.

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

PubMed Central

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

2006-01-01

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

Transcriptome Sequencing of Lima Bean (Phaseolus lunatus) to Identify Putative Positive Selection in Phaseolus and Legumes

PubMed Central

Li, Fengqi; Cao, Depan; Liu, Yang; Yang, Ting; Wang, Guirong

2015-01-01

The identification of genes under positive selection is a central goal of evolutionary biology. Many legume species, including Phaseolus vulgaris (common bean) and Phaseolus lunatus (lima bean), have important ecological and economic value. In this study, we sequenced and assembled the transcriptome of one Phaseolus species, lima bean. A comparison with the genomes of six other legume species, including the common bean, Medicago, lotus, soybean, chickpea, and pigeonpea, revealed 15 and 4 orthologous groups with signatures of positive selection among the two Phaseolus species and among the seven legume species, respectively. Characterization of these positively selected genes using Non redundant (nr) annotation, gene ontology (GO) classification, GO term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these genes are mostly involved in thylakoids, photosynthesis and metabolism. This study identified genes that may be related to the divergence of the Phaseolus and legume species. These detected genes are particularly good candidates for subsequent functional studies. PMID:26151849

Duration of blastulation may be associated with ongoing pregnancy rate in single euploid blastocyst transfer cycles.

PubMed

Mumusoglu, Sezcan; Ozbek, Irem Y; Sokmensuer, Lale K; Polat, Mehtap; Bozdag, Gurkan; Papanikolaou, Evangelos; Yarali, Hakan

2017-12-01

Not all euploid embryos implant, necessitating additional tools to select viable blastocysts in preimplantation genetic screening cycles. In this retrospective cohort study, 129 consecutive patients who underwent 129 single euploid blastocyst transfers in cryopreserved embryo transfer cycles were included. All embryos were individually cultured in a time-lapse incubator from intracytoplasmic sperm injection up to trophoectoderm biopsy. Twenty-three time-lapse morphokinetic variables were tested among patients with (n = 68) or without (n = 61) ongoing pregnancy. All 23 time-lapse morphokinetic variables, apart from duration of blastulation (tB-tSB), were comparable between patients with or without ongoing pregnancy. Duration of blastulation was significantly shorter in patients with ongoing pregnancy (8.1 ± 3.2 versus 9.5 ± 3.4 h; P = 0.014); shorter duration of blastulation remained an independent predictor for ongoing pregnancy, when tested by logistic regression analysis (OR 0.81; 95% CI 0.70 to 0.93). One important limitation of this study, and a reason for caution, is the use of multiple comparisons, which can lead to differences at the 0.05 level simply by chance or random variation. Nonetheless, the study suggests that when more than one euploid blastocyst is available, priority might be given to those with a shorter duration of blastulation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Investigation of some selected strategies for multi-GNSS instantaneous RTK positioning

NASA Astrophysics Data System (ADS)

Paziewski, Jacek; Wielgosz, Pawel

2017-01-01

It is clear that we can benefit from multi-constellation GNSS in precise relative positioning. On the other hand, it is still an open problem how to combine multi-GNSS signals in a single functional model. This study presents methodology and quality assessment of selected methods allowing for multi-GNSS observations combining in relative kinematic positioning using baselines up to tens of kilometers. In specific, this paper characterizes loose and tight integration strategies applied to the ionosphere and troposphere weighted model. Performance assessment of the established strategies was based on the analyses of the integer ambiguity resolution and rover coordinates' repeatability obtained in the medium range instantaneous RTK positioning with the use of full constellation dual frequency GPS and Galileo signals. Since full constellation of Galileo satellites is not yet available, the observational data were obtained from a hardware GNSS signal simulator using regular geodetic GNSS receivers. The results indicate on similar and high performance of the loose, and tight integration with calibrated receiver ISBs strategies. These approaches have undeniable advantage over single system positioning in terms of reliability of the integer ambiguity resolution as well as rover coordinate repeatability.

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan

PubMed Central

Görlach, Matthias; Müller, Christine; Schwab, Matthias; Kraus, Johann; Cellerino, Alessandro; Hildebrandt, Thomas

2018-01-01

The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were “cellular respiration” and “metal ion homeostasis”, as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination. PMID:29570707

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan.

PubMed

Sahm, Arne; Bens, Martin; Szafranski, Karol; Holtze, Susanne; Groth, Marco; Görlach, Matthias; Calkhoven, Cornelis; Müller, Christine; Schwab, Matthias; Kraus, Johann; Kestler, Hans A; Cellerino, Alessandro; Burda, Hynek; Hildebrandt, Thomas; Dammann, Philip; Platzer, Matthias

2018-03-01

The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were "cellular respiration" and "metal ion homeostasis", as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination.

Positive selection on panpulmonate mitogenomes provide new clues on adaptations to terrestrial life.

PubMed

Romero, Pedro E; Weigand, Alexander M; Pfenninger, Markus

2016-08-22

Transitions from marine to intertidal and terrestrial habitats resulted in a significant adaptive radiation within the Panpulmonata (Gastropoda: Heterobranchia). This clade comprises several groups that invaded the land realm independently and in different time periods, e.g., Ellobioidea, Systellomatophora, and Stylommatophora. Thus, mitochondrial genomes of panpulmonate gastropods are promising to screen for adaptive molecular signatures related to land invasions. We obtained three complete mitochondrial genomes of terrestrial panpulmonates, i.e., the ellobiid Carychium tridentatum, and the stylommatophorans Arion rufus and Helicella itala. Our dataset consisted of 50 mitogenomes comprising almost all major panpulmonate lineages. The phylogenetic tree based on mitochondrial genes supports the monophyly of the clade Panpulmonata. Terrestrial lineages were sampled from Ellobioidea (1 sp.) and Stylommatophora (9 spp.). The branch-site test of positive selection detected significant non-synonymous changes in the terrestrial branches leading to Carychium (Ellobiodea) and Stylommatophora. These convergent changes occurred in the cob and nad5 genes (OXPHOS complex III and I, respectively). The convergence of the non-synonymous changes in cob and nad5 suggest possible ancient episodes of positive selection related to adaptations to non-marine habitats. The positively selected sites in our data are in agreement with previous results in vertebrates suggesting a general pattern of adaptation to the new metabolic requirements. The demand for energy due to the colonization of land (for example, to move and sustain the body mass in the new habitat) and the necessity to tolerate new conditions of abiotic stress may have changed the physiological constraints in the early terrestrial panpulmonates and triggered adaptations at the mitochondrial level.

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

PubMed Central

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

2006-01-01

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

Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity.

PubMed

Natsubori, Akiyo; Tsutsui-Kimura, Iku; Nishida, Hiroshi; Bouchekioua, Youcef; Sekiya, Hiroshi; Uchigashima, Motokazu; Watanabe, Masahiko; de Kerchove d'Exaerde, Alban; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F

2017-03-08

The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca 2+ indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca 2+ elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior. SIGNIFICANCE STATEMENT An opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has

Evolution of CCL11: genetic characterization in lagomorphs and evidence of positive and purifying selection in mammals.

PubMed

Neves, Fabiana; Abrantes, Joana; Esteves, Pedro J

2016-07-01

The interactions between chemokines and their receptors are crucial for differentiation and activation of inflammatory cells. CC chemokine ligand 11 (CCL11) binds to CCR3 and to CCR5 that in leporids underwent gene conversion with CCR2. Here, we genetically characterized CCL11 in lagomorphs (leporids and pikas). All lagomorphs have a potentially functional CCL11, and the Pygmy rabbit has a mutation in the stop codon that leads to a longer protein. Other mammals also have mutations at the stop codon that result in proteins with different lengths. By employing maximum likelihood methods, we observed that, in mammals, CCL11 exhibits both signatures of purifying and positive selection. Signatures of purifying selection were detected in sites important for receptor binding and activation. Of the three sites detected as under positive selection, two were located close to the stop codon. Our results suggest that CCL11 is functional in all lagomorphs, and that the signatures of purifying and positive selection in mammalian CCL11 probably reflect the protein's biological roles. © The Author(s) 2016.

Positive Selection Driving Cytoplasmic Genome Evolution of the Medicinally Important Ginseng Plant Genus Panax

PubMed Central

Jiang, Peng; Shi, Feng-Xue; Li, Ming-Rui; Liu, Bao; Wen, Jun; Xiao, Hong-Xing; Li, Lin-Feng

2018-01-01

Panax L. (the ginseng genus) is a shade-demanding group within the family Araliaceae and all of its species are of crucial significance in traditional Chinese medicine. Phylogenetic and biogeographic analyses demonstrated that two rounds of whole genome duplications accompanying with geographic and ecological isolations promoted the diversification of Panax species. However, contributions of the cytoplasmic genomes to the adaptive evolution of Panax species remained largely uninvestigated. In this study, we sequenced the chloroplast and mitochondrial genomes of 11 accessions belonging to seven Panax species. Our results show that heterogeneity in nucleotide substitution rate is abundant in both of the two cytoplasmic genomes, with the mitochondrial genome possessing more variants at the total level but the chloroplast showing higher sequence polymorphisms at the genic regions. Genome-wide scanning of positive selection identified five and 12 genes from the chloroplast and mitochondrial genomes, respectively. Functional analyses further revealed that these selected genes play important roles in plant development, cellular metabolism and adaptation. We therefore conclude that positive selection might be one of the potential evolutionary forces that shaped nucleotide variation pattern of these Panax species. In particular, the mitochondrial genes evolved under stronger selective pressure compared to the chloroplast genes. PMID:29670636

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

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

Pan, Baocheng; Xiong, Yong; Steitz, Thomas A.

2010-11-22

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3{prime} end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5{prime}-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5{prime}-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3{prime} hydroxyl group of cytidine75.« less

Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

PubMed Central

2012-01-01

Background Reducing low-density lipoprotein cholesterol (LDL-C) is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83) to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg) or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg) for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026) and total cholesterol (20.8% vs 12.2%, p = 0.0003). Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6%) vs doubling statin (41.2%), but the difference was not statistically significant (p = 0.1675). The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327 PMID:22621316

Conserved hypothetical protein Rv1977 in Mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion.

PubMed

Jiang, Yi; Liu, Haican; Wang, Xuezhi; Li, Guilian; Qiu, Yan; Dou, Xiangfeng; Wan, Kanglin

2015-01-01

Host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. A previous study showed that human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 151 clinical Mycobacterium tuberculosis isolates from China, amplified gene encoding Rv1977 and compared the sequences. The results showed that Rv1977, a conserved hypothetical protein, is not conserved in M. tuberculosis strains and there are polymorphisms existed in the protein. Some mutations, especially one frameshift mutation, occurred in the antigen Rv1977, which is uncommon in M.tb strains and may lead to the protein function altering. Mutations and deletion in the gene all affect one of three T cell epitopes and the changed T cell epitope contained more than one variable position, which may suggest ongoing immune evasion.

Transcriptome-based phylogeny of endemic Lake Baikal amphipod species flock: fast speciation accompanied by frequent episodes of positive selection.

PubMed

Naumenko, Sergey A; Logacheva, Maria D; Popova, Nina V; Klepikova, Anna V; Penin, Aleksey A; Bazykin, Georgii A; Etingova, Anna E; Mugue, Nikolai S; Kondrashov, Alexey S; Yampolsky, Lev Y

2017-01-01

Endemic species flocks inhabiting ancient lakes, oceanic islands and other long-lived isolated habitats are often interpreted as adaptive radiations. Yet molecular evidence for directional selection during species flocks radiation is scarce. Using partial transcriptomes of 64 species of Lake Baikal (Siberia, Russia) endemic amphipods and two nonendemic outgroups, we report a revised phylogeny of this species flock and analyse evidence for positive selection within the endemic lineages. We confirm two independent invasions of amphipods into Baikal and demonstrate that several morphological features of Baikal amphipods, such as body armour and reduction in appendages and sensory organs, evolved in several lineages in parallel. Radiation of Baikal amphipods has been characterized by short phylogenetic branches and frequent episodes of positive selection which tended to be more frequent in the early phase of the second invasion of amphipods into Baikal when the most intensive diversification occurred. Notably, signatures of positive selection are frequent in genes encoding mitochondrial membrane proteins with electron transfer chain and ATP synthesis functionality. In particular, subunits of both the membrane and substrate-level ATP synthases show evidence of positive selection in the plankton species Macrohectopus branickii, possibly indicating adaptation to active plankton lifestyle and to survival under conditions of low temperature and high hydrostatic pressures known to affect membranes functioning. Other functional categories represented among genes likely to be under positive selection include Ca-binding muscle-related proteins, possibly indicating adaptation to Ca-deficient low mineralization Baikal waters. © 2016 John Wiley & Sons Ltd.

'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism.

PubMed

Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

2015-09-18

Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans.

Afferent Drive Elicits Ongoing Pain in a Model of Advanced Osteoarthritis

PubMed Central

Okun, Alec; Liu, Ping; Davis, Peg; Ren, Jiyang; Remeniuk, Bethany; Brion, Triza; Ossipov, Michael H.; Xie, Jennifer; Dussor, Gregory O.; King, Tamara; Porreca, Frank

2012-01-01

Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience pain at rest (i.e., ongoing pain)that is generally resistant to non-steroidal anti-inflammatory drugs (NSAIDs). Injection of monosodium iodoacetate (MIA) into the intra-articular space of the rodent knee is a well-established model of OA that elicits weight-bearing asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain is present in this model is unknown. Additionally, the possible relationship of ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg). However, only rats treated with the highest dose of MIA showed conditioned place preference to a context paired with intra-articular lidocaine, indicating relief from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed to block MIA-induced ongoing pain. Systemic AMG9810, a TRPV1 antagonist, effectively blocked thermal hypersensitivity, but failed to block high dose MIA-induced weight asymmetry or ongoing pain. Additionally, systemic or intra-articular HC030031, a TRPA1 antagonist, failed to block high dose MIA-induced weight asymmetry or ongoing pain. Our studies suggest that a high dose of intra-articular MIA induces ongoing pain originating from the site of injury that is dependent on afferent fiber activity but apparently independent of TRPV1 or TRPA1 activation. Identification of mechanisms driving ongoing pain may enable development of improved treatments for patients with severe OA pain and diminish the need for joint replacement surgery. PMID:22387095

Social gating of sensory information during ongoing communication.

PubMed

Anders, Silke; Heussen, Yana; Sprenger, Andreas; Haynes, John-Dylan; Ethofer, Thomas

2015-01-01

Social context plays an important role in human communication. Depending on the nature of the source, the same communication signal might be processed in fundamentally different ways. However, the selective modulation (or "gating") of the flow of neural information during communication is not fully understood. Here, we use multivoxel pattern analysis (MVPA) and multivoxel connectivity analysis (MVCA), a novel technique that allows to analyse context-dependent changes of the strength interregional coupling between ensembles of voxels, to examine how the human brain differentially gates content-specific sensory information during ongoing perception of communication signals. In a simulated electronic communication experiment, participants received two alternative text messages during fMRI ("happy" or "sad") which they believed had been sent either by their real-life friend outside the scanner or by a computer. A region in the dorsal medial prefrontal cortex (dmPFC) selectively increased its functional coupling with sensory-content encoding regions in the visual cortex when a text message was perceived as being sent by the participant's friend, and decreased its functional coupling with these regions when a text message was perceived as being sent by the computer. Furthermore, the strength of neural encoding of content-specific information of text messages in the dmPFC was modulated by the social tie between the participant and her friend: the more of her spare time a participant reported to spend with her friend the stronger was the neural encoding. This suggests that the human brain selectively gates sensory information into the relevant network for processing the mental states of others, depending on the source of the communication signal. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication.

PubMed

Wang, Ming-Shan; Zhang, Rong-Wei; Su, Ling-Yan; Li, Yan; Peng, Min-Sheng; Liu, He-Qun; Zeng, Lin; Irwin, David M; Du, Jiu-Lin; Yao, Yong-Gang; Wu, Dong-Dong; Zhang, Ya-Ping

2016-05-01

As noted by Darwin, chickens have the greatest phenotypic diversity of all birds, but an interesting evolutionary difference between domestic chickens and their wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing theories suggest that diminished visual prowess among domestic chickens reflect changes driven by the relaxation of functional constraints on vision, but the evidence identifying the underlying genetic mechanisms responsible for this change has not been definitively characterized. Here, a genome-wide analysis of the domestic chicken and Red Junglefowl genomes showed significant enrichment for positively selected genes involved in the development of vision. There were significant differences between domestic chickens and their wild ancestors regarding the level of mRNA expression for these genes in the retina. Numerous additional genes involved in the development of vision also showed significant differences in mRNA expression between domestic chickens and their wild ancestors, particularly for genes associated with phototransduction and photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3. Finally, we characterized the potential role of the VIT gene in vision, which experienced positive selection and downregulated expression in the retina of the village chicken. Overall, our results suggest that positive selection, rather than relaxation of purifying selection, contributed to the evolution of vision in domestic chickens. The progenitors of domestic chickens harboring weaker vision may have showed a reduced fear response and vigilance, making them easier to be unconsciously selected and/or domesticated.

Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication

PubMed Central

Wang, Ming-Shan; Zhang, Rong-wei; Su, Ling-Yan; Li, Yan; Peng, Min-Sheng; Liu, He-Qun; Zeng, Lin; Irwin, David M; Du, Jiu-Lin; Yao, Yong-Gang; Wu, Dong-Dong; Zhang, Ya-Ping

2016-01-01

As noted by Darwin, chickens have the greatest phenotypic diversity of all birds, but an interesting evolutionary difference between domestic chickens and their wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing theories suggest that diminished visual prowess among domestic chickens reflect changes driven by the relaxation of functional constraints on vision, but the evidence identifying the underlying genetic mechanisms responsible for this change has not been definitively characterized. Here, a genome-wide analysis of the domestic chicken and Red Junglefowl genomes showed significant enrichment for positively selected genes involved in the development of vision. There were significant differences between domestic chickens and their wild ancestors regarding the level of mRNA expression for these genes in the retina. Numerous additional genes involved in the development of vision also showed significant differences in mRNA expression between domestic chickens and their wild ancestors, particularly for genes associated with phototransduction and photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3. Finally, we characterized the potential role of the VIT gene in vision, which experienced positive selection and downregulated expression in the retina of the village chicken. Overall, our results suggest that positive selection, rather than relaxation of purifying selection, contributed to the evolution of vision in domestic chickens. The progenitors of domestic chickens harboring weaker vision may have showed a reduced fear response and vigilance, making them easier to be unconsciously selected and/or domesticated. PMID:27033669

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2000-03-01

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

Effectiveness of an Ongoing, Community-Based Breast Cancer Prevention Program for Korean American Women.

PubMed

Koh, Eun; Choi, Ga-Young; Cho, Ji Young

2016-02-01

The study evaluates the effectiveness of an ongoing, community-based breast cancer prevention program offered by a local social services agency in the Washington, DC, metropolitan area. Korean American women who participated in this breast cancer prevention program were compared with those who did not participate in their knowledge, attitude, and screening behaviors. The study found that the intervention group was more knowledgeable on breast cancer and related services and reported more positive attitudes toward breast cancer screening services than the comparison group. The participants in the intervention group were also more likely to plan to receive a mammogram than those in the comparison group. However, significant differences were not observed in the two groups in their intention to receive a clinical breast examination. The study findings suggest that an ongoing, community-based breast cancer prevention program can be an effective method of addressing breast cancer prevention disparities observed among Korean American women.

Factors associated with ongoing criminal engagement while in opioid maintenance treatment.

PubMed

Stavseth, Marianne Riksheim; Røislien, Jo; Bukten, Anne; Clausen, Thomas

2017-06-01

This study examines factors associated with criminal engagement among patients in opioid maintenance treatment (OMT). Questionnaire data recorded annually among 5654 patients in the Norwegian OMT programme between 2005 and 2010 from seven regional treatment centres were available for analyses. Each patient answered approximately 4 times (mean: 4.11, SD: 1.46) generating a total of 18,538 questionnaires. The outcome variable of the study, engagement in criminal activity, was defined as whether a patient had been arrested, put in custody, been charged and/or convicted of a crime within the last 12months prior to the completion of the questionnaire. Three types of covariates were included: demographical, psychosocial and drug use-related. Missing data were imputed using Multivariate Imputation by Chained Equations and regression parameters were estimated by Generalized Estimation Equations to account for correlated measurements. Having a full-time job (aOR: 0.47, CI: 0.34-0.64) or being a student/having a part-time job (aOR: 0.72, CI: 0.59-0.88) was negatively associated with ongoing criminal involvement, as did having a stable living situation (aOR: 0.70, CI: 0.57-0.87). On the other hand, being male (aOR: 1.83, CI: 1.59-2.10), younger (aOR: 0.96, CI: 0.95-0.97) and using illicit drugs regularly (aOR: 3.00, CI: 2.56-3.52) was positively associated with ongoing criminal activity while in OMT. Stable accommodation and participation in meaningful daily activity was found to be protective in terms of ongoing criminal engagement. Focus on these modifiable, psychosocial factors should therefore be an important and integral aspect of opioid maintenance treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Ongoing Voluntary Settlement and Independent Agency: Evidence from China

PubMed Central

Feng, Jing; Ren, Xiaopeng; Ma, Xinran

2017-01-01

Voluntary frontier settlement leads to independent agency. Since this type of research has not yet been implemented in ongoing voluntary settlement frontiers, we conducted several cultural tasks to investigate Shenzhen, known as China’s ongoing “South Frontier,” which is composed mostly of people that have emigrated from other Chinese provinces within the past 30 years. We hypothesized that residents of Shenzhen are more independent than those in other regions of Mainland China. As predicted, residents of Shenzhen scored higher than China inland residents in self-reported independent beliefs and scored lower in nepotism. The results indicate that, even in a short-term ongoing frontier, voluntary settlement is associated with independent agency. PMID:28798712

Inhibition of ongoing responses in patients with Parkinson's disease

PubMed Central

Gauggel, S; Rieger, M; Feghoff, T

2004-01-01

Objectives: We investigated the involvement of the basal ganglia in inhibiting ongoing responses in patients with Parkinson's disease (PD). Methods: Thirty two patients with PD and 31 orthopaedic controls performed the stop signal task, which allows an estimation of the time it takes to inhibit an ongoing reaction (stop signal reaction time, SSRT). Results: Patients with PD showed significantly longer SSRTs than the controls. This effect seemed to be independent of global cognitive impairment and severity of PD. Furthermore, in the PD patients, there was no significant relation between general slowing and inhibitory efficiency. Conclusions: Our results provide evidence for involvement of the basal ganglia in the inhibition of ongoing responses. PMID:15026491

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

PubMed Central

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

2009-01-01

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

Positive selection of AS3MT to arsenic water in Andean populations

PubMed Central

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

2016-01-01

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

Distinguishing Positive Selection From Neutral Evolution: Boosting the Performance of Summary Statistics

PubMed Central

Lin, Kao; Li, Haipeng; Schlötterer, Christian; Futschik, Andreas

2011-01-01

Summary statistics are widely used in population genetics, but they suffer from the drawback that no simple sufficient summary statistic exists, which captures all information required to distinguish different evolutionary hypotheses. Here, we apply boosting, a recent statistical method that combines simple classification rules to maximize their joint predictive performance. We show that our implementation of boosting has a high power to detect selective sweeps. Demographic events, such as bottlenecks, do not result in a large excess of false positives. A comparison to other neutrality tests shows that our boosting implementation performs well compared to other neutrality tests. Furthermore, we evaluated the relative contribution of different summary statistics to the identification of selection and found that for recent sweeps integrated haplotype homozygosity is very informative whereas older sweeps are better detected by Tajima's π. Overall, Watterson's θ was found to contribute the most information for distinguishing between bottlenecks and selection. PMID:21041556

Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints.

PubMed

Vargas-Pinilla, Pedro; Paixão-Côrtes, Vanessa Rodrigues; Paré, Pamela; Tovo-Rodrigues, Luciana; Vieira, Carlos Meton de Alencar Gadelha; Xavier, Agatha; Comas, David; Pissinatti, Alcides; Sinigaglia, Marialva; Rigo, Maurício Menegatti; Vieira, Gustavo Fioravanti; Lucion, Aldo B; Salzano, Francisco Mauro; Bortolini, Maria Cátira

2015-01-06

Oxytocin is a nonapeptide involved in a wide range of physiologic and behavioral functions. Until recently, it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed oxytocin (OXT) in 29 primate species and the oxytocin receptor (OXTR) in 21 of these species. We report here three novel OXT forms in the New World monkeys, as well as a more extensive distribution of a previously described variant (Leu8Pro). In structural terms, these OXTs share the same three low-energy conformations in solution during molecular dynamic simulations, with subtle differences in their side chains. A consistent signal of positive selection was detected in the Cebidae family, and OXT position 8 showed a statistically significant (P = 0.013) correlation with litter size. Several OXTR changes were identified, some of them promoting gain or loss of putative phosphorylation sites, with possible consequences for receptor internalization and desensitization. OXTR amino acid sites are under positive selection, and intramolecular and intermolecular coevolutionary processes with OXT were also detected. We suggest that some New World monkey OXT-OXTR forms can be correlated to male parental care through the increase of cross-reactivity with its correlated vasopressin system.

Overview of Ongoing NRMRL GI Research

EPA Science Inventory

This presentation is an overview of ongoing NRMRL Green Infrastructure research and addresses the question: What do we need to know to present a cogent estimate of the value of Green Infrastructure? Discussions included are: stormwater well study, rain gardens and permeable su...

Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV Protease Inhibitor Nelfinavir

PubMed Central

2012-01-01

Background Human epidermal growth factor receptor 2 (HER2)–positive breast cancer is highly aggressive and has higher risk of recurrence than HER2-negative cancer. With few treatment options available, new drug targets specific for HER2-positive breast cancer are needed. Methods We conducted a pharmacological profiling of seven genotypically distinct breast cancer cell lines using a subset of inhibitors of breast cancer cells from a screen of the Johns Hopkins Drug Library. To identify molecular targets of nelfinavir, identified in the screen as a selective inhibitor of HER2-positive cells, we conducted a genome-wide screen of a haploinsufficiency yeast mutant collection. We evaluated antitumor activity of nelfinavir with xenografts in athymic nude mouse models (n = 4–6 per group) of human breast cancer and repeated mixed-effects regression analysis. All statistical tests were two-sided. Results Pharmacological profiling showed that nelfinavir, an anti-HIV drug, selectively inhibited the growth of HER2-positive breast cancer cells in vitro. A genome-wide screening of haploinsufficiency yeast mutants revealed that nelfinavir inhibited heat shock protein 90 (HSP90) function. Further characterization using proteolytic footprinting experiments indicated that nelfinavir inhibited HSP90 in breast cancer cells through a novel mechanism. In vivo, nelfinavir selectively inhibited the growth of HER2-positive breast cancer cells (tumor volume index of HCC1954 cells on day 29, vehicle vs nelfinavir, mean = 14.42 vs 5.16, difference = 9.25, 95% confidence interval [CI] = 5.93 to 12.56, P < .001; tumor volume index of BT474 cells on day 26, vehicle vs nelfinavir, mean = 2.21 vs 0.90, difference = 1.31, 95% CI = 0.83 to 1.78, P < .001). Moreover, nelfinavir inhibited the growth of trastuzumab- and/or lapatinib-resistant, HER2-positive breast cancer cells in vitro at clinically achievable concentrations. Conclusion Nelfinavir was found to be a new class of HSP90 inhibitor and

Ongoing Progress in Spacecraft Controls

NASA Technical Reports Server (NTRS)

Ghosh, Dave (Editor)

1992-01-01

This publication is a collection of papers presented at the Mars Mission Research Center workshop on Ongoing Progress in Spacecraft Controls. The technical program addressed additional Mars mission control problems that currently exist in robotic missions in addition to human missions. Topics include control systems design in the presence of large time delays, fuel-optimal propulsive control, and adaptive control to handle a variety of unknown conditions.

Single substitutions to closely related amino acids contribute to the functional diversification of an insect-inducible, positively selected plant cystatin.

PubMed

Rasoolizadeh, Asieh; Goulet, Marie-Claire; Sainsbury, Frank; Cloutier, Conrad; Michaud, Dominique

2016-04-01

A causal link has been reported between positively selected amino acids in plant cystatins and the inhibitory range of these proteins against insect digestive cysteine (Cys) proteases. Here we assessed the impact of single substitutions to closely related amino acids on the contribution of positive selection to cystatin diversification. Cystatin sequence alignments, while confirming hypervariability, indicated a preference for related amino acids at positively selected sites. For example, the non-polar residues leucine (Leu), isoleucine (Ile) and valine (Val) were shown to predominate at positively selected site 2 in the N-terminal region, unlike selected sites 6 and 10, where polar residues are preferred. The model cystatin SlCYS8 and single variants with Leu, Ile or Val at position 2 were compared with regard to their ability to bind digestive proteases of the coleopteran pest Leptinotarsa decemlineata and to induce compensatory responses in this insect. A functional proteomics procedure to capture target Cys proteases in midgut extracts allowed confirmation of distinct binding profiles for the cystatin variants. A shotgun proteomics procedure to monitor whole Cys protease complements revealed protease family specific compensatory responses in the insect, dependent on the variant ingested. Our data confirm the contribution of closely related amino acids to the functional diversity of positively selected plant cystatins in a broader structure/function context imposing physicochemical constraints to primary structure alterations. They also underline the complexity of protease/inhibitor interactions in plant-insect systems, and the challenges still to be met in order to harness the full potential of ectopically expressed protease inhibitors in crop protection. © 2016 Federation of European Biochemical Societies.

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

24 CFR 35.1220 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Tenant-Based Rental Assistance § 35.1220 Ongoing lead-based paint maintenance activities...

‘Obesity’ is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism

PubMed Central

Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

2015-01-01

Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that ‘obesity’ might be an indicator of good health for cetaceans. PMID:26381091

Isolating "Unknown" Bacteria in the Introductory Microbiology Laboratory: A New Selective Medium for Gram-Positives.

ERIC Educational Resources Information Center

McKillip, John L.; Drake, MaryAnne

1999-01-01

Describes the development, preparation, and use of a medium that can select against a wide variety of Gram-negative bacteria while still allowing growth and differentiation of a wide range of Gram-positives. (WRM)

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

PubMed

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

2015-12-01

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

Design and optimization of selective azaindole amide M1 positive allosteric modulators.

PubMed

Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

2016-01-15

Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Positive Psychology in Context: Effects of Expressing Gratitude in Ongoing Relationships Depend on Perceptions of Enactor Responsiveness

PubMed Central

Algoe, Sara B.; Zhaoyang, Ruixue

2016-01-01

Recent correlational evidence implicates gratitude in personal and relational growth, for both members of ongoing relationships. From these observations, it would be tempting to prescribe interpersonal gratitude exercises to improve relationships. In this experiment, couples were randomly assigned to express gratitude over a month, or to a relationally-active control condition. Results showed modest effects of condition on personal and relational well-being. However, those whose partners were perceived as being particularly responsive when expressing gratitude at the initial lab session showed greater well-being across a range of outcomes, whereas this was not so for people in the control condition. Notably, evidence raises concerns about the effectiveness of artificial injections of gratitude when the partner is perceived to be low in responsiveness. Given the importance of close relationships, this work highlights the need for more theory-driven basic research tested in context before assuming what appears to work naturally will also work artificially. PMID:27800009

Positive Psychology in Context: Effects of Expressing Gratitude in Ongoing Relationships Depend on Perceptions of Enactor Responsiveness.

PubMed

Algoe, Sara B; Zhaoyang, Ruixue

2016-01-01

Recent correlational evidence implicates gratitude in personal and relational growth, for both members of ongoing relationships. From these observations, it would be tempting to prescribe interpersonal gratitude exercises to improve relationships. In this experiment, couples were randomly assigned to express gratitude over a month, or to a relationally-active control condition. Results showed modest effects of condition on personal and relational well-being. However, those whose partners were perceived as being particularly responsive when expressing gratitude at the initial lab session showed greater well-being across a range of outcomes, whereas this was not so for people in the control condition. Notably, evidence raises concerns about the effectiveness of artificial injections of gratitude when the partner is perceived to be low in responsiveness. Given the importance of close relationships, this work highlights the need for more theory-driven basic research tested in context before assuming what appears to work naturally will also work artificially.

24 CFR 35.935 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Rehabilitation § 35.935 Ongoing lead-based paint maintenance activities. In the case of a rental... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Ongoing lead-based paint...

24 CFR 35.935 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Rehabilitation § 35.935 Ongoing lead-based paint maintenance activities. In the case of a rental... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Ongoing lead-based paint...

24 CFR 35.935 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Rehabilitation § 35.935 Ongoing lead-based paint maintenance activities. In the case of a rental... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Ongoing lead-based paint...

24 CFR 35.935 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Rehabilitation § 35.935 Ongoing lead-based paint maintenance activities. In the case of a rental... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Ongoing lead-based paint...

24 CFR 35.935 - Ongoing lead-based paint maintenance activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Rehabilitation § 35.935 Ongoing lead-based paint maintenance activities. In the case of a rental... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Ongoing lead-based paint...

Signatures of positive selection in East African Shorthorn Zebu: a genome-wide SNP analysis

USDA-ARS?s Scientific Manuscript database

The small East African Shorthorn Zebu is the main indigenous cattle across East Africa. A recent genome wide SNPs analysis has revealed their ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signature of positive selection in their genome, with the aim...

DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity

PubMed Central

Naughtin, Monica; Haftek-Terreau, Zofia; Xavier, Johan; Meyer, Sam; Silvain, Maud; Jaszczyszyn, Yan; Levy, Nicolas; Miele, Vincent; Benleulmi, Mohamed Salah; Ruff, Marc; Parissi, Vincent; Vaillant, Cédric; Lavigne, Marc

2015-01-01

Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together, these results indicate that HIV-1 IN is a shape-readout DNA binding protein. PMID:26075397

Influence of needle position on lumbar segmental nerve root block selectivity.

PubMed

Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

Sexual differences in telomere selection in the wild.

PubMed

Olsson, Mats; Pauliny, Angela; Wapstra, Erik; Uller, Tobias; Schwartz, Tonia; Miller, Emily; Blomqvist, Donald

2011-05-01

Telomere length is restored primarily through the action of the reverse transcriptase telomerase, which may contribute to a prolonged lifespan in some but not all species and may result in longer telomeres in one sex than the other. To what extent this is an effect of proximate mechanisms (e.g. higher stress in males, higher oestradiol/oestrogen levels in females), or is an evolved adaptation (stronger selection for telomere length in one sex), usually remains unknown. Sand lizard (Lacerta agilis) females have longer telomeres than males and better maintain telomere length through life than males do. We also show that telomere length more strongly contributes to life span and lifetime reproductive success in females than males and that telomere length is under sexually diversifying selection in the wild. Finally, we performed a selection analysis with number of recruited offspring into the adult population as a response variable with telomere length, life span and body size as predictor variables. This showed significant differences in selection pressures between the sexes with strong ongoing selection in females, with these three predictors explaining 63% of the variation in recruitment. Thus, the sexually dimorphic telomere dynamics with longer telomeres in females is a result of past and ongoing selection in sand lizards. Finally, we compared the results from our selection analyses based on Telometric-derived data to the results based on data generated by the software ImageJ. ImageJ resulted in shorter average telomere length, but this difference had virtually no qualitative effect on the patterns of ongoing selection. © 2011 Blackwell Publishing Ltd.

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

PubMed Central

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

2009-01-01

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

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

PubMed Central

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

2014-01-01

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

Positive selection in the SLC11A1 gene in the family Equidae.

PubMed

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

2016-05-01

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

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

PubMed

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

2013-11-01

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

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.

Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs

PubMed Central

Theunert, Christoph; Pugach, Irina; Li, Jing; Nandineni, Madhusudan R.; Gross, Arnd; Scholz, Markus; Stoneking, Mark

2009-01-01

Background Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. Methodology We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level. Conclusions Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature. PMID:19924308

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

PubMed

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

2008-12-03

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

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

PubMed

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

2018-04-01

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

Assessing Ongoing Electronic Resource Purchases: Linking Tools to Synchronize Staff Workflows

ERIC Educational Resources Information Center

Carroll, Jeffrey D.; Major, Colleen; O'Neal, Nada; Tofanelli, John

2012-01-01

Ongoing electronic resource purchases represent a substantial proportion of collections budgets. Recognizing the necessity of systematic ongoing assessment with full selector engagement, Columbia University Libraries appointed an Electronic Resources Assessment Working Group to promote the inclusion of such resources within our current culture of…

New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1.

PubMed

Coleman, Nichole; Brown, Brandon M; Oliván-Viguera, Aida; Singh, Vikrant; Olmstead, Marilyn M; Valero, Marta Sofia; Köhler, Ralf; Wulff, Heike

2014-09-01

Small-conductance (KCa2) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are voltage-independent and share a common calcium/calmodulin-mediated gating mechanism. Existing positive gating modulators like EBIO, NS309, or SKA-31 activate both KCa2 and KCa3.1 channels with similar potency or, as in the case of CyPPA and NS13001, selectively activate KCa2.2 and KCa2.3 channels. We performed a structure-activity relationship (SAR) study with the aim of optimizing the benzothiazole pharmacophore of SKA-31 toward KCa3.1 selectivity. We identified SKA-111 (5-methylnaphtho[1,2-d]thiazol-2-amine), which displays 123-fold selectivity for KCa3.1 (EC50 111 ± 27 nM) over KCa2.3 (EC50 13.7 ± 6.9 μM), and SKA-121 (5-methylnaphtho[2,1-d]oxazol-2-amine), which displays 41-fold selectivity for KCa3.1 (EC50 109 nM ± 14 nM) over KCa2.3 (EC50 4.4 ± 1.6 μM). Both compounds are 200- to 400-fold selective over representative KV (KV1.3, KV2.1, KV3.1, and KV11.1), NaV (NaV1.2, NaV1.4, NaV1.5, and NaV1.7), as well as CaV1.2 channels. SKA-121 is a typical positive-gating modulator and shifts the calcium-concentration response curve of KCa3.1 to the left. In blood pressure telemetry experiments, SKA-121 (100 mg/kg i.p.) significantly lowered mean arterial blood pressure in normotensive and hypertensive wild-type but not in KCa3.1(-/-) mice. SKA-111, which was found in pharmacokinetic experiments to have a much longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure but also drastically reduced heart rate, presumably through cardiac and neuronal KCa2 activation when dosed at 100 mg/kg. In conclusion, with SKA-121, we generated a KCa3.1-specific positive gating modulator suitable for further exploring the therapeutical potential of KCa3.1 activation. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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

The bereavement process of tissue donors' family members: responses of grief, posttraumatic stress, personal growth, and ongoing attachment.

PubMed

Hogan, Nancy; Schmidt, Lee; Coolican, Maggie

2014-09-01

Donated tissues can save lives of critically burned patients and those needing a heart valve replacement. Tissues enhance the lives of a million recipients annually through transplants of corneas, bones, tendons, and vein grafts. Unfortunately, the need for some tissues exceeds their availability. The goal of the quantitative component of this mixed methods study was to identify the grief, posttraumatic stress, personal growth, and ongoing attachment response of tissue donors' family members during a 2-year period. Simultaneous mixed methods design. The sample for this study consisted of 52 tissue donors' family members, mostly widows (83%). Data were collected for 2 years to test changes in grief, posttraumatic stress, panic behavior, personal growth, and ongoing attachment. The bereaved participants experienced significantly fewer grief reactions, less posttraumatic stress, and greater personal growth. There was no significant difference in the ongoing attachment to their deceased loved ones. The results of this study may reinforce the positive meaning that tissue donors' family members can find in tissue donation. Findings also demonstrate that the bereavement process corroborates contemporary bereavement and attachment theories. Health professionals are encouraged to seek donations with less worry that tissue donors' family members will experience adverse outcomes during bereavement.

Targeting the cyclin D–cyclin-dependent kinase (CDK)4/6–retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions

PubMed Central

Spring, Laura; Bardia, Aditya; Modi, Shanu

2017-01-01

Dysregulation of the cyclin D–cyclin-dependent kinase (CDK)4/6–INK4–retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively nonselective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in ER+ breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicate promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II–III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the rationale for targeting cyclin D–CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combinations strategies with CDK 4/6 backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with ER+ breast cancer. PMID:26896604

24 CFR 35.825 - Ongoing lead-based paint maintenance and reevaluation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES HUD-Owned and Mortgagee-in-Possession Multifamily Property § 35.825 Ongoing lead-based paint...

24 CFR 35.825 - Ongoing lead-based paint maintenance and reevaluation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES HUD-Owned and Mortgagee-in-Possession Multifamily Property § 35.825 Ongoing lead-based paint...

24 CFR 35.825 - Ongoing lead-based paint maintenance and reevaluation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES HUD-Owned and Mortgagee-in-Possession Multifamily Property § 35.825 Ongoing lead-based paint...

24 CFR 35.825 - Ongoing lead-based paint maintenance and reevaluation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES HUD-Owned and Mortgagee-in-Possession Multifamily Property § 35.825 Ongoing lead-based paint...

24 CFR 35.825 - Ongoing lead-based paint maintenance and reevaluation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Ongoing lead-based paint..., Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES HUD-Owned and Mortgagee-in-Possession Multifamily Property § 35.825 Ongoing lead-based paint...

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

PubMed

Middelveen, Marianne J; Sapi, Eva; Burke, Jennie; Filush, Katherine R; Franco, Agustin; Fesler, Melissa C; Stricker, Raphael B

2018-04-14

Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi , in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

Leaks in the pipeline: separating demographic inertia from ongoing gender differences in academia

PubMed Central

Shaw, Allison K.; Stanton, Daniel E.

2012-01-01

Identification of the causes underlying the under-representation of women and minorities in academia is a source of ongoing concern and controversy. This is a critical issue in ensuring the openness and diversity of academia; yet differences in personal experiences and interpretations have mired it in controversy. We construct a simple model of the academic career that can be used to identify general trends, and separate the demographic effects of historical differences from ongoing biological or cultural gender differences. We apply the model to data on academics collected by the National Science Foundation (USA) over the past three decades, across all of science and engineering, and within six disciplines (agricultural and biological sciences, engineering, mathematics and computer sciences, physical sciences, psychology, and social sciences). We show that the hiring and retention of women in academia have been affected by both demographic inertia and gender differences, but that the relative influence of gender differences appears to be dwindling for most disciplines and career transitions. Our model enables us to identify the two key non-structural bottlenecks restricting female participation in academia: choice of undergraduate major and application to faculty positions. These transitions are those in greatest need of detailed study and policy development. PMID:22719028

Leaks in the pipeline: separating demographic inertia from ongoing gender differences in academia.

PubMed

Shaw, Allison K; Stanton, Daniel E

2012-09-22

Identification of the causes underlying the under-representation of women and minorities in academia is a source of ongoing concern and controversy. This is a critical issue in ensuring the openness and diversity of academia; yet differences in personal experiences and interpretations have mired it in controversy. We construct a simple model of the academic career that can be used to identify general trends, and separate the demographic effects of historical differences from ongoing biological or cultural gender differences. We apply the model to data on academics collected by the National Science Foundation (USA) over the past three decades, across all of science and engineering, and within six disciplines (agricultural and biological sciences, engineering, mathematics and computer sciences, physical sciences, psychology, and social sciences). We show that the hiring and retention of women in academia have been affected by both demographic inertia and gender differences, but that the relative influence of gender differences appears to be dwindling for most disciplines and career transitions. Our model enables us to identify the two key non-structural bottlenecks restricting female participation in academia: choice of undergraduate major and application to faculty positions. These transitions are those in greatest need of detailed study and policy development.

Stuck on semantics: Processing of irrelevant object-scene inconsistencies modulates ongoing gaze behavior.

PubMed

Cornelissen, Tim H W; Võ, Melissa L-H

2017-01-01

People have an amazing ability to identify objects and scenes with only a glimpse. How automatic is this scene and object identification? Are scene and object semantics-let alone their semantic congruity-processed to a degree that modulates ongoing gaze behavior even if they are irrelevant to the task at hand? Objects that do not fit the semantics of the scene (e.g., a toothbrush in an office) are typically fixated longer and more often than objects that are congruent with the scene context. In this study, we overlaid a letter T onto photographs of indoor scenes and instructed participants to search for it. Some of these background images contained scene-incongruent objects. Despite their lack of relevance to the search, we found that participants spent more time in total looking at semantically incongruent compared to congruent objects in the same position of the scene. Subsequent tests of explicit and implicit memory showed that participants did not remember many of the inconsistent objects and no more of the consistent objects. We argue that when we view natural environments, scene and object relationships are processed obligatorily, such that irrelevant semantic mismatches between scene and object identity can modulate ongoing eye-movement behavior.

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

PubMed Central

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

2016-01-01

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

On Widening Participation in Higher Education through Positive Discrimination

ERIC Educational Resources Information Center

Clayton, Matthew

2012-01-01

Notwithstanding an ongoing concern about the low representation of certain groups in higher education, there is reluctance on the part of politicians and policy makers to adopt positive discrimination as an appropriate means of widening participation. This article offers an account of the different objections to positive discrimination and,…

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.

Time course of ongoing activity during neuritis and following axonal transport disruption.

PubMed

Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

2018-05-01

Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (<10%) A- and C-fiber neurons showed ongoing activity 1-15 days following vinblastine treatment. In contrast, AMS increased transiently at the vinblastine treatment site, peaking on days 4-5 (28% of C/slow Aδ-fiber neurons) and resolved by day 15. Conduction velocities were slowed in all groups. In summary, the disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data

Surfing with spirochaetes: an ongoing syphilis outbreak in Brighton.

PubMed

Poulton, M; Dean, G L; Williams, D I; Carter, P; Iversen, A; Fisher, M

2001-10-01

There has been a recent shift in the epidemiology of early syphilis in the developed world with sporadic outbreaks on a historic low level of background disease. Here we describe an ongoing outbreak of syphilis in Brighton. Data collected on all patients with a diagnosis of early infectious syphilis at Brighton GUM clinic. 30 cases of early syphilis were diagnosed over a 25 month period beginning in July 1999. 28 were homosexual or bisexual men, giving a rate of 134 cases per 100 000 homosexual men. The cases reported a median of three sexual contacts (range 1-50) in the preceding 6 months and 77% had concurrent regular and casual partners. 83% of contacts were casual and untraceable. Over one third (11) of these cases reported oral sex as their only risk factor for syphilis acquisition and were unaware of this transmission route. 70% were diagnosed with primary or secondary infection, the remaining 30% being asymptomatic with early latent infection. Eight of the cases were HIV positive and a further eight remain untested for HIV. At least one concurrent STI was found in 40% of cases. Regular outbreak control meetings, involving relevant healthcare professionals, were held to plan appropriate interventions. The high rate of casual and untraceable contacts in this outbreak suggest that alternative control measures are necessary, including on-site testing and further health education regarding the oral transmission of syphilis. Continued vigilance for syphilis is essential, especially in those patients who are HIV positive.

Conflict, camps and coercion: the ongoing livelihoods crisis in Darfur.

PubMed

Buchanan-Smith, Margie; Jaspars, Susanne

2007-03-01

This paper presents the findings of a study commissioned by World Food Programme (WFP) in early 2006 to enhance understanding of how the conflict in Darfur has affected livelihoods and markets, and of the effects of food aid. The livelihoods of many in Darfur were devastated early on in the conflict, principally through the widespread looting or destruction of assets and highly restricted population movements, which struck at the heart of pre-conflict livelihoods. Livelihood strategies for most people are now restricted, poorly remunerated and often associated with high risk of attack. Patterns of coercion and exploitation have also become entrenched; and markets and trade, the lifeblood of Da fur's economy pre-conflict, severely disrupted. Against this backdrop the impact of food aid on livelihoods in Darfur has been overwhelmingly positive. The paper proposes a number of preconditions for investment in recovery in Darfur, and recommends ways in which livelihoods can be supported in the current context of ongoing conflict.

Pulsed Out of Awareness: EEG Alpha Oscillations Represent a Pulsed-Inhibition of Ongoing Cortical Processing

PubMed Central

Mathewson, Kyle E.; Lleras, Alejandro; Beck, Diane M.; Fabiani, Monica; Ro, Tony; Gratton, Gabriele

2011-01-01

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and we propose that alpha exerts its inhibitory role through alternating microstates of inhibition and excitation. Finally, we discuss evidence that this pulsed-inhibition can be entrained to rhythmic stimuli in the environment, such that preferential processing occurs for stimuli at predictable moments. The entrainment of preferential phase may provide a mechanism for temporal attention in the brain. This pulsed inhibitory account of alpha has important implications for many common cognitive phenomena, such as the attentional blink, and seems to indicate that our visual experience may at least some times be coming through in waves. PMID:21779257

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.

Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

PubMed

Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

2005-01-01

The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

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

PubMed

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

2007-07-01

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

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.

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

The dynamic sustainability framework: addressing the paradox of sustainment amid ongoing change.

PubMed

Chambers, David A; Glasgow, Russell E; Stange, Kurt C

2013-10-02

Despite growth in implementation research, limited scientific attention has focused on understanding and improving sustainability of health interventions. Models of sustainability have been evolving to reflect challenges in the fit between intervention and context. We examine the development of concepts of sustainability, and respond to two frequent assumptions -'voltage drop,' whereby interventions are expected to yield lower benefits as they move from efficacy to effectiveness to implementation and sustainability, and 'program drift,' whereby deviation from manualized protocols is assumed to decrease benefit. We posit that these assumptions limit opportunities to improve care, and instead argue for understanding the changing context of healthcare to continuously refine and improve interventions as they are sustained. Sustainability has evolved from being considered as the endgame of a translational research process to a suggested 'adaptation phase' that integrates and institutionalizes interventions within local organizational and cultural contexts. These recent approaches locate sustainability in the implementation phase of knowledge transfer, but still do not address intervention improvement as a central theme. We propose a Dynamic Sustainability Framework that involves: continued learning and problem solving, ongoing adaptation of interventions with a primary focus on fit between interventions and multi-level contexts, and expectations for ongoing improvement as opposed to diminishing outcomes over time. A Dynamic Sustainability Framework provides a foundation for research, policy and practice that supports development and testing of falsifiable hypotheses and continued learning to advance the implementation, transportability and impact of health services research.

Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons.

PubMed

Holtyn, August F; Kaminski, Barbara J; Weerts, Elise M

2017-10-01

Baclofen, a GABA B receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8mg/kg) or naltrexone (1.0-5.6mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8mg/kg) and naltrexone (3.2 and 5.6mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6mg/kg), but not baclofen, significantly reduced alcohol seeking. Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2009-01-01

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

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

PubMed Central

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

2009-01-01

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

Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria.

PubMed

Boivin, Michael J; Gladstone, Melissa J; Vokhiwa, Maclean; Birbeck, Gretchen L; Magen, Jed G; Page, Connie; Semrud-Clikeman, Margaret; Kauye, Felix; Taylor, Terrie E

2011-03-01

To assess children with retinopathy-positive cerebral malaria (CM) for neurocognitive sequelae. Participants were selected from an ongoing exposure-control study. Eighty-three Malawian children averaging 4.4 years of age and diagnosed with retinopathy-positive CM were compared to 95 controls. Each child was classified as delayed or not using age-based norms for the Malawi Developmental Assessment Tool (MDAT) for developmental delay on the total scale and for the domains of gross motor, fine motor, language and social skills. Groups were also compared on the Achenbach Child Behaviour Checklist (CBCL) (1.5-5 years). Children with retinopathy-positive CM were delayed, relative to the comparison group, on MDAT total development (P = 0.028; odds ratio or OR = 2.13), with the greatest effects on language development (P = 0.003; OR = 4.93). The two groups did not differ significantly on the Achenbach CBCL internalizing and externalizing symptoms total scores. Stepwise regression demonstrated that coma duration, seizures while in hospital, platelet count and lactate level on admission were predictive of assessment outcomes for the children with retinopathy-positive CM. Children who suffer retinopathy-positive CM at preschool age are at greater risk of developmental delay, particularly with respect to language development. This confirms previous retrospective study findings with school-age children evaluated years after acute illness. The MDAT and the Achenbach CBCL proved sensitive to clinical indicators of severity of malarial illness. © 2010 Blackwell Publishing Ltd.

EMERGING CONTAMINANTS: AN OVERVIEW OF ON-GOING RESEARCH

EPA Science Inventory

This presentation covers an overview of research on emerging contaminants on-going at

U.S. EPA's National Exposure Research Laboratory in Las Vegas. Due to the

improvements and sophistication of recent analytical instruments, increasing numbers of

chemicals a...

The dynamic sustainability framework: addressing the paradox of sustainment amid ongoing change

PubMed Central

2013-01-01

Background Despite growth in implementation research, limited scientific attention has focused on understanding and improving sustainability of health interventions. Models of sustainability have been evolving to reflect challenges in the fit between intervention and context. Discussion We examine the development of concepts of sustainability, and respond to two frequent assumptions —'voltage drop,’ whereby interventions are expected to yield lower benefits as they move from efficacy to effectiveness to implementation and sustainability, and 'program drift,’ whereby deviation from manualized protocols is assumed to decrease benefit. We posit that these assumptions limit opportunities to improve care, and instead argue for understanding the changing context of healthcare to continuously refine and improve interventions as they are sustained. Sustainability has evolved from being considered as the endgame of a translational research process to a suggested 'adaptation phase’ that integrates and institutionalizes interventions within local organizational and cultural contexts. These recent approaches locate sustainability in the implementation phase of knowledge transfer, but still do not address intervention improvement as a central theme. We propose a Dynamic Sustainability Framework that involves: continued learning and problem solving, ongoing adaptation of interventions with a primary focus on fit between interventions and multi-level contexts, and expectations for ongoing improvement as opposed to diminishing outcomes over time. Summary A Dynamic Sustainability Framework provides a foundation for research, policy and practice that supports development and testing of falsifiable hypotheses and continued learning to advance the implementation, transportability and impact of health services research. PMID:24088228

Sequence divergence and diversity suggests ongoing functional diversification of vertebrate NAD metabolism

PubMed Central

Gossmann, Toni I.; Ziegler, Mathias

2014-01-01

NAD is not only an important cofactor in redox reactions but has also received attention in recent years because of its physiological importance in metabolic regulation, DNA repair and signaling. In contrast to the redox reactions, these regulatory processes involve degradation of NAD and therefore necessitate a constant replenishment of its cellular pool. NAD biosynthetic enzymes are common to almost all species in all clades, but the number of NAD degrading enzymes varies substantially across taxa. In particular, vertebrates, including humans, have a manifold of NAD degrading enzymes which require a high turnover of NAD. As there is currently a lack of a systematic study of how natural selection has shaped enzymes involved in NAD metabolism we conducted a comprehensive evolutionary analysis based on intraspecific variation and interspecific divergence. We compare NAD biosynthetic and degrading enzymes in four eukaryotic model species and subsequently focus on human NAD metabolic enzymes and their orthologs in other vertebrates. We find that the majority of enzymes involved in NAD metabolism are subject to varying levels of purifying selection. While NAD biosynthetic enzymes appear to experience a rather high level of evolutionary constraint, there is evidence for positive selection among enzymes mediating NAD-dependent signaling. This is particularly evident for members of the PARP family, a diverse protein family involved in DNA damage repair and programmed cell death. Based on haplotype information and substitution rate analysis we pinpoint sites that are potential targets of positive selection. We also link our findings to a three dimensional structure, which suggests that positive selection occurs in domains responsible for DNA binding and polymerization rather than the NAD catalytic domain. Taken together, our results indicate that vertebrate NAD metabolism is still undergoing functional diversification. PMID:25084685

Sequence divergence and diversity suggests ongoing functional diversification of vertebrate NAD metabolism.

PubMed

Gossmann, Toni I; Ziegler, Mathias

2014-11-01

NAD is not only an important cofactor in redox reactions but has also received attention in recent years because of its physiological importance in metabolic regulation, DNA repair and signaling. In contrast to the redox reactions, these regulatory processes involve degradation of NAD and therefore necessitate a constant replenishment of its cellular pool. NAD biosynthetic enzymes are common to almost all species in all clades, but the number of NAD degrading enzymes varies substantially across taxa. In particular, vertebrates, including humans, have a manifold of NAD degrading enzymes which require a high turnover of NAD. As there is currently a lack of a systematic study of how natural selection has shaped enzymes involved in NAD metabolism we conducted a comprehensive evolutionary analysis based on intraspecific variation and interspecific divergence. We compare NAD biosynthetic and degrading enzymes in four eukaryotic model species and subsequently focus on human NAD metabolic enzymes and their orthologs in other vertebrates. We find that the majority of enzymes involved in NAD metabolism are subject to varying levels of purifying selection. While NAD biosynthetic enzymes appear to experience a rather high level of evolutionary constraint, there is evidence for positive selection among enzymes mediating NAD-dependent signaling. This is particularly evident for members of the PARP family, a diverse protein family involved in DNA damage repair and programmed cell death. Based on haplotype information and substitution rate analysis we pinpoint sites that are potential targets of positive selection. We also link our findings to a three dimensional structure, which suggests that positive selection occurs in domains responsible for DNA binding and polymerization rather than the NAD catalytic domain. Taken together, our results indicate that vertebrate NAD metabolism is still undergoing functional diversification. Crown Copyright © 2014. Published by Elsevier B

Eye-movements and ongoing task processing.

PubMed

Burke, David T; Meleger, Alec; Schneider, Jeffrey C; Snyder, Jim; Dorvlo, Atsu S S; Al-Adawi, Samir

2003-06-01

This study tests the relation between eye-movements and thought processing. Subjects were given specific modality tasks (visual, gustatory, kinesthetic) and assessed on whether they responded with distinct eye-movements. Some subjects' eye-movements reflected ongoing thought processing. Instead of a universal pattern, as suggested by the neurolinguistic programming hypothesis, this study yielded subject-specific idiosyncratic eye-movements across all modalities. Included is a discussion of the neurolinguistic programming hypothesis regarding eye-movements and its implications for the eye-movement desensitization and reprocessing theory.

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

Genes under positive selection in a model plant pathogenic fungus, Botrytis.

PubMed

Aguileta, Gabriela; Lengelle, Juliette; Chiapello, Hélène; Giraud, Tatiana; Viaud, Muriel; Fournier, Elisabeth; Rodolphe, François; Marthey, Sylvain; Ducasse, Aurélie; Gendrault, Annie; Poulain, Julie; Wincker, Patrick; Gout, Lilian

2012-07-01

The rapid evolution of particular genes is essential for the adaptation of pathogens to new hosts and new environments. Powerful methods have been developed for detecting targets of selection in the genome. Here we used divergence data to compare genes among four closely related fungal pathogens adapted to different hosts to elucidate the functions putatively involved in adaptive processes. For this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant species. A maximum likelihood-based analysis of 642 predicted orthologs detected 21 genes showing footprints of positive selection. These results were validated by resequencing nine of these genes in additional Botrytis species, showing they have also been rapidly evolving in other related species. Twenty of the 21 genes had not previously been identified as pathogenicity factors in B. cinerea, but some had functions related to plant-fungus interactions. The putative functions were involved in respiratory and energy metabolism, protein and RNA metabolism, signal transduction or virulence, similarly to what was detected in previous studies using the same approach in other pathogens. Mutants of B. cinerea were generated for four of these genes as a first attempt to elucidate their functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Multi-scale textural feature extraction and particle swarm optimization based model selection for false positive reduction in mammography.

PubMed

Zyout, Imad; Czajkowska, Joanna; Grzegorzek, Marcin

2015-12-01

The high number of false positives and the resulting number of avoidable breast biopsies are the major problems faced by current mammography Computer Aided Detection (CAD) systems. False positive reduction is not only a requirement for mass but also for calcification CAD systems which are currently deployed for clinical use. This paper tackles two problems related to reducing the number of false positives in the detection of all lesions and masses, respectively. Firstly, textural patterns of breast tissue have been analyzed using several multi-scale textural descriptors based on wavelet and gray level co-occurrence matrix. The second problem addressed in this paper is the parameter selection and performance optimization. For this, we adopt a model selection procedure based on Particle Swarm Optimization (PSO) for selecting the most discriminative textural features and for strengthening the generalization capacity of the supervised learning stage based on a Support Vector Machine (SVM) classifier. For evaluating the proposed methods, two sets of suspicious mammogram regions have been used. The first one, obtained from Digital Database for Screening Mammography (DDSM), contains 1494 regions (1000 normal and 494 abnormal samples). The second set of suspicious regions was obtained from database of Mammographic Image Analysis Society (mini-MIAS) and contains 315 (207 normal and 108 abnormal) samples. Results from both datasets demonstrate the efficiency of using PSO based model selection for optimizing both classifier hyper-parameters and parameters, respectively. Furthermore, the obtained results indicate the promising performance of the proposed textural features and more specifically, those based on co-occurrence matrix of wavelet image representation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-08-01

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

42 CFR 460.192 - Ongoing monitoring after trial period.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Federal/State Monitoring § 460.192 Ongoing monitoring after trial period. (a...

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

PubMed Central

2011-01-01

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

Molecular adaptation in Rubisco: Discriminating between convergent evolution and positive selection using mechanistic and classical codon models.

PubMed

Parto, Sahar; Lartillot, Nicolas

2018-01-01

Rubisco (Ribulose-1, 5-biphosphate carboxylase/oxygenase) is the most important enzyme on earth, catalyzing the first step of photosynthetic CO2 fixation. So, without it, there would be no storing of the sun's energy in plants. Molecular adaptation of Rubisco to C4 photosynthetic pathway has attracted a lot of attention. C4 plants, which comprise less than 5% of land plants, have evolved more efficient photosynthesis compared to C3 plants. Interestingly, a large number of independent transitions from C3 to C4 phenotype have occurred. Each time, the Rubisco enzyme has been subject to similar changes in selective pressure, thus providing an excellent model for convergent evolution at the molecular level. Molecular adaptation is often identified with positive selection and is typically characterized by an elevated ratio of non-synonymous to synonymous substitution rate (dN/dS). However, convergent adaptation is expected to leave a different molecular signature, taking the form of repeated transitions toward identical or similar amino acids. Here, we used a previously introduced codon-based differential-selection model to detect and quantify consistent patterns of convergent adaptation in Rubisco in eudicots. We further contrasted our results with those obtained by classical codon models based on the estimation of dN/dS. We found that the two classes of models tend to select distinct, although overlapping, sets of positions. This discrepancy in the results illustrates the conceptual difference between these models while emphasizing the need to better discriminate between qualitatively different selective regimes, by using a broader class of codon models than those currently considered in molecular evolutionary studies.

A Response to Frederick Hess: An Ongoing Conversation

ERIC Educational Resources Information Center

Bacchetti, Ray

2004-01-01

In this article, the author comments on the article "An Ongoing Conversation", by Frederick Hess. The author points out that the increasing polarization of the public's views on public education serves us poorly and we need to revive the skill and will to engage in more thoughtful dialogue.

Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain.

PubMed

Lew, S; Hämäläinen, M S; Okada, Y

2017-12-01

To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs. A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure. The magnetic fields from internal organs and an external noise source were computed for a pregnant woman with a 35-week old fetus. Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain. External interference was reduced by a factor of 1000, sufficient for detecting signals from internal organs when combined with passive and active shielding. The scanner rejects internal interferences better than partial-coverage arrays. It can be used to estimate currents around the uterus. It clearly detects spontaneous activity from the fetal heart and brain without averaging and weaker evoked brain activity at all fetal head positions after averaging. The simulated device will be able to monitor the ongoing activity of the fetal and maternal organs. This type of scanner may become a novel tool in fetal medicine. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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

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.

Characterizing Age-Related Positivity Effects in Situation Selection

ERIC Educational Resources Information Center

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

2018-01-01

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

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)

Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology.

PubMed

Moon, Jiyun M; Aronoff, David M; Capra, John A; Abbot, Patrick; Rokas, Antonis

2018-03-28

Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that

Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry

PubMed Central

2013-01-01

Background Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima’s D, Fay and Wu’s H and Fu and Li’s D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Results Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. Conclusions We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a

Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry.

PubMed

Hider, Jessica L; Gittelman, Rachel M; Shah, Tapan; Edwards, Melissa; Rosenbloom, Arnold; Akey, Joshua M; Parra, Esteban J

2013-07-12

Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will

An ongoing multifamily group in a women's shelter.

PubMed

Rhodes, Rosetta M; Zelman, Arthur B

1986-01-01

A mental health clinic's consultation to a spouse abuse center led to formation of an ongoing multifamily group that included all residents of the shelter and their children of all ages. The theoretical framework is outlined and group dynamics are highlighted by case material focused on illustrating specific intervention techniques.

Ongoing exposure versus intense periodic exposure to military conflict and terror attacks in Israel.

PubMed

Lahad, Mooli; Leykin, Dmitry

2010-12-01

The manifestation of posttraumatic stress disorder (PTSD) symptoms in two clinical samples in Israel (N = 212) was examined. Individuals suffering ongoing exposure to shelling were compared with subjects exposed to intense periodic exposure. Elevated arousal and avoidance symptoms, but not intrusion were reported in the ongoing exposure group. When compared by age, young participants in the ongoing exposure group had significantly lower PTSD scores, whereas no differences were found between participants among the intense periodic exposure age groups. No gender differences in symptoms were found among participants from intense periodic exposure, whereas in the other ongoing group the difference was in avoidance. Results are discussed in light of past research on exposure to terrorism. Copyright © 2010 International Society for Traumatic Stress Studies.

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

PubMed Central

Stasche, Norbert

2006-01-01

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

Successful ongoing pregnancies after vitrification of oocytes.

PubMed

Lucena, Elkin; Bernal, Diana Patricia; Lucena, Carolina; Rojas, Alejandro; Moran, Abby; Lucena, Andrés

2006-01-01

To demonstrate the efficiency of vitrifying mature human oocytes for different clinical indications. Descriptive case series. Cryobiology laboratory, Centro Colombiano de Fertilidad y Esterilidad-CECOLFES LTDA. (Bogotá, Colombia). Oocyte vitrification was offered as an alternative management for patients undergoing infertility treatment because of ovarian hyperstimulation syndrome, premature ovarian failure, natural ovarian failure, male factor, poor response, or oocyte donation. Mature oocytes were obtained from 33 donor women and 40 patients undergoing infertility treatment. Oocytes were retrieved by ultrasound-guided transvaginal aspiration and vitrified with the Cryotops method, with 30% ethylene glycol, 30% dimethyl sulfoxide, and 0.5 mol/L sucrose. Viability was assessed 3 hours after thawing. The surviving oocytes were inseminated by intracytoplasmic sperm injection. Fertilization was evaluated after 24 hours. The zygotes were further cultured in vitro for up to 72 hours until time of embryo transfer. Recovery, viability, fertilization, and pregnancy rates. Oocyte vitrification with the Cryotop method resulted in high rates of recovery, viability, fertilization, cleavage, and ongoing pregnancy. Vitrification with the Cryotop method is an efficient, fast, and economical method for oocyte cryopreservation that offers high rates of survival, fertilization, embryo development, and ongoing normal pregnancies, providing a new alternative for the management of female infertility.

Position statement on cannabis.

PubMed

Stein, Dan Joseph

2016-05-16

There is an ongoing national debate around cannabis policy. This brief position statement by the Executive Committee of the Central Drug Authorityoutlines some of the factors that have contributed to this debate, delineates reduction strategies, summarises the harms and benefits ofmarijuana, and provides recommendations. These recommendations emphasise an integrated and evidence-based approach, the need forresources to implement harm reduction strategies against continued and chronic use of alcohol and cannabis, and the potential value of afocus on decriminalisation rather than the legalisation of cannabis.

Ongoing change of site conditions important for sustainable forest management planning

NASA Astrophysics Data System (ADS)

Bidló, András; Horváth, Adrienn; Gulyás, Krisztina; Gálos, Borbála

2016-04-01

Observed tree mortality of the last decades has shown that the vulnerable forest ecosystems are especially affected by the recurrent, long lasting droughts, heat waves and their consequences. From all site conditions climate is changing the fastest, in this way it can be the largest threatening factor in the 21st century. Beyond climate, soil characteristics are playing an important influencing role. Until now, silvicultural technologies and species preferences of many countries are prescribed by binding regulation based on climate conditions that are assumed to be constant over time. Therefore the aim of our research was to investigate the ongoing and projected change of site conditions that are considered to be of primary importance in terms of tree species selection. For a case study region in Hungary (Keszthely Mountains, near to Lake Balaton) long-term climate tendencies have been determined for the period 1961-2100, as well as a detailed soil sample analysis has been carried out including ~100 sites. Results show a 0.5 degree increase of temperature and a 6-7 % decrease of the precipitation amount for the summer months in the last decades. For the future, significant warming and drying of summers is expected. Decrease of the summer precipitation sum can exceed 25 % until the end of the century, probability of extreme hot days may increase. These tendencies together with the unfavourable soil conditions and biotic damages can be the reason of the ongoing forest dieback. One of the characteristic soil type of the region is rendzina with a thin topsoil layer and an unfavourable water holding capacity. These properties are limiting the amount of available water for plants, especially in case of intense precipitation events. Black pine stands planted on rendzinas after many years of grazing; therefore erosion may have played a significant role. Not only microclimate conditions but also soil types show a large diversity within a relatively small distance. However

Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection▿

PubMed Central

Humphreys, Isla; Fleming, Vicki; Fabris, Paolo; Parker, Joe; Schulenberg, Bodo; Brown, Anthony; Demetriou, Charis; Gaudieri, Silvana; Pfafferott, Katja; Lucas, Michaela; Collier, Jane; Huang, Kuan-Hsiang Gary; Pybus, Oliver G.; Klenerman, Paul; Barnes, Eleanor

2009-01-01

Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed. We performed full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a infection and assessed genomic viral variability in comparison to other HCV subtypes. Two novel regions of intragenotypic hypervariability within the envelope protein E2, of HCV genotype 3a, were identified. We named these regions HVR495 and HVR575. They consisted of flanking conserved hydrophobic amino acids and central variable residues. A 5-amino-acid insertion found only in genotype 3a and a putative glycosylation site is contained within HVR575. Evolutionary analysis of E2 showed that positively selected sites within genotype 3a infection were largely restricted to HVR1, HVR495, and HVR575. Further analysis of clonal viral populations within single hosts showed that viral variation within HVR495 and HVR575 were subject to intrahost positive selecting forces. Longitudinal analysis of four patients with acute HCV subtype 3a infection sampled at multiple time points showed that positively selected mutations within HVR495 and HVR575 arose early during primary infection. HVR495 and HVR575 were not present in HCV subtypes 1a, 1b, 2a, or 6a. Some variability that was not subject to positive selection was present in subtype 4a HVR575. Further defining the functional significance of these regions may have important implications for genotype 3a E2 virus-receptor interactions and for vaccine studies that aim to induce cross-reactive anti-E2 antibodies. PMID:19740991

SU-G-BRC-13: Model Based Classification for Optimal Position Selection for Left-Sided Breast Radiotherapy: Free Breathing, DIBH, Or Prone

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

Lin, H; Liu, T; Xu, X

Purpose: There are clinical decision challenges to select optimal treatment positions for left-sided breast cancer patients—supine free breathing (FB), supine Deep Inspiration Breath Hold (DIBH) and prone free breathing (prone). Physicians often make the decision based on experiences and trials, which might not always result optimal OAR doses. We herein propose a mathematical model to predict the lowest OAR doses among these three positions, providing a quantitative tool for corresponding clinical decision. Methods: Patients were scanned in FB, DIBH, and prone positions under an IRB approved protocol. Tangential beam plans were generated for each position, and OAR doses were calculated.more » The position with least OAR doses is defined as the optimal position. The following features were extracted from each scan to build the model: heart, ipsilateral lung, breast volume, in-field heart, ipsilateral lung volume, distance between heart and target, laterality of heart, and dose to heart and ipsilateral lung. Principal Components Analysis (PCA) was applied to remove the co-linearity of the input data and also to lower the data dimensionality. Feature selection, another method to reduce dimensionality, was applied as a comparison. Support Vector Machine (SVM) was then used for classification. Thirtyseven patient data were acquired; up to now, five patient plans were available. K-fold cross validation was used to validate the accuracy of the classifier model with small training size. Results: The classification results and K-fold cross validation demonstrated the model is capable of predicting the optimal position for patients. The accuracy of K-fold cross validations has reached 80%. Compared to PCA, feature selection allows causal features of dose to be determined. This provides more clinical insights. Conclusion: The proposed classification system appeared to be feasible. We are generating plans for the rest of the 37 patient images, and more statistically

Internal Capabilities, External Network Position, and Knowledge Creation

ERIC Educational Resources Information Center

Liao, Yin-Chi

2010-01-01

Despite the general consensus on the importance of interfirm networks, there is an ongoing debate centering on which type of network structure is most beneficial to firm performance. While spanning structural holes--a network position with disconnected partners--is argued to be advantageous in terms of providing access to diverse knowledge,…

Human embryonic curvature studied with 3D ultrasound in ongoing pregnancies and miscarriages.

PubMed

Bogers, Hein; van Uitert, Evelyne M; van Ginkel, Sharon; van der Mooren, Elisabeth D H; Groenenberg, Irene A L; Eilers, Paul H C; Exalto, Niek; Steegers, Eric A P; Steegers-Theunissen, Régine P M

2018-05-01

Embryonic growth is often impaired in miscarriages. It is postulated that derangements in embryonic growth result in abnormalities of the embryonic curvature. This study aims to create first trimester reference charts of the human embryonic curvature and investigate differences between ongoing pregnancies and miscarriages. Weekly ultrasonographic scans from ongoing pregnancies and miscarriages were used from the Rotterdam periconceptional cohort and a cohort of recurrent miscarriages. In 202 ongoing pregnancies and 33 miscarriages, first trimester crown rump length and total arch length were measured to assess the embryonic curvature. The results show that the total arch length increases and shows more variation with advanced gestation. The crown rump length/total arch length ratio shows a strong increase from 8 +0 to 10 +0 weeks and flattening thereafter. No significant difference was observed between the curvature of embryos of ongoing pregnancies and miscarriages. The majority of miscarried embryos could not be measured. Therefore, this technique is too limited to recommend the measurement of the embryonic curvature in clinical practice. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Positive Selection Drives the Evolution of rhino, a Member of the Heterochromatin Protein 1 Family in Drosophila

PubMed Central

Vermaak, Danielle; Henikoff, Steven; Malik, Harmit S

2005-01-01

Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1), which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of “junk DNA” in eukaryotic genomes. PMID:16103923

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

PubMed

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

PubMed Central

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H.; Porreca, Frank

2017-01-01

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients. PMID:28832395

Multilevel Selection Theory and the Evolutionary Functions of Transposable Elements

PubMed Central

Brunet, Tyler D.P.; Doolittle, W. Ford

2015-01-01

One of several issues at play in the renewed debate over “junk DNA” is the organizational level at which genomic features might be seen as selected, and thus to exhibit function, as etiologically defined. The intuition frequently expressed by molecular geneticists that junk DNA is functional because it serves to “speed evolution” or as an “evolutionary repository” could be recast as a claim about selection between species (or clades) rather than within them, but this is not often done. Here, we review general arguments for the importance of selection at levels above that of organisms in evolution, and develop them further for a common genomic feature: the carriage of transposable elements (TEs). In many species, not least our own, TEs comprise a large fraction of all nuclear DNA, and whether they individually or collectively contribute to fitness—or are instead junk— is a subject of ongoing contestation. Even if TEs generally owe their origin to selfish selection at the lowest level (that of genomes), their prevalence in extant organisms and the prevalence of extant organisms bearing them must also respond to selection within species (on organismal fitness) and between species (on rates of speciation and extinction). At an even higher level, the persistence of clades may be affected (positively or negatively) by TE carriage. If indeed TEs speed evolution, it is at these higher levels of selection that such a function might best be attributed to them as a class. PMID:26253318

Prospective memory in young and older adults: the effects of task importance and ongoing task load.

PubMed

Smith, Rebekah E; Hunt, R Reed

2014-01-01

Remembering to perform an action in the future, called prospective memory, often shows age-related differences in favor of young adults when tested in the laboratory. Recently Smith, Horn, and Bayen (2012; Aging, Neuropsychology, and Cognition, 19, 495) embedded a PM task in an ongoing color-matching task and manipulated the difficulty of the ongoing task by varying the number of colors on each trial of the task. Smith et al. found that age-related differences in PM performance (lower PM performance for older adults relative to young adults) persisted even when older adults could perform the ongoing task as well or better than the young adults. The current study investigates a possible explanation for the pattern of results reported by Smith et al. by including a manipulation of task emphasis: for half of the participants the prospective memory task was emphasize, while for the other half the ongoing color-matching task was emphasized. Older adults performed a 4-color version of the ongoing color-matching task, while young adults completed either the 4-color or a more difficult 6-color version of the ongoing task. Older adults failed to perform as well as the young adults on the prospective memory task regardless of task emphasis, even when older adults were performing as well or better than the young adults on the ongoing color-matching task. The current results indicate that the lack of an effect of ongoing task load on prospective memory task performance is not due to a perception that one or the other task is more important than the other.

Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians

PubMed Central

Chen, Yuan; Xue, Yali; Luiselli, Donata; Tyler-Smith, Chris; Pagani, Luca; Ayub, Qasim

2015-01-01

Vitamin D and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from Africa into Eurasia. We investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by Phase I of the 1000 Genomes Project. Comparing allele frequency-spectrum-based summary statistics between these gene sets and matched control genes, we observed a selection signal specific to East Asians for a gene set associated with vitamin D action in bones. The selection signal was mainly driven by three genes CXXC finger protein 1 (CXXC1), low density lipoprotein receptor-related protein 5 (LRP5) and runt-related transcription factor 2 (RUNX2). Examination of population differentiation and haplotypes allowed us to identify several candidate causal regulatory variants in each gene. Four of these candidate variants (one each in CXXC1 and RUNX2 and two in LRP5) had a >70% derived allele frequency in East Asians, but were present at lower (20–60%) frequency in Europeans as well, suggesting that the adaptation might have been part of a common response to climatic and dietary changes as humans expanded out of Africa, with implications for their role in vitamin D-dependent bone mineralization and osteoporosis insurgence. We also observed haplotype sharing between East Asians, Finns and an extinct archaic human (Denisovan) sample at the CXXC1 locus, which is best explained by incomplete lineage sorting. PMID:26719974

Feature-selective attention in healthy old age: a selective decline in selective attention?

PubMed

Quigley, Cliodhna; Müller, Matthias M

2014-02-12

Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.

Distinction of Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium salts with a selection medium.

PubMed

Tsukatani, Tadayuki; Suenaga, Hikaru; Higuchi, Tomoko; Shiga, Masanobu; Noguchi, Katsuya; Matsumoto, Kiyoshi

2011-01-01

Bacteria are fundamentally divided into two groups: Gram-positive and Gram-negative. Although the Gram stain and other techniques can be used to differentiate these groups, some issues exist with traditional approaches. In this study, we developed a method for differentiating Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of the tetrazolium salt {2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt} (WST-8) via 2-methyl-1,4-napthoquinone with a selection medium. We optimized the composition of the selection medium to allow the growth of Gram-negative bacteria while inhibiting the growth of Gram-positive bacteria. When the colorimetric viability assay was carried out in a selection medium containing 0.5µg/ml crystal violet, 5.0 µg/ml daptomycin, and 5.0µg/ml vancomycin, the reduction in WST-8 by Gram-positive bacteria was inhibited. On the other hand, Gram-negative bacteria produced WST-8-formazan in the selection medium. The proposed method was also applied to determine the Gram staining characteristics of bacteria isolated from various foodstuffs. There was good agreement between the results obtained using the present method and those obtained using a conventional staining method. These results suggest that the WST-8 colorimetric assay with selection medium is a useful technique for accurately differentiating Gram-positive and -negative bacteria.

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes

PubMed Central

Fry, Andrew E.; Ghansa, Anita; Small, Kerrin S.; Palma, Alejandro; Auburn, Sarah; Diakite, Mahamadou; Green, Angela; Campino, Susana; Teo, Yik Y.; Clark, Taane G.; Jeffreys, Anna E.; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J.; Peshu, Norbert; Williams, Thomas N.; Newton, Charles R.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Koram, Kwadwo A.; Oduro, Abraham R.; Rogers, William O.; Rockett, Kirk A.; Sabeti, Pardis C.; Kwiatkowski, Dominic P.

2009-01-01

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case–control study of 1350 subjects and a family study of 1288 parent–offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10 922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89–1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency. PMID:19403559

Positive selection of a CD36 nonsense variant in sub-Saharan Africa, but no association with severe malaria phenotypes.

PubMed

Fry, Andrew E; Ghansa, Anita; Small, Kerrin S; Palma, Alejandro; Auburn, Sarah; Diakite, Mahamadou; Green, Angela; Campino, Susana; Teo, Yik Y; Clark, Taane G; Jeffreys, Anna E; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Griffiths, Michael J; Peshu, Norbert; Williams, Thomas N; Newton, Charles R; Marsh, Kevin; Molyneux, Malcolm E; Taylor, Terrie E; Koram, Kwadwo A; Oduro, Abraham R; Rogers, William O; Rockett, Kirk A; Sabeti, Pardis C; Kwiatkowski, Dominic P

2009-07-15

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10,922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies

PubMed Central

Briscoe, Adriana D.; Bybee, Seth M.; Bernard, Gary D.; Yuan, Furong; Sison-Mangus, Marilou P.; Reed, Robert D.; Warren, Andrew D.; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

2010-01-01

The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)—a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with λmax = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate. PMID:20133601

Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies.

PubMed

Briscoe, Adriana D; Bybee, Seth M; Bernard, Gary D; Yuan, Furong; Sison-Mangus, Marilou P; Reed, Robert D; Warren, Andrew D; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

2010-02-23

The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)-a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with lambda(max) = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate.

Trauma-Focused CBT for Youth Who Experience Ongoing Traumas

ERIC Educational Resources Information Center

Cohen, Judith A.; Mannarino, Anthony P.; Murray, Laura K.

2011-01-01

Many youth experience ongoing trauma exposure, such as domestic or community violence. Clinicians often ask whether evidence-based treatments containing exposure components to reduce learned fear responses to historical trauma are appropriate for these youth. Essentially the question is, if youth are desensitized to their trauma experiences, will…

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

PubMed

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

2016-09-01

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

THE DEFENSIVE NATURE OF BENEFIT FINDING DURING ONGOING TERRORISM: AN EXAMINATION OF A NATIONAL SAMPLE OF ISRAELI JEWS

PubMed Central

HALL, BRIAN J.; HOBFOLL, STEVAN E.; CANETTI, DAPHNA; JOHNSON, ROBERT J.; GALEA, SANDRO

2011-01-01

A study examining the effects of terrorism on a national sample of 1,136 Jewish adults was conducted in Israel via telephone surveys, during the Second Intifada. The relationship between reports of positive changes occurring subsequent to terrorism exposure (i.e., Benefit finding), posttraumatic stress disorder (PTSD) symptom severity, and negative outgroup attitudes toward Palestinian citizens of Israel (PCI) was examined. Benefit finding was related to greater PTSD symptom severity. Further, Benefit finding was related to greater threat perception of PCI and ethnic exclusionism of PCI. Findings were consistent with hypotheses derived from theories of outgroup bias and support the anxiety buffering role of social affiliation posited by terror management theory. This study suggests that benefit finding may be a defensive coping strategy when expressed under the conditions of ongoing terrorism and external threat. PMID:22058603

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

PubMed

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

2015-06-01

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

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.

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

10 CFR 1045.20 - Ongoing call for declassification proposals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... from the public or agencies or contractors for declassification of RD and FRD information on an ongoing basis. Declassification proposals for RD and FRD information shall be forwarded to the Chief Health... declassification proposals for FRD information. [62 FR 68509, Dec. 31, 1997, as amended at 71 FR 68737, Nov. 28...

10 CFR 1045.20 - Ongoing call for declassification proposals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... from the public or agencies or contractors for declassification of RD and FRD information on an ongoing basis. Declassification proposals for RD and FRD information shall be forwarded to the Chief Health... declassification proposals for FRD information. [62 FR 68509, Dec. 31, 1997, as amended at 71 FR 68737, Nov. 28...

10 CFR 1045.20 - Ongoing call for declassification proposals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... from the public or agencies or contractors for declassification of RD and FRD information on an ongoing basis. Declassification proposals for RD and FRD information shall be forwarded to the Chief Health... declassification proposals for FRD information. [62 FR 68509, Dec. 31, 1997, as amended at 71 FR 68737, Nov. 28...

10 CFR 1045.20 - Ongoing call for declassification proposals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... from the public or agencies or contractors for declassification of RD and FRD information on an ongoing basis. Declassification proposals for RD and FRD information shall be forwarded to the Chief Health... declassification proposals for FRD information. [62 FR 68509, Dec. 31, 1997, as amended at 71 FR 68737, Nov. 28...

10 CFR 1045.20 - Ongoing call for declassification proposals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... from the public or agencies or contractors for declassification of RD and FRD information on an ongoing basis. Declassification proposals for RD and FRD information shall be forwarded to the Chief Health... declassification proposals for FRD information. [62 FR 68509, Dec. 31, 1997, as amended at 71 FR 68737, Nov. 28...

Improved tank car design development : ongoing studies on sandwich structures

DOT National Transportation Integrated Search

2009-03-02

The Government and industry have a common interest in : improving the safety performance of railroad tank cars carrying : hazardous materials. Research is ongoing to develop strategies : to maintain the structural integrity of railroad tank cars carr...

Assessing ongoing sources of dissolved-phase polychlorinated biphenyls in a contaminated stream

USGS Publications Warehouse

Dang, Viet D.; Walters, David M.; Lee, Cindy M.

2013-01-01

Few studies assess the potential of ongoing sources of “fresh” polychlorinated biphenyls (PCBs) to aquatic systems when direct discharge to the environment has been eliminated. In the present study, the authors used single-layered, low-density polyethylene samplers (PEs) to measure total PCB concentrations, congener profiles, and enantiomeric fractions (EFs) in a contaminated stream and to provide multiple lines of evidence for assessing ongoing inputs of PCB. Concentrations were well above background levels that have been monitored for years. Concentrations significantly increased with distance, the farthest downstream PE concentrations being almost five times greater than those at 79 m downstream of a historical point source. The PCBs in the PEs at 79 m downstream of the contamination source were dominated by low KOW congeners, similar to those in the mixture of Aroclors 1016 and 1254 (4:1 v/v) historically released from the former capacitor manufacturer. The only two chiral congeners detected in the PEs downstream were PCBs 91 and 95. The EF values were nonracemic for PCB 91, while the values were either racemic or near racemic for PCB 95. Increased PCB concentrations with distance and a congener composition of predominantly low-weight congeners in the PEs at 79 m downstream of the plant site suggested an ongoing PCB source from the plant site. Chiral signatures suggested aerobic biotransformation of dissolved PCBs but did not shed any light on possible ongoing PCB inputs.

Acquisition of Cleanroom Research Equipment to Support Ongoing DoD Programs at ASU

DTIC Science & Technology

2017-12-12

Report: Acquisition of cleanroom research equipment to support ongoing DoD programs at ASU The views, opinions and/or findings contained in this report...documentation. 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709...Agreement Number: W911NF-16-1-0354 Organization: Arizona State University Title: Acquisition of cleanroom research equipment to support ongoing DoD

Refugee Health: An Ongoing Commitment and Challenge

PubMed Central

Efird, Jimmy T.; Bith-Melander, Pollie

2018-01-01

Refugees represent a diverse group of displaced individuals with unique health issues and disease risks. The obstacles facing this population have their origins in war, violence, oppression, exploitation, and fear of persecution. Regardless of country of origin, a common bond exists, with refugees often confronting inadequate healthcare resources, xenophobia, discrimination, and a complex web of legal barriers in their new homelands. In many cases, the plight of refugees is multigenerational, manifesting as mental health issues, abuse, poverty, and family disruption. The health trajectory of refugees remains an ongoing commitment and challenge. PMID:29342831

Signatures of positive selection in East African Shorthorn Zebu: A genome-wide single nucleotide polymorphism analysis

PubMed Central

Bahbahani, Hussain; Clifford, Harry; Wragg, David; Mbole-Kariuki, Mary N; Van Tassell, Curtis; Sonstegard, Tad; Woolhouse, Mark; Hanotte, Olivier

2015-01-01

The small East African Shorthorn Zebu (EASZ) is the main indigenous cattle across East Africa. A recent genome wide SNP analysis revealed an ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signatures of positive selection in their genome, with the aim to provide qualitative insights about the corresponding selective pressures. Four hundred and twenty-five EASZ and four reference populations (Holstein-Friesian, Jersey, N’Dama and Nellore) were analysed using 46,171 SNPs covering all autosomes and the X chromosome. Following FST and two extended haplotype homozygosity-based (iHS and Rsb) analyses 24 candidate genome regions within 14 autosomes and the X chromosome were revealed, in which 18 and 4 were previously identified in tropical-adapted and commercial breeds, respectively. These regions overlap with 340 bovine QTL. They include 409 annotated genes, in which 37 were considered as candidates. These genes are involved in various biological pathways (e.g. immunity, reproduction, development and heat tolerance). Our results support that different selection pressures (e.g. environmental constraints, human selection, genome admixture constrains) have shaped the genome of EASZ. We argue that these candidate regions represent genome landmarks to be maintained in breeding programs aiming to improve sustainable livestock productivity in the tropics. PMID:26130263

Ongoing child welfare services: Understanding the relationship of worker and organizational characteristics to service provision.

PubMed

Lwin, Kristen; Fluke, John; Trocmé, Nico; Fallon, Barbara; Mishna, Faye

2018-06-01

Ongoing child welfare services are put in place after completion of the initial maltreatment investigation when there is a perceived need to mitigate the risk of future harm. The knowledge of how clinical, worker, and organizational characteristics interact with this decision to provide ongoing child welfare services is not well integrated in the research literature. Using secondary data from the Canadian Incidence Study of Reported Child Abuse and Neglect-2008, this study's primary objective is to understand the relationship of clinical, worker, and organizational characteristics to the decision to transfer a case to ongoing child welfare services and their relative contribution to the transfer decision in Canada. Findings indicate that several clinical level variables are associated with families receiving ongoing services. Additionally, organizational factors, such as type of services offered by the organization and the number of employee support programs available to workers, significantly predicted the decision to transfer a case to ongoing services. While no worker factors, such as education, amount of training, experience, or caseload, were associated with ongoing service receipt, the intraclass correlation coefficient of the final three-level parsimonious model indicated substantial clustering at the worker level. Results indicate that Canadian child welfare workers make decisions differently based on factors not available in the current study and that what would be deemed as important worker characteristics do not necessarily predict this outcome. Findings and implications for future research are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

PubMed

Miklós, István; Zádori, Zoltán

2012-02-01

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

Positive Evolutionary Selection of an HD Motif on Alzheimer Precursor Protein Orthologues Suggests a Functional Role

PubMed Central

Miklós, István; Zádori, Zoltán

2012-01-01

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the “transcription binding site turnover.” CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs. PMID:22319430

Impact of selected troposphere models on Precise Point Positioning convergence

NASA Astrophysics Data System (ADS)

Kalita, Jakub; Rzepecka, Zofia

2016-04-01

The Precise Point Positioning (PPP) absolute method is currently intensively investigated in order to reach fast convergence time. Among various sources that influence the convergence of the PPP, the tropospheric delay is one of the most important. Numerous models of tropospheric delay are developed and applied to PPP processing. However, with rare exceptions, the quality of those models does not allow fixing the zenith path delay tropospheric parameter, leaving difference between nominal and final value to the estimation process. Here we present comparison of several PPP result sets, each of which based on different troposphere model. The respective nominal values are adopted from models: VMF1, GPT2w, MOPS and ZERO-WET. The PPP solution admitted as reference is based on the final troposphere product from the International GNSS Service (IGS). The VMF1 mapping function was used for all processing variants in order to provide capability to compare impact of applied nominal values. The worst case initiates zenith wet delay with zero value (ZERO-WET). Impact from all possible models for tropospheric nominal values should fit inside both IGS and ZERO-WET border variants. The analysis is based on data from seven IGS stations located in mid-latitude European region from year 2014. For the purpose of this study several days with the most active troposphere were selected for each of the station. All the PPP solutions were determined using gLAB open-source software, with the Kalman filter implemented independently by the authors of this work. The processing was performed on 1 hour slices of observation data. In addition to the analysis of the output processing files, the presented study contains detailed analysis of the tropospheric conditions for the selected data. The overall results show that for the height component the VMF1 model outperforms GPT2w and MOPS by 35-40% and ZERO-WET variant by 150%. In most of the cases all solutions converge to the same values during first

Autonomous site selection and instrument positioning for sample acquisition

NASA Astrophysics Data System (ADS)

Shaw, A.; Barnes, D.; Pugh, S.

The European Space Agency Aurora Exploration Program aims to establish a European long-term programme for the exploration of Space, culminating in a human mission to space in the 2030 timeframe. Two flagship missions, namely Mars Sample Return and ExoMars, have been proposed as recognised steps along the way. The Exomars Rover is the first of these flagship missions and includes a rover carrying the Pasteur Payload, a mobile exobiology instrumentation package, and the Beagle 2 arm. The primary objective is the search for evidence of past or present life on mars, but the payload will also study the evolution of the planet and the atmosphere, look for evidence of seismological activity and survey the environment in preparation for future missions. The operation of rovers in unknown environments is complicated, and requires large resources not only on the planet but also in ground based operations. Currently, this can be very labour intensive, and costly, if large teams of scientists and engineers are required to assess mission progress, plan mission scenarios, and construct a sequence of events or goals for uplink. Furthermore, the constraints in communication imposed by the time delay involved over such large distances, and line-of-sight required, make autonomy paramount to mission success, affording the ability to operate in the event of communications outages and be opportunistic with respect to scientific discovery. As part of this drive to reduce mission costs and increase autonomy the Space Robotics group at the University of Wales, Aberystwyth is researching methods of autonomous site selection and instrument positioning, directly applicable to the ExoMars mission. The site selection technique used builds on the geometric reasoning algorithms used previously for localisation and navigation [Shaw 03]. It is proposed that a digital elevation model (DEM) of the local surface, generated during traverse and without interaction from ground based operators, can be

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.

Evolution of the pygmy phenotype: evidence of positive selection fro genome-wide scans in African, Asian, and Melanesian pygmies.

PubMed

Migliano, Andrea Bamberg; Romero, Irene Gallego; Metspalu, Mait; Leavesley, Matthew; Pagani, Luca; Antao, Tiago; Huang, Da-Wei; Sherman, Brad T; Siddle, Katharine; Scholes, Clarissa; Hudjashov, Georgi; Kaitokai, Elton; Babalu, Avis; Belatti, Maggie; Cagan, Alex; Hopkinshaw, Byrony; Shaw, Colin; Nelis, Mari; Metspalu, Ene; Mägi, Reedik; Lempicki, Richard A; Villems, Richard; Lahr, Marta Mirazon; Kivisild, Toomas

2013-01-01

Human pygmy populations inhabit different regions of the world, from Africa to Melanesia. In Asia, short-statured populations are often referred to as "negritos." Their short stature has been interpreted as a consequence of thermoregulatory, nutritional, and/or locomotory adaptations to life in tropical forests. A more recent hypothesis proposes that their stature is the outcome of a life history trade-off in high-mortality environments, where early reproduction is favored and, consequently, early sexual maturation and early growth cessation have coevolved. Some serological evidence of deficiencies in the growth hormone/insulin-like growth factor axis have been previously associated with pygmies' short stature. Using genome-wide single-nucleotide polymorphism genotype data, we first tested whether different negrito groups living in the Philippines and Papua New Guinea are closely related and then investigated genomic signals of recent positive selection in African, Asian, and Papuan pygmy populations. We found that negritos in the Philippines and Papua New Guinea are genetically more similar to their nonpygmy neighbors than to one another and have experienced positive selection at different genes. These results indicate that geographically distant pygmy groups are likely to have evolved their short stature independently. We also found that selection on common height variants is unlikely to explain their short stature and that different genes associated with growth, thyroid function, and sexual development are under selection in different pygmy groups. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.

Long-term recovery trajectory after stroke: an ongoing negotiation between body, participation and self.

PubMed

Arntzen, Cathrine; Borg, Tove; Hamran, Torunn

2015-01-01

Research has mainly focused on the first year of recovery trajectory after stroke, but there is limited knowledge about how stroke survivors manage their long-term everyday lives. This study seeks to fill this gap by exploring the long-term (1-13 years) negotiations of stroke survivors when they experience progress, wellbeing and faith in the future. Repeated in-depth interviews were conducted with nine people living with moderate impairment after stroke and their closest relatives. Concepts from phenomenology and critical psychology constituted the frame of reference of the study. The long-term stroke recovery trajectory can be understood as a process of struggling to overcome tensions between three phenomena under ongoing change: the lived body, participation in everyday life and sense of self. During the recovery process, stroke survivors experience progress, well-being and faith in the future when moving towards renewed relationships, characterised by (1) a modified habitual body, (2) repositioned participation in specific everyday life contexts and (3) a transformed sense of self. This study stresses the importance of developing new forms of professional support during the long-term recovery trajectory, to stimulate and increase interaction and coherence in the relationship between the stroke survivor's bodily perception, participation in everyday life and sense of self. The study deepening how the long-term recovery trajectory after stroke is about ongoing embodied, practical and socially situated negotiations. The study demonstrates that the recovery trajectory is a long term process of learning where the stroke survivor, as an embodied agent, gradually modifies new bodily habits, re-position participation and transforming of the self. Health personnel are usually available in the acute and early rehabilitation period. The three phenomenons under ongoing change; "body", "participation" and "self" are at this point just about being moved toward a renewed and

Use of a novel saline/bipolar radiofrequency energy instrument as an adjunct for arresting ongoing solid organ surface and laceration bleeding in critically injured patients.

PubMed

Ball, Chad G; Campbell, Andre; Grondin, Sean C; Dixon, Elijah; DuBose, Joseph; McBeth, Paul B; Lall, Rohan

2016-09-01

Solid organ (liver, spleen and kidney) haemorrhage is often life threatening and can be difficult to stop in critically ill patients. Traditional techniques for arresting this ongoing bleeding include coagulation by high voltage cautery (Bovie), topical haemostatic application, and the delivery of ignited argon gas. The goal of this study was to evaluate the efficacy of a new energy device for arresting persistent solid organ haemorrhage. A novel instrument utilizing bipolar radiofrequency (RF) energy which acts to ignite/boil dripping saline from a simple hand piece was employed to arrest ongoing bleeding from solid organ injuries at 2 high volume, level 1 trauma centres. This instrument is extrapolated from experience within elective hepatic resections. Standard statistics were employed (p<0.05=significant). From January 2013 to January 2015, 36 severely injured patients (mean injury severity score=31; blunt mechanisms=32/36 (89%)) underwent use of this new saline/RF energy instrument to arrest ongoing haemorrhage from the liver (29), spleen (5) and kidney (2). Of these patients, 25 received instrument use during an initial laparotomy, while 11 patients underwent use following removal of sponges during a return laparotomy after an initial damage control procedure. Success in arresting ongoing haemorrhage was 97% (35/36) in these highly selected cases. The surgeons reported an 'ease of use' score of 4.9 out of 5. No postoperative complications (including delayed haemorrhage) were noted as a direct result of the energy instrument. This simple saline/RF energy instrument has the potential to arrest ongoing solid organ surface/capsular bleeding, as well as moderate haemorrhage associated with deep lacerations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ongoing adverse mental health impact of the earthquake sequence in Christchurch, New Zealand.

PubMed

Spittlehouse, Janet K; Joyce, Peter R; Vierck, Esther; Schluter, Philip J; Pearson, John F

2014-08-01

In September 2010 Christchurch, New Zealand, was struck by a 7.1 magnitude earthquake, followed by a prolonged sequence of significant aftershocks including a fatal aftershock in February 2011. Christchurch City has experienced widespread damage, ongoing disruption and building demolitions resulting in many difficulties for the residents of the Christchurch area. We explore what impact the earthquakes have had on the mental and physical health of a random sample of 50-year-olds who live in the Christchurch area. The 295 participants were selected from the electoral rolls for participation in the CHALICE study, a longitudinal study of ageing. Self-reported health status was assessed using the standardised Short Form 36 version 2 health survey (SF-36v2), a 36-item questionnaire, and results from the eight subscales compared to a national health survey. Mood disorders were assessed and the results were compared to other local and national studies. Since the onset of the earthquakes and throughout the study period, participating middle-aged Christchurch residents have mean SF-36v2 scores significantly lower than population norms in the mental health, vitality, social functioning and role-emotional subscales (Cohen's d ranged from -0.270 to -0.357, all p < 0.001), while there was no evidence of reduced physical health. Rates of current major depressive disorder were 7.5% in the earthquake survivors compared to 5.1% and 3.7% in other historical, local and national surveys. Similarly, bipolar disorder prevalence was 2.8% in the earthquake survivors compared to 2.2% and 1.4% in other studies. Eighteen months after the first earthquake the significant adverse impact on mental health clearly continues. The ongoing provision of additional mental health services and consideration of these adverse mental health effects in relation to other social policies remains necessary and fundamental. © The Royal Australian and New Zealand College of Psychiatrists 2014.

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

PubMed

Moxley, Jerad H; Charness, Neil

2013-10-01

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

Feature selection in feature network models: finding predictive subsets of features with the Positive Lasso.

PubMed

Frank, Laurence E; Heiser, Willem J

2008-05-01

A set of features is the basis for the network representation of proximity data achieved by feature network models (FNMs). Features are binary variables that characterize the objects in an experiment, with some measure of proximity as response variable. Sometimes features are provided by theory and play an important role in the construction of the experimental conditions. In some research settings, the features are not known a priori. This paper shows how to generate features in this situation and how to select an adequate subset of features that takes into account a good compromise between model fit and model complexity, using a new version of least angle regression that restricts coefficients to be non-negative, called the Positive Lasso. It will be shown that features can be generated efficiently with Gray codes that are naturally linked to the FNMs. The model selection strategy makes use of the fact that FNM can be considered as univariate multiple regression model. A simulation study shows that the proposed strategy leads to satisfactory results if the number of objects is less than or equal to 22. If the number of objects is larger than 22, the number of features selected by our method exceeds the true number of features in some conditions.

Visually Evoked Spiking Evolves While Spontaneous Ongoing Dynamics Persist

PubMed Central

Huys, Raoul; Jirsa, Viktor K.; Darokhan, Ziauddin; Valentiniene, Sonata; Roland, Per E.

2016-01-01

Neurons in the primary visual cortex spontaneously spike even when there are no visual stimuli. It is unknown whether the spiking evoked by visual stimuli is just a modification of the spontaneous ongoing cortical spiking dynamics or whether the spontaneous spiking state disappears and is replaced by evoked spiking. This study of laminar recordings of spontaneous spiking and visually evoked spiking of neurons in the ferret primary visual cortex shows that the spiking dynamics does not change: the spontaneous spiking as well as evoked spiking is controlled by a stable and persisting fixed point attractor. Its existence guarantees that evoked spiking return to the spontaneous state. However, the spontaneous ongoing spiking state and the visual evoked spiking states are qualitatively different and are separated by a threshold (separatrix). The functional advantage of this organization is that it avoids the need for a system reorganization following visual stimulation, and impedes the transition of spontaneous spiking to evoked spiking and the propagation of spontaneous spiking from layer 4 to layers 2–3. PMID:26778982

Direct evidence for a position input to the smooth pursuit system.

PubMed

Blohm, Gunnar; Missal, Marcus; Lefèvre, Philippe

2005-07-01

When objects move in our environment, the orientation of the visual axis in space requires the coordination of two types of eye movements: saccades and smooth pursuit. The principal input to the saccadic system is position error, whereas it is velocity error for the smooth pursuit system. Recently, it has been shown that catch-up saccades to moving targets are triggered and programmed by using velocity error in addition to position error. Here, we show that, when a visual target is flashed during ongoing smooth pursuit, it evokes a smooth eye movement toward the flash. The velocity of this evoked smooth movement is proportional to the position error of the flash; it is neither influenced by the velocity of the ongoing smooth pursuit eye movement nor by the occurrence of a saccade, but the effect is absent if the flash is ignored by the subject. Furthermore, the response started around 85 ms after the flash presentation and decayed with an average time constant of 276 ms. Thus this is the first direct evidence of a position input to the smooth pursuit system. This study shows further evidence for a coupling between saccadic and smooth pursuit systems. It also suggests that there is an interaction between position and velocity error signals in the control of more complex movements.

Diagnosis and Treatment of ALK Positive NSCLC

PubMed Central

Arbour, Kathryn C.; Riely, Gregory J.

2016-01-01

Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK driven tumor formation. Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors such as crizotinib, ceritinib, and alectinib. Resistance to these kinase inhibitors occurs through a number of mechanisms, resulting in ongoing clinical challenges. This review gives an overview of the biology of ALK positive lung cancer, methods for diagnosing ALK positive NSCLC, current FDA approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance. PMID:27912826

Multilevel Selection Theory and the Evolutionary Functions of Transposable Elements.

PubMed

Brunet, Tyler D P; Doolittle, W Ford

2015-08-06

One of several issues at play in the renewed debate over "junk DNA" is the organizational level at which genomic features might be seen as selected, and thus to exhibit function, as etiologically defined. The intuition frequently expressed by molecular geneticists that junk DNA is functional because it serves to "speed evolution" or as an "evolutionary repository" could be recast as a claim about selection between species (or clades) rather than within them, but this is not often done. Here, we review general arguments for the importance of selection at levels above that of organisms in evolution, and develop them further for a common genomic feature: the carriage of transposable elements (TEs). In many species, not least our own, TEs comprise a large fraction of all nuclear DNA, and whether they individually or collectively contribute to fitness--or are instead junk--is a subject of ongoing contestation. Even if TEs generally owe their origin to selfish selection at the lowest level (that of genomes), their prevalence in extant organisms and the prevalence of extant organisms bearing them must also respond to selection within species (on organismal fitness) and between species (on rates of speciation and extinction). At an even higher level, the persistence of clades may be affected (positively or negatively) by TE carriage. If indeed TEs speed evolution, it is at these higher levels of selection that such a function might best be attributed to them as a class. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations.

PubMed

Hermida-Carrera, Carmen; Fares, Mario A; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo; Galmés, Jeroni

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML.

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations

PubMed Central

Hermida-Carrera, Carmen; Fares, Mario A.; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V.; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML. PMID:28859145

DIESEL EXHAUST EXPOSURE INCREASES SEVERITY OF AN ONGOING INFLUENZA INFECTION

EPA Science Inventory

Numerous studies have shown that air pollutants including diesel exhaust (DE) alter host defense responses, resulting in decreased resistance to respiratory infection. The purpose of this study was to evaluate the effects of DE exposure on the severity of an ongoing influenza in...

Dynamics of Multistable States during Ongoing and Evoked Cortical Activity

PubMed Central

Mazzucato, Luca

2015-01-01

Single-trial analyses of ensemble activity in alert animals demonstrate that cortical circuits dynamics evolve through temporal sequences of metastable states. Metastability has been studied for its potential role in sensory coding, memory, and decision-making. Yet, very little is known about the network mechanisms responsible for its genesis. It is often assumed that the onset of state sequences is triggered by an external stimulus. Here we show that state sequences can be observed also in the absence of overt sensory stimulation. Analysis of multielectrode recordings from the gustatory cortex of alert rats revealed ongoing sequences of states, where single neurons spontaneously attain several firing rates across different states. This single-neuron multistability represents a challenge to existing spiking network models, where typically each neuron is at most bistable. We present a recurrent spiking network model that accounts for both the spontaneous generation of state sequences and the multistability in single-neuron firing rates. Each state results from the activation of neural clusters with potentiated intracluster connections, with the firing rate in each cluster depending on the number of active clusters. Simulations show that the model's ensemble activity hops among the different states, reproducing the ongoing dynamics observed in the data. When probed with external stimuli, the model predicts the quenching of single-neuron multistability into bistability and the reduction of trial-by-trial variability. Both predictions were confirmed in the data. Together, these results provide a theoretical framework that captures both ongoing and evoked network dynamics in a single mechanistic model. PMID:26019337

Unexplained infertility: overall ongoing pregnancy rate and mode of conception.

PubMed

Brandes, M; Hamilton, C J C M; van der Steen, J O M; de Bruin, J P; Bots, R S G M; Nelen, W L D M; Kremer, J A M

2011-02-01

Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility. In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception. Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history. Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

Ethanol-dispersed and antibody-conjugated polymer nanofibers for the selective capture and 3-dimensional culture of EpCAM-positive cells.

PubMed

Yoon, Junghyo; Yoon, Hee-Sook; Shin, Yoojin; Kim, Sanghyun; Ju, Youngjun; Kim, Jungbae; Chung, Seok

2017-07-01

Electrospun and ethanol-dispersed polystyrene-poly(styrene-co-maleic anhydride) (PS-PSMA) nanofibers (NFs) were used as a platform for the selective capture and three-dimensional culture of EpCAM-positive cells in cell culture medium and whole blood. The NFs were treated with streptavidin to facilitate bond formation between the amino groups of streptavidin and the maleic anhydride groups of the NFs. A biotinylated anti-EpCAM monoclonal antibody (mAb) was attached to the streptavidin-conjugated NFs via the selective binding of streptavidin and biotin. Upon simple mixing and shaking with EpCAM-positive cancer cells in a wide concentration range from 10 to 1000,000 cells per 10mL, the mAb-attached NFs (mAb-NFs) captured the Ep-CAM positive cells in an efficiency of 59%-67% depending on initial cell concentrations, with minor mechanical capture of 14%-36%. Captured cells were directly cultured, forming cell aggregates, in the NF matrix, which ensures the cell proliferation and follow-up analysis. Furthermore, the capture capacity of mAb-NFs was assessed in the presence of whole blood and blood lysates, indicating cluster formation that captured target cells. It is anticipated that the antibody-attached NFs can be employed for the capture and analysis of very rare EpCAM positive circulating cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

7 CFR 25.403. - Ongoing 2-year work plan requirement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 25.403. Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... conditional upon the designation of the community as an Empowerment Zone; and (iv) Documentation of...

7 CFR 25.403. - Ongoing 2-year work plan requirement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 25.403. Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... conditional upon the designation of the community as an Empowerment Zone; and (iv) Documentation of...

7 CFR 25.403. - Ongoing 2-year work plan requirement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 25.403. Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... conditional upon the designation of the community as an Empowerment Zone; and (iv) Documentation of...

7 CFR 25.403. - Ongoing 2-year work plan requirement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 25.403. Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... conditional upon the designation of the community as an Empowerment Zone; and (iv) Documentation of...

Ongoing Mars Missions: Extended Mission Plans

NASA Astrophysics Data System (ADS)

Zurek, Richard; Diniega, Serina; Crisp, Joy; Fraeman, Abigail; Golombek, Matt; Jakosky, Bruce; Plaut, Jeff; Senske, David A.; Tamppari, Leslie; Thompson, Thomas W.; Vasavada, Ashwin R.

2016-10-01

Many key scientific discoveries in planetary science have been made during extended missions. This is certainly true for the Mars missions both in orbit and on the planet's surface. Every two years, ongoing NASA planetary missions propose investigations for the next two years. This year, as part of the 2016 Planetary Sciences Division (PSD) Mission Senior Review, the Mars Odyssey (ODY) orbiter project submitted a proposal for its 7th extended mission, the Mars Exploration Rover (MER-B) Opportunity submitted for its 10th, the Mars Reconnaissance Orbiter (MRO) for its 4th, and the Mars Science Laboratory (MSL) Curiosity rover and the Mars Atmosphere and Volatile Evolution (MVN) orbiter for their 2nd extended missions, respectively. Continued US participation in the ongoing Mars Express Mission (MEX) was also proposed. These missions arrived at Mars in 2001, 2004, 2006, 2012, 2014, and 2003, respectively. Highlights of proposed activities include systematic observations of the surface and atmosphere in twilight (early morning and late evening), building on a 13-year record of global mapping (ODY); exploration of a crater rim gully and interior of Endeavour Crater, while continuing to test what can and cannot be seen from orbit (MER-B); refocused observations of ancient aqueous deposits and polar cap interiors, while adding a 6th Mars year of change detection in the atmosphere and the surface (MRO); exploration and sampling by a rover of mineralogically diverse strata of Mt. Sharp and of atmospheric methane in Gale Crater (MSL); and further characterization of atmospheric escape under different solar conditions (MVN). As proposed, these activities follow up on previous discoveries (e.g., recurring slope lineae, habitable environments), while expanding spatial and temporal coverage to guide new detailed observations. An independent review panel evaluated these proposals, met with project representatives in May, and made recommendations to NASA in June 2016. In this

Transcriptome Sequencing and Positive Selected Genes Analysis of Bombyx mandarina

PubMed Central

Wu, Yuqian; Long, Renwen; Liu, Chun; Xia, Qingyou

2015-01-01

The wild silkworm Bombyx mandarina is widely believed to be an ancestor of the domesticated silkworm, Bombyx mori. Silkworms are often used as a model for studying the mechanism of species domestication. Here, we performed transcriptome sequencing of the wild silkworm using an Illumina HiSeq2000 platform. We produced 100,004,078 high-quality reads and assembled them into 50,773 contigs with an N50 length of 1764 bp and a mean length of 941.62 bp. A total of 33,759 unigenes were identified, with 12,805 annotated in the Nr database, 8273 in the Pfam database, and 9093 in the Swiss-Prot database. Expression profile analysis found significant differential expression of 1308 unigenes between the middle silk gland (MSG) and posterior silk gland (PSG). Three sericin genes (sericin 1, sericin 2, and sericin 3) were expressed specifically in the MSG and three fibroin genes (fibroin-H, fibroin-L, and fibroin/P25) were expressed specifically in the PSG. In addition, 32,297 Single-nucleotide polymorphisms (SNPs) and 361 insertion-deletions (INDELs) were detected. Comparison with the domesticated silkworm p50/Dazao identified 5,295 orthologous genes, among which 400 might have experienced or to be experiencing positive selection by Ka/Ks analysis. These data and analyses presented here provide insights into silkworm domestication and an invaluable resource for wild silkworm genomics research. PMID:25806526

Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches.

PubMed

Careau, Vincent; Bininda-Emonds, Olaf R P; Ordonez, Genesis; Garland, Theodore

2012-09-01

Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

Ongoing contraception after use of emergency contraception from a specialist contraceptive service.

PubMed

Cameron, Sharon T; Glasier, Anna; Johnstone, Anne; Rae, Leanne

2011-10-01

A consultation for emergency contraception (EC) gives way to an opportunity to provide women with an ongoing effective method of contraception. A review of the case notes of women seeking EC from a large family planning clinic in Edinburgh, Scotland, was conducted to determine what percentage of women were provided with an effective method of ongoing contraception. Case notes of 460 women presenting for EC over a 2-year period were reviewed. Women were of mean age 26 years (range 15-49 years) and presented because they had used no contraception (47%), experienced condom failure (42%) or missed oral contraceptive pills (9%). Only 2% (n=11) were given an intrauterine device for EC. All women who had missed contraceptive pills prior to taking EC opted to continue this method. Only 23% (n=89) of women using no method or condoms at EC received supplies of an effective contraceptive method (pills, patch, injectable). Two thirds (n=263) of the women chose condoms for ongoing contraception. Research is required to develop strategies to improve the uptake of effective contraception after EC. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Associations between Neighborhood Walkability and Incident and Ongoing Asthma in Children.

PubMed

Simons, Elinor; Dell, Sharon D; Moineddin, Rahim; To, Teresa

2018-06-01

Childhood asthma has shown variable associations with children's physical activity. Neighborhood walkability captures community features that promote walking and is protective against some chronic conditions, such as obesity and diabetes. We evaluated associations between home neighborhood walkability and incident and ongoing childhood asthma. In this population-based cohort study, we used prospectively collected administrative healthcare data for the Province of Ontario housed at the Institute for Clinical Evaluative Sciences. We followed an administrative data cohort of 326,383 Toronto children born between 1997 and 2003, inclusive, until ages 8-15 years. Home neighborhood walkability quintile was measured using a validated walkability index with four dimensions: population density, dwelling density, access to retail and services, and street connectivity. Incident asthma was defined by time of entry into the validated Ontario Asthma Surveillance Information System database, which requires two outpatient visits for asthma within two consecutive years or any hospitalization for asthma and follows children with asthma longitudinally starting at any age. Associations between walkability and incident asthma were examined using Cox proportional hazards models. Associations between ongoing asthma and walkability in each year of life were examined using generalized linear mixed models. Twenty-one percent of children (n = 69,628) developed incident asthma and were followed longitudinally in the Ontario Asthma Surveillance Information System database. Low birth home neighborhood walkability was associated with an increased incidence of asthma (hazard ratio, 1.11; 95% confidence interval, 1.08-1.14). Among children with asthma, low walkability in a given year of a child`s life was associated with greater odds of ongoing asthma in the same year (odds ratio, 1.12; 95% confidence interval, 1.09-1.14). Children living in neighborhoods with low walkability were at increased

A model of metastable dynamics during ongoing and evoked cortical activity

NASA Astrophysics Data System (ADS)

La Camera, Giancarlo

The dynamics of simultaneously recorded spike trains in alert animals often evolve through temporal sequences of metastable states. Little is known about the network mechanisms responsible for the genesis of such sequences, or their potential role in neural coding. In the gustatory cortex of alert rates, state sequences can be observed also in the absence of overt sensory stimulation, and thus form the basis of the so-called `ongoing activity'. This activity is characterized by a partial degree of coordination among neurons, sharp transitions among states, and multi-stability of single neurons' firing rates. A recurrent spiking network model with clustered topology can account for both the spontaneous generation of state sequences and the (network-generated) multi-stability. In the model, each network state results from the activation of specific neural clusters with potentiated intra-cluster connections. A mean field solution of the model shows a large number of stable states, each characterized by a subset of simultaneously active clusters. The firing rate in each cluster during ongoing activity depends on the number of active clusters, so that the same neuron can have different firing rates depending on the state of the network. Because of dense intra-cluster connectivity and recurrent inhibition, in finite networks the stable states lose stability due to finite size effects. Simulations of the dynamics show that the model ensemble activity continuously hops among the different states, reproducing the ongoing dynamics observed in the data. Moreover, when probed with external stimuli, the model correctly predicts the quenching of single neuron multi-stability into bi-stability, the reduction of dimensionality of the population activity, the reduction of trial-to-trial variability, and a potential role for metastable states in the anticipation of expected events. Altogether, these results provide a unified mechanistic model of ongoing and evoked cortical dynamics

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

PubMed

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

2015-05-13

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

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

PubMed

Kuhn, Alexandre; Ong, Yao Min; Cheng, Ching-Yu; Wong, Tien Yin; Quake, Stephen R; Burkholder, William F

2014-06-03

Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.

The Sonographic Appearance of Spinal Fluid at Clinically Selected Interspaces in Sitting Versus Lateral Positions.

PubMed

Vitberg, Yaffa M; Tseng, Peggy; Kessler, David O

2018-05-01

Our objective was to describe the sonographic appearance of fluid at clinically selected interspinous spaces and see if additional interspaces could be identified as suitable and safe targets for needle insertion. We also measured the reproducibility of fluid measurements and assessed for positional differences. A prospective convenience sample of infants younger than 3 months was enrolled in the pediatric emergency department. Excluded were clinically unstable infants or those with spinal dysraphism. Infants were first held in standard lateral lumbar puncture position. Pediatric emergency medicine (PEM) physicians marked infants' backs at the level they would insert a needle using the landmark palpation technique. A PEM sonologist imaged and measured the spinal fluid in 2 orthogonal planes at this marked level in lateral then sitting positions. Fluid measurements were repeated by a second blinded PEM sonologist. Forty-six infants were enrolled. Ultrasound verified the presence of fluid at the marked level as determined by the landmark palpation technique in 98% of cases. Ultrasound identified additional suitable spaces 1 space higher (82%) and 2 spaces higher (41%). Intraclass correlation coefficient of all measurements was excellent (>0.85), with differences noted for sitting versus lateral position in mean area of fluid 0.34 mm versus 0.31 mm (difference, 0.03; 95% confidence interval [CI], 0.005-0.068), dorsal fluid pocket 0.23 mm versus 0.15 mm (difference, 0.08; 95% CI, 0.031-0.123), and nerve root-to-canal ratio 0.44 versus 0.51 (difference, 0.07; 95% CI, 0.004-0.117). Ultrasound can verify the presence of fluid at interspaces determined by the landmark palpation technique and identify additional suitable spaces at higher levels. There were statistically greater fluid measurements in sitting versus lateral positions. These novel fluid measurements were shown to be reliable.

ASASSN-17oz: Discovery of an Unusual, Ongoing Stellar Outburst

NASA Astrophysics Data System (ADS)

Jayasinghe, T.; Stanek, K. Z.; Kochanek, C. S.; Prieto, J. L.; Shields, J. V.; Thompson, T. A.; Dong, Subo; Shappee, B. J.; Holoien, T. W.-S.; Falco, E.; Leadbeater, R.; Rupert, J.; Brimacombe, J.; Koff, R. A.; Post, R. S.

2017-11-01

During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN, Shappee et al. 2014, Kochanek et al. 2017), using data from the quadruple 14-cm "Brutus" (Haleakala, Hawaii) and "Leavitt" (Fort Davis, Texas) telescopes, we discovered an unusual transient source that is indicative of a stellar outburst.

Cloning and characterization of wnt4a gene and evidence for positive selection in half-smooth tongue sole (Cynoglossus semilaevis).

PubMed

Hu, Qiaomu; Zhu, Ying; Liu, Yang; Wang, Na; Chen, Songlin

2014-11-24

Wnt4 gene plays a role in developmental processes in mammals. However, little is known regarding its function in teleosts. We cloned and characterized the full-length half-smooth tongue sole (Cynoglossus semilaevis) wnt4a gene (CS-wnt4a). CS-wnt4a cDNA was 1746 bp in length encoding 353aa. CS-wnt4a expression level was highest in the testis, and gradually increased in the developing gonads until 1 year of age. In situ hybridization revealed that CS-wnt4a expression level was highest in stage II oocytes and sperm in the adult ovary and testis, respectively. CS-wnt4a expression level was significantly up-regulated in the gonads after exposure to high temperature. The level of methylation of the CS-wnt4a first exon was negatively correlated with the expression of CS-wnt4a. The branch-site model suggested that vertebrate wnt4a differed significantly from that of wnt4b, and that the selective pressures differed between ancestral aquatic and terrestrial organisms. Two positively selected sites were found in the ancestral lineages of teleost fish, but none in the ancestral lineages of mammals. One positively selected site was located on the α-helices of the 3D structure, the other on the random coil. Our results are of value for further study of the function of wnt4 and the mechanism of selection.

Cloning and characterization of wnt4a gene and evidence for positive selection in half-smooth tongue sole (Cynoglossus semilaevis)

NASA Astrophysics Data System (ADS)

Hu, Qiaomu; Zhu, Ying; Liu, Yang; Wang, Na; Chen, Songlin

2014-11-01

Wnt4 gene plays a role in developmental processes in mammals. However, little is known regarding its function in teleosts. We cloned and characterized the full-length half-smooth tongue sole (Cynoglossus semilaevis) wnt4a gene (CS-wnt4a). CS-wnt4a cDNA was 1746 bp in length encoding 353aa. CS-wnt4a expression level was highest in the testis, and gradually increased in the developing gonads until 1 year of age. In situ hybridization revealed that CS-wnt4a expression level was highest in stage II oocytes and sperm in the adult ovary and testis, respectively. CS-wnt4a expression level was significantly up-regulated in the gonads after exposure to high temperature. The level of methylation of the CS-wnt4a first exon was negatively correlated with the expression of CS-wnt4a. The branch-site model suggested that vertebrate wnt4a differed significantly from that of wnt4b, and that the selective pressures differed between ancestral aquatic and terrestrial organisms. Two positively selected sites were found in the ancestral lineages of teleost fish, but none in the ancestral lineages of mammals. One positively selected site was located on the α-helices of the 3D structure, the other on the random coil. Our results are of value for further study of the function of wnt4 and the mechanism of selection.

Avionics Architectures for Exploration: Ongoing Efforts in Human Spaceflight

NASA Technical Reports Server (NTRS)

Goforth, Montgomery B.; Ratliff, James E.; Hames, Kevin L.; Vitalpur, Sharada V.; Woodman, Keith L.

2014-01-01

The field of Avionics is advancing far more rapidly in terrestrial applications than in spaceflight applications. Spaceflight Avionics are not keeping pace with expectations set by terrestrial experience, nor are they keeping pace with the need for increasingly complex automation and crew interfaces as we move beyond Low Earth Orbit. NASA must take advantage of the strides being made by both space-related and terrestrial industries to drive our development and sustaining costs down. This paper describes ongoing efforts by the Avionics Architectures for Exploration (AAE) project chartered by NASA's Advanced Exploration Systems (AES) Program to evaluate new avionic architectures and technologies, provide objective comparisons of them, and mature selected technologies for flight and for use by other AES projects. The AAE project team includes members from most NASA centers, and from industry. It is our intent to develop a common core avionic system that has standard capabilities and interfaces, and contains the basic elements and functionality needed for any spacecraft. This common core will be scalable and tailored to specific missions. It will incorporate hardware and software from multiple vendors, and be upgradeable in order to infuse incremental capabilities and new technologies. It will maximize the use of reconfigurable open source software (e.g., Goddard Space Flight Center's (GSFC's) Core Flight Software (CFS)). Our long-term focus is on improving functionality, reliability, and autonomy, while reducing size, weight, and power. Where possible, we will leverage terrestrial commercial capabilities to drive down development and sustaining costs. We will select promising technologies for evaluation, compare them in an objective manner, and mature them to be available for future programs. The remainder of this paper describes our approach, technical areas of emphasis, integrated test experience and results as of mid-2014, and future plans. As a part of the AES

Ongoing training of community health workers in low-income andmiddle-income countries: a systematic scoping review of the literature.

PubMed

O'Donovan, James; O'Donovan, Charles; Kuhn, Isla; Sachs, Sonia Ehrlich; Winters, Niall

2018-04-28

Understanding the current landscape of ongoing training for community health workers (CHWs) in low-income and middle-income countries (LMICs) is important both for organisations responsible for their training, as well as researchers and policy makers. This scoping review explores this under-researched area by mapping the current delivery implementation and evaluation of ongoing training provision for CHWs in LMICs. Systematic scoping review. MEDLINE, Embase, AMED, Global Health, Web of Science, Scopus, ASSIA, LILACS, BEI and ERIC. Original studies focusing on the provision of ongoing training for CHWs working in a country defined as low income and middle income according to World Bank Group 2012 classification of economies. The scoping review found 35 original studies that met the inclusion criteria. Ongoing training activities for CHWs were described as supervision (n=19), inservice or refresher training (n=13) or a mixture of both (n=3). Although the majority of studies emphasised the importance of providing ongoing training, several studies reported no impact of ongoing training on performance indicators. The majority of ongoing training was delivered inperson; however, four studies reported the use of mobile technologies to support training delivery. The outcomes from ongoing training activities were measured and reported in different ways, including changes in behaviour, attitudes and practice measured in a quantitative manner (n=16), knowledge and skills (n=6), qualitative assessments (n=5) or a mixed methods approach combining one of the aforementioned modalities (n=8). This scoping review highlights the diverse range of ongoing training for CHWs in LMICs. Given the expansion of CHW programmes globally, more attention should be given to the design, delivery, monitoring and sustainability of ongoing training from a health systems strengthening perspective. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All

Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

PubMed Central

Gehrmann, Mathias K; Kimm, Melanie A; Stangl, Stefan; Schmid, Thomas E; Noël, Peter B; Rummeny, Ernst J; Multhoff, Gabriele

2015-01-01

Real-time imaging of small tumors is still one of the challenges in cancer diagnosis, prognosis, and monitoring of clinical outcome. Targeting novel biomarkers that are selectively expressed on a large variety of different tumors but not normal cells has the potential to improve the imaging capacity of existing methods such as computed tomography. Herein, we present a novel technique using cmHsp70.1 monoclonal antibody-conjugated spherical gold nanoparticles for quantification of the targeted uptake of gold nanoparticles into membrane Hsp70-positive tumor cells. Upon binding, cmHsp70.1-conjugated gold nanoparticles but not nanoparticles coupled to an isotype-matched IgG1 antibody or empty nanoparticles are rapidly taken up by highly malignant Hsp70 membrane-positive mouse tumor cells. After 24 hours, the cmHsp70.1-conjugated gold nanoparticles are found to be enriched in the perinuclear region. Specificity for membrane Hsp70 was shown by using an Hsp70 knockout tumor cell system. Toxic side effects of the cmHsp70.1-conjugated nanoparticles are not observed at a concentration of 1–10 µg/mL. Experiments are ongoing to evaluate whether cmHsp70.1 antibody-conjugated gold nanoparticles are suitable for the detection of membrane-Hsp70-positive tumors in vivo. PMID:26392771

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

PubMed

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

2015-11-01

Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a novel computational approach to test for selection in CD8(+) T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8(+) T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8(+) T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8(+) T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal

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

PubMed Central

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

2015-01-01

ABSTRACT Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. IMPORTANCE There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+ T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal

Incorporation of isotopic, fluorescent, and heavy-atom-modified nucleotides into RNAs by position-selective labeling of RNA.

PubMed

Liu, Yu; Holmstrom, Erik; Yu, Ping; Tan, Kemin; Zuo, Xiaobing; Nesbitt, David J; Sousa, Rui; Stagno, Jason R; Wang, Yun-Xing

2018-05-01

Site-specific incorporation of labeled nucleotides is an extremely useful synthetic tool for many structural studies (e.g., NMR, electron paramagnetic resonance (EPR), fluorescence resonance energy transfer (FRET), and X-ray crystallography) of RNA. However, specific-position-labeled RNAs >60 nt are not commercially available on a milligram scale. Position-selective labeling of RNA (PLOR) has been applied to prepare large RNAs labeled at desired positions, and all the required reagents are commercially available. Here, we present a step-by-step protocol for the solid-liquid hybrid phase method PLOR to synthesize 71-nt RNA samples with three different modification applications, containing (i) a 13 C 15 N-labeled segment; (ii) discrete residues modified with Cy3, Cy5, or biotin; or (iii) two iodo-U residues. The flexible procedure enables a wide range of downstream biophysical analyses using precisely localized functionalized nucleotides. All three RNAs were obtained in <2 d, excluding time for preparing reagents and optimizing experimental conditions. With optimization, the protocol can be applied to other RNAs with various labeling schemes, such as ligation of segmentally labeled fragments.

The Fukushima nuclear disaster is ongoing.

PubMed

Marks, Andrew R

2016-07-01

The 5th anniversary of the Fukushima disaster and the 30th anniversary of the Chernobyl disaster, the two most catastrophic nuclear accidents in history, both occurred recently. Images of Chernobyl are replete with the international sign of radioactive contamination (a circle with three broad spokes radiating outward in a yellow sign). In contrast, ongoing decontamination efforts at Fukushima lack international warnings about radioactivity. Decontamination workers at Fukushima appear to be poorly protected against radiation. It is almost as if the effort is to make the Fukushima problem disappear. A more useful response would be to openly acknowledge the monumental problems inherent in managing a nuclear plant disaster. Lessons from Chernobyl are the best predictors of what the Fukushima region of Japan is coping with in terms of health and environmental problems following a nuclear catastrophe.

Environmental impact of ongoing sources of metal contamination on remediated sediments

DOE PAGES

Knox, Anna Sophia; Paller, Michael H.; Milliken, Charles E.; ...

2016-04-29

One challenge to all remedial approaches for contaminated sediments is the continued influx of contaminants from uncontrolled sources following remediation. We investigated the effects of ongoing contamination in mesocosms employing sediments remediated by different types of active and passive caps and in-situ treatment. Our hypothesis was that the sequestering agents used in active caps and in situ treatment will bind elements (arsenic, chromium, cadmium, cobalt, copper, nickel, lead, selenium, and zinc) from ongoing sources thereby reducing their bioavailability and protecting underlying remediated sediments from recontamination. Most element concentrations in surface water remained significantly lower in mesocosms with apatite and mixedmore » amendment caps than in mesocosms with passive caps (sand), uncapped sediment, and spike solution throughout the 2520 hour experiment. Element concentrations were significantly higher in Lumbriculus variegatus from untreated sediment than in Lumbriculus from most active caps. Moreover, Pearson correlations between element concentrations in Lumbriculus and metal concentrations in the top 2.5 cm of sediment or cap measured by diffusive gradient in thin films (DGT) sediment probes were generally strong (as high as 0.98) and significant (p<0.05) for almost all tested elements. Metal concentrations in both Lumbriculus and sediment/cap were lowest in apatite, mixed amendment, and activated carbon treatments. Finally, these findings show that some active caps can protect remediated sediments by reducing the bioavailable pool of metals/metalloids in ongoing sources of contamination.« less

Amerindian-specific regions under positive selection harbour new lipid variants in Latinos

PubMed Central

Ko, Arthur; Cantor, Rita M.; Weissglas-Volkov, Daphna; Nikkola, Elina; Reddy, Prasad M. V. Linga; Sinsheimer, Janet S.; Pasaniuc, Bogdan; Brown, Robert; Alvarez, Marcus; Rodriguez, Alejandra; Rodriguez-Guillen, Rosario; Bautista, Ivette C.; Arellano-Campos, Olimpia; Muñoz-Hernández, Linda L.; Salomaa, Veikko; Kaprio, Jaakko; Jula, Antti; Jauhiainen, Matti; Heliövaara, Markku; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Perola, Markus; Lohmueller, Kirk E.; Matikainen, Niina; Taskinen, Marja-Riitta; Rodriguez-Torres, Maribel; Riba, Laura; Tusie-Luna, Teresa; Aguilar-Salinas, Carlos A.; Pajukanta, Päivi

2014-01-01

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican–Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans. PMID:24886709

Genomic resources and their influence on the detection of the signal of positive selection in genome scans.

PubMed

Manel, S; Perrier, C; Pratlong, M; Abi-Rached, L; Paganini, J; Pontarotti, P; Aurelle, D

2016-01-01

Genome scans represent powerful approaches to investigate the action of natural selection on the genetic variation of natural populations and to better understand local adaptation. This is very useful, for example, in the field of conservation biology and evolutionary biology. Thanks to Next Generation Sequencing, genomic resources are growing exponentially, improving genome scan analyses in non-model species. Thousands of SNPs called using Reduced Representation Sequencing are increasingly used in genome scans. Besides, genome sequences are also becoming increasingly available, allowing better processing of short-read data, offering physical localization of variants, and improving haplotype reconstruction and data imputation. Ultimately, genome sequences are also becoming the raw material for selection inferences. Here, we discuss how the increasing availability of such genomic resources, notably genome sequences, influences the detection of signals of selection. Mainly, increasing data density and having the information of physical linkage data expand genome scans by (i) improving the overall quality of the data, (ii) helping the reconstruction of demographic history for the population studied to decrease false-positive rates and (iii) improving the statistical power of methods to detect the signal of selection. Of particular importance, the availability of a high-quality reference genome can improve the detection of the signal of selection by (i) allowing matching the potential candidate loci to linked coding regions under selection, (ii) rapidly moving the investigation to the gene and function and (iii) ensuring that the highly variable regions of the genomes that include functional genes are also investigated. For all those reasons, using reference genomes in genome scan analyses is highly recommended. © 2015 John Wiley & Sons Ltd.

Effects of ongoing task context and target typicality on prospective memory performance: the importance of associative cueing

NASA Technical Reports Server (NTRS)

Nowinski, Jessica Lang; Dismukes, Key R.

2005-01-01

Two experiments examined whether prospective memory performance is influenced by contextual cues. In our automatic activation model, any information available at encoding and retrieval should aid recall of the prospective task. The first experiment demonstrated an effect of the ongoing task context; performance was better when information about the ongoing task present at retrieval was available at encoding. Performance was also improved by a strong association between the prospective memory target as it was presented at retrieval and the intention as it was encoded. Experiment 2 demonstrated boundary conditions of the ongoing task context effect, which implicate the association between the ongoing and prospective tasks formed at encoding as the source of the context effect. The results of this study are consistent with predictions based on automatic activation of intentions.

10 CFR 51.12 - Application of subpart to ongoing environmental work.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Application of subpart to ongoing environmental work. 51.12 Section 51.12 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act...

10 CFR 51.12 - Application of subpart to ongoing environmental work.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Application of subpart to ongoing environmental work. 51.12 Section 51.12 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act...

Hand-held dynamometer testing of the internal and external rotator musculature based on selected positions to establish normative data and unilateral ratios.

PubMed

Riemann, Bryan L; Davies, George J; Ludwig, Lauren; Gardenhour, Helen

2010-12-01

Objective documentation is needed of shoulder internal and external rotator strength using hand-held dynamometry in selected positions commonly used in a clinic. We compared strength measures and unilateral ratios between gender, limbs (dominant, nondominant), and 3 testing positions. We hypothesized that men would be stronger than women, the dominant shoulder would be stronger than the nondominant shoulder, and the seated neutral (0° adduction) and seated 30° abduction, 30° scaption, 30° diagonal (30°-30°-30°) positions would be stronger than the prone at 90°-90° position. Three positions (prone at 90°, seated at neutral, and seated at 30°-30°-30°) were evaluated in 181 individuals using hand-held dynamometry. Three separate 3-factor (limb by position by gender) analyses of variance were conducted on internal rotation, external rotation, and unilateral ratios. Although the dominant limb was significantly stronger (P < .001) than the nondominant for internal rotation, there was no difference for external rotation. The external rotators demonstrated significantly greater strength in the prone at 90° position compared with the seated at neutral (P = .001) and seated at 30°-30°-30° (P = .002) positions. The internal rotators demonstrated significantly greater (P = .036) strength in the neutral position than in the prone at 90° position for the women. The unilateral ratio of external rotators/internal rotators ranged from 86% to 99%. For the women, the prone at 90° ratio was significantly greater than seated at neutral (P = .001) and seated at 30°-30°-30° (P = .001) positions. Moderate strength relationships (r = 0.506 to 0.572) were revealed between body mass and all strength measures. The results of this study provide evidence to interpret normative data, bilateral comparisons and unilateral ratios of the internal/external rotators in the 3 selected positions. Because there are no differences between the seated at neutral and 30°-30°-30�

Dynamic nigrostriatal dopamine biases action selection

PubMed Central

Howard, Christopher D.; Li, Hao; Geddes, Claire E.; Jin, Xin

2017-01-01

Summary Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here, we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons, or optogenetic manipulation of dopamine concentration, alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions and have important implications for neurological disorders including Parkinson’s disease and substance dependence. PMID:28285820

Dynamic Nigrostriatal Dopamine Biases Action Selection.

PubMed

Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin

2017-03-22

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

Cao-Lormeau, Van-Mai; Lambrechts, Louis

2017-01-01

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

Retention of duplicated long-wavelength opsins in mosquito lineages by positive selection and differential expression.

PubMed

Giraldo-Calderón, Gloria I; Zanis, Michael J; Hill, Catherine A

2017-03-21

Opsins are light sensitive receptors associated with visual processes. Insects typically possess opsins that are stimulated by ultraviolet, short and long wavelength (LW) radiation. Six putative LW-sensitive opsins predicted in the yellow fever mosquito, Aedes aegypti and malaria mosquito, Anopheles gambiae, and eight in the southern house mosquito, Culex quinquefasciatus, suggest gene expansion in the Family Culicidae (mosquitoes) relative to other insects. Here we report the first detailed molecular and evolutionary analyses of LW opsins in three mosquito vectors, with a goal to understanding the molecular basis of opsin-mediated visual processes that could be exploited for mosquito control. Time of divergence estimates suggest that the mosquito LW opsins originated from 18 or 19 duplication events between 166.9/197.5 to 1.07/0.94 million years ago (MY) and that these likely occurred following the predicted divergence of the lineages Anophelinae and Culicinae 145-226 MY. Fitmodel analyses identified nine amino acid residues in the LW opsins that may be under positive selection. Of these, eight amino acids occur in the N and C termini and are shared among all three species, and one residue in TMIII was unique to culicine species. Alignment of 5' non-coding regions revealed potential Conserved Non-coding Sequences (CNS) and transcription factor binding sites (TFBS) in seven pairs of LW opsin paralogs. Our analyses suggest opsin gene duplication and residues possibly associated with spectral tuning of LW-sensitive photoreceptors. We explore two mechanisms - positive selection and differential expression mediated by regulatory units in CNS - that may have contributed to the retention of LW opsin genes in Culicinae and Anophelinae. We discuss the evolution of mosquito LW opsins in the context of major Earth events and possible adaptation of mosquitoes to LW-dominated photo environments, and implications for mosquito control strategies based on disrupting vision

Review of the Clinical and Biologic Aspects of Human Papillomavirus-Positive Squamous Cell Carcinomas of the Head and Neck

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

Blitzer, Grace C.; Smith, Molly A.; Harris, Stephen L.

Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seenmore » in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.« less

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

PubMed

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

2016-08-01

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

22 CFR 502.5 - Media or organization requests for ongoing subscriptions to broadcast quality agency program...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Media or organization requests for ongoing... BOARD OF GOVERNORS DOMESTIC REQUESTS FOR BROADCASTING BOARD OF GOVERNORS PROGRAM MATERIALS § 502.5 Media...) Upon request, the Agency may make program materials available on an ongoing basis to Media entities, or...

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

PubMed

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

2016-01-01

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

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory.

PubMed

Meier, Beat; Zimmermann, Thomas D

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

PubMed Central

Meier, Beat; Zimmermann, Thomas D.

2015-01-01

In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially. PMID:26082709

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. II. Effects on metrics and kinematics of ongoing gaze shifts to visual targets.

PubMed

Freedman, Edward G; Quessy, Stephan

2004-06-01

Saccade kinematics are altered by ongoing head movements. The hypothesis that a head movement command signal, proportional to head velocity, transiently reduces the gain of the saccadic burst generator (Freedman 2001, Biol Cybern 84:453-462) can account for this observation. Using electrical stimulation of the rhesus monkey nucleus reticularis gigantocellularis (NRG) to alter the head contribution to ongoing gaze shifts, two critical predictions of this gaze control hypothesis were tested. First, this hypothesis predicts that activation of the head command pathway will cause a transient reduction in the gain of the saccadic burst generator. This should alter saccade kinematics by initially reducing velocity without altering saccade amplitude. Second, because this hypothesis does not assume that gaze amplitude is controlled via feedback, the added head contribution (produced by NRG stimulation on the side ipsilateral to the direction of an ongoing gaze shift) should lead to hypermetric gaze shifts. At every stimulation site tested, saccade kinematics were systematically altered in a way that was consistent with transient reduction of the gain of the saccadic burst generator. In addition, gaze shifts produced during NRG stimulation were hypermetric compared with control movements. For example, when targets were briefly flashed 30 degrees from an initial fixation location, gaze shifts during NRG stimulation were on average 140% larger than control movements. These data are consistent with the predictions of the tested hypothesis, and may be problematic for gaze control models that rely on feedback control of gaze amplitude, as well as for models that do not posit an interaction between head commands and the saccade burst generator.

Older Adults Exposed to Ongoing versus Intense Time-Limited Missile Attacks: Differences in Symptoms of Posttraumatic Stress Disorder.

PubMed

Shrira, Amit; Shmotkin, Dov; Palgi, Yuval; Hoffman, Yaakov; Bodner, Ehud; Ben-Ezra, Menachem; Litwin, Howard

2017-01-01

The potentially different psychological effects of ongoing trauma vis-à-vis an intense time-limited exposure to trauma have not been examined in older adults. Therefore, this study examined posttraumatic stress disorder (PTSD) symptoms and their health concomitants in two groups of older adults in Israel: those exposed to ongoing missile attacks and those exposed to an intense time-limited period of missile attacks. In the third administration of the Israeli component of the Survey of Health, Ageing, and Retirement in Europe (SHARE-Israel), 297 older adults reported ongoing exposure to missile attacks due to the Israel-Gaza conflict (mean age = 66.97), while 309 older adults reported exposure to an intense period of missile attacks during the Second Lebanon War (mean age = 66.63). Participants completed measures of PTSD symptoms, and physical, cognitive, and mental health. Older adults with ongoing exposure reported higher PTSD symptom level relative to those with intense time-limited exposure. The groups also differed in health variables related to PTSD symptoms. Namely, impaired physical and cognitive health were related to a higher level of PTSD symptoms in ongoing exposure, while impaired mental health was related to a higher PTSD symptom level following intense time-limited exposure. The findings suggest that physical and cognitive health involves resources that are vital for daily survival when living under ongoing warfare threat, whereas mental health involves resources that are needed in dealing with psychological effects of warfare trauma. Accordingly, different interventions may be necessary when helping older adults exposed to ongoing versus intense time-limited trauma.

The spatial patterns of directional phenotypic selection.

PubMed

Siepielski, Adam M; Gotanda, Kiyoko M; Morrissey, Michael B; Diamond, Sarah E; DiBattista, Joseph D; Carlson, Stephanie M

2013-11-01

Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

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

Xu, Haitao, E-mail: xuhaitao@ecust.edu.cn; Gou, Yongxia; Ye, Jing

2016-05-15

Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadienemore » for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L){sub 2}(SCN){sub 2}]{sub ∝}. • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.« less

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

Factors that impact access to ongoing health care for First Nation children with a chronic condition.

PubMed

Coombes, Julieann; Hunter, Kate; Mackean, Tamara; Holland, Andrew J A; Sullivan, Elizabeth; Ivers, Rebecca

2018-06-14

Access to multidisciplinary health care services for First Nation children with a chronic condition is critical for the child's health and well-being, but disparities and inequality in health care systems have been almost impossible to eradicate for First Nation people globally. The objective of this review is to identify the factors that impact access and ongoing care for First Nation children globally with a chronic condition. An extensive systematic search was conducted of nine electronic databases to identify primary studies that explored factors affecting access to ongoing services for First Nation children with a chronic disease or injury. Due to the heterogeneity of included studies the Mixed Method Appraisal Tool (MMAT) was used to assess study quality. A total of six studies from Australia, New Zealand and Canada were identified and included in this review. Four studies applied qualitative approaches using in-depth semi structured interviews, focus groups and community fora. Two of the six studies used quantitative approaches. Facilitators included the utilisation of First Nation liaison workers or First Nation Health workers. Key barriers that emerged included lack of culturally appropriate health care, distance, language and cultural barriers, racism, the lack of incorporation of First Nation workers in services, financial difficulties and transport issues. There are few studies that have identified positive factors that facilitate access to health care for First Nation children. There is an urgent need to develop programs and processes to facilitate access to appropriate health care that are inclusive of the cultural needs of First Nation children.

Sexual selection explains sex-specific growth plasticity and positive allometry for sexual size dimorphism in a reef fish

PubMed Central

Walker, Stefan P. W.; McCormick, Mark I.

2009-01-01

In 1950, Rensch noted that in clades where males are the larger sex, sexual size dimorphism (SSD) tends to be more pronounced in larger species. This fundamental allometric relationship is now known as ‘Rensch's rule’. While most researchers attribute Rensch's rule to sexual selection for male size, experimental evidence is lacking. Here, we suggest that ultimate hypotheses for Rensch's rule should also apply to groups of individuals and that individual trait plasticity can be used to test those hypotheses experimentally. Specifically, we show that in the sex-changing fish Parapercis cylindrica, larger males have larger harems with larger females, and that SSD increases with harem size. Thus, sexual selection for male body size is the ultimate cause of sexual size allometry. In addition, we experimentally illustrate a positive relationship between polygyny potential and individual growth rate during sex change from female to male. Thus, sexual selection is the ultimate cause of variation in growth rate, and variation in growth rate is the proximate cause of sexual size allometry. Taken together, our results provide compelling evidence in support of the sexual selection hypothesis for Rensch's rule and highlight the potential importance of individual growth modification in the shaping of morphological patterns in Nature. PMID:19553253

77 FR 15818 - License Renewal Interim Staff Guidance LR-ISG-2011-05: Ongoing Review of Operating Experience

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

...-05: Ongoing Review of Operating Experience AGENCY: Nuclear Regulatory Commission. ACTION: Interim... License Renewal Interim Staff Guidance (LR-ISG), LR-ISG-2011-05, ``Ongoing Review of Operating Experience... industry-wide operating experience as an attribute of aging management programs used at nuclear power...

The course of posttraumatic stress symptoms and functional impairment following a disaster: what is the lasting influence of acute vs. ongoing traumatic events and stressors?

PubMed Central

Cerdá, M.; Bordelois, P.M.; Galea, S.; Norris, F.; Tracy, M.; Koenen, K.C.

2012-01-01

Purpose Ongoing traumatic events and stressors, rather than acute sources of trauma, may shape long-term post-disaster mental health. The purpose of this study was to compare the influence of acute hurricane-related exposures and ongoing post-hurricane exposures on the short- and long-term course of posttraumatic stress symptoms (PTSS) and functional impairment (FI). Methods A random sample of adults (n=658) in Galveston and Chambers Counties, Texas, was selected 2–6 months after Hurricane Ike and interviewed 3 times over eighteen months. Hurricane-related exposures included traumatic events such as death of a family member due to the hurricane and stressors such as loss/damage to personal property due to the hurricane. Post-hurricane exposures included traumatic events such as sexual assault and stressors such as divorce or serious financial problems. Results Experiencing an acute hurricane-related traumatic event or stressor was associated with initial post-hurricane PTSS [RR=1.92(95% CI=1.13–3.26) and RR=1.62(1.36–1.94), respectively] and FI [RR=1.76; (1.05–2.97) and RR=1.74(1.46–2.08)], respectively, and acute hurricane-related stressors were associated with a higher rate of increase in FI over time [RR=1.09; (1.01–1.19)]. In contrast, ongoing post-hurricane daily stressors were not associated within initial PTSS and FI, but were associated with PTSS and FI at the second and third interviews. Conclusions While immediate postdisaster interventions may influence short-term mental health, investment in the prevention of ongoing stressors may be instrumental to manage long-term mental health status. PMID:22878832

Identifying signatures of positive selection in pigmentation genes in two South Asian populations.

PubMed

Jonnalagadda, Manjari; Bharti, Neeraj; Patil, Yatish; Ozarkar, Shantanu; K, Sunitha Manjari; Joshi, Rajendra; Norton, Heather

2017-09-10

Skin pigmentation is a polygenic trait showing wide phenotypic variations among global populations. While numerous pigmentation genes have been identified to be under positive selection among European and East populations, genes contributing to phenotypic variation in skin pigmentation within and among South Asian populations are still poorly understood. The present study uses data from the Phase 3 of the 1000 genomes project focusing on two South Asian populations-GIH (Gujarati Indian from Houston, Texas) and ITU (Indian Telugu from UK), so as to decode the genetic architecture involved in adaptation to ultraviolet radiation in South Asian populations. Statistical tests included were (1) tests to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), (2) tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb), and (3) tests based on genetic differentiation between populations (LSBL). Twenty-two pigmentation genes fall in the top 1% for at least one statistic in the GIH population, 5 of which (LYST, OCA2, SLC24A5, SLC45A2, and TYR) have been previously associated with normal variation in skin, hair, or eye color. In comparison, 17 genes fall in the top 1% for at least one statistic in the ITU population. Twelve loci which are identified as outliers in the ITU scan were also identified in the GIH population. These results suggest that selection may have affected these loci broadly across the region. © 2017 Wiley Periodicals, Inc.

Eotaxin/CCL11 expression by infiltrating macrophages in rat heart transplants during ongoing acute rejection.

PubMed

Zweifel, Martin; Mueller, Christoph; Schaffner, Thomas; Dahinden, Clemens; Matozan, Katja; Driscoll, Robert; Mohacsi, Paul

2009-10-01

Eotaxin/CCL11 chemokine is expressed in different organs, including the heart, but its precise cellular origin in the heart is unknown. Eotaxin is associated with Th2-like responses and exerts its chemotactic effect through the chemokine receptor-3 (CCR3), which is also expressed on mast cells (MC). The aim of our study was to find the cellular origin of eotaxin in the heart, and to assess whether expression is changing during ongoing acute heart transplant rejection, indicating a correlation with mast cell infiltration which we observed in a previous study. In a model of ongoing acute heart transplant rejection in the rat, we found eotaxin mRNA expression within infiltrating macrophages, but not in mast cells, by in situ-hybridization. A five-fold increase in eotaxin protein in rat heart transplants during ongoing acute rejection was measured on day 28 after transplantation, compared to native and isogeneic control hearts. Eotaxin concentrations in donor hearts on day 28 after transplantation were significantly higher compared to recipient hearts, corroborating an origin of eotaxin from cells within the heart, and not from the blood. The quantitative comparison of eotaxin mRNA expression between native hearts, isografts, and allografts, respectively, revealed no statistically significant difference after transplantation, probably due to an overall increase in the housekeeping gene's 18S rRNA during rejection. Quantitative RT-PCR showed an increase in mRNA expression of CCR3, the receptor for eotaxin, during ongoing acute rejection of rat heart allografts. Although a correlation between increasing eotaxin expression by macrophages and mast cell infiltration is suggestive, functional studies will elucidate the role of eotaxin in the process of ongoing acute heart transplant rejection.

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

PubMed Central

McDivitt, Maxine E.; Topp, Eleanor B.

1964-01-01

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

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.

A Collaborative, Ongoing University Strategic Planning Framework: Process, Landmines, and Lessons

ERIC Educational Resources Information Center

Hill, Susan E. Kogler; Thomas, Edward G.; Keller, Lawrence F.

2009-01-01

This article examines the strategic planning process at Cleveland State University, a large metropolitan state university in Ohio. A faculty-administrative team used a communicative planning approach to develop a collaborative, ongoing, bottom-up, transparent strategic planning process. This team then spearheaded the process through plan…

Augmenting the Genetic Toolbox for Sulfolobus islandicus with a Stringent Positive Selectable Marker for Agmatine Prototrophy

PubMed Central

Cooper, Tara E.; Krause, David J.

2013-01-01

Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176

Ongoing Relative Performance Evaluation for a CO2 EOR Asset in a Worldwide Peer Group

NASA Astrophysics Data System (ADS)

Zhao, C. F.; Li, X. S.; Wang, G. H.; Li, L.

2017-10-01

Abstract. Operators of a CO2 EOR asset need to know the relative performance level of their asset against its peers. The ongoing relative performance evaluation method is appropriate for this purpose. We first choose 52 CO2 assets around the world as the peer group, and then define the four ranking levels in terms of CO2consumption ratio. Only the final values of CO2consumption ratio for the group are obtained, and therefore cannot be used for an ongoing evaluation during a CO2 EOR asset’s life circle. Consequently, numerical reservoir simulation is employed to quantify the process values corresponding to the four ranking levels. Type curve plots are generated on the basis of the process values and utilized for the ongoing relative performance evaluation of a CO2 EOR asset in China.

Selection Criteria for Patients With Chronic Ankle Instability in Controlled Research: A Position Statement of the International Ankle Consortium

PubMed Central

Gribble, Phillip A.; Delahunt, Eamonn; Bleakley, Christopher M.; Caulfield, Brian; Docherty, Carrie L.; Fong, Daniel Tik-Pui; Fourchet, François; Hertel, Jay; Hiller, Claire E.; Kaminski, Thomas W.; McKeon, Patrick O.; Refshauge, Kathryn M.; van der Wees, Philip; Vicenzino, William; Wikstrom, Erik A.

2014-01-01

ABSTRACT While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant or patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient or participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient. PMID:24377963

Stakeholders, Networks and Links in Early Childhood Policy: Network Analysis and the "Transition to School: Position Statement"

ERIC Educational Resources Information Center

Wallis, Jake; Dockett, Sue

2015-01-01

The importance of a positive start to school has been highlighted in a range of national and international research. This has stimulated considerable ongoing research attention, as well as initiatives across policy and practice, all with the aim of promoting a positive transition to school for all children. Despite the common interests across…

The Role of Parents in the College Selection Process.

ERIC Educational Resources Information Center

Buford, Delores

This study of parents' role in the college selection process is part of an ongoing market research agenda at a small, private, liberal arts college. Data were gathered from parents of currently enrolled freshmen about the information they needed to make informed decisions about which school their child would attend and the information they…

Pipe degradation investigations for optimization of flow-accelerated corrosion inspection location selection

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

Chandra, S.; Habicht, P.; Chexal, B.

1995-12-01

A large amount of piping in a typical nuclear power plant is susceptible to Flow-Accelerated Corrosion (FAC) wall thinning to varying degrees. A typical PAC monitoring program includes the wall thickness measurement of a select number of components in order to judge the structural integrity of entire systems. In order to appropriately allocate resources and maintain an adequate FAC program, it is necessary to optimize the selection of components for inspection by focusing on those components which provide the best indication of system susceptibility to FAC. A better understanding of system FAC predictability and the types of FAC damage encounteredmore » can provide some of the insight needed to better focus and optimize the inspection plan for an upcoming refueling outage. Laboratory examination of FAC damaged components removed from service at Northeast Utilities` (NU) nuclear power plants provides a better understanding of the damage mechanisms involved and contributing causes. Selected results of this ongoing study are presented with specific conclusions which will help NU to better focus inspections and thus optimize the ongoing FAC inspection program.« less

25 CFR 1000.396 - Does a Tribe/Consortium have additional ongoing requirements to maintain minimum standards for...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 2 2013-04-01 2013-04-01 false Does a Tribe/Consortium have additional ongoing requirements to maintain minimum standards for Tribe/Consortium management systems? 1000.396 Section 1000.396... Miscellaneous Provisions § 1000.396 Does a Tribe/Consortium have additional ongoing requirements to maintain...

Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015.

PubMed

Ruppitsch, Werner; Prager, Rita; Halbedel, Sven; Hyden, Patrick; Pietzka, Ariane; Huhulescu, Steliana; Lohr, Dorothee; Schönberger, Katharina; Aichinger, Elisabeth; Hauri, Anja; Stark, Klaus; Vygen, Sabine; Tietze, Erhard; Allerberger, Franz; Wilking, Hendrik

2015-01-01

Listeriosis patient isolates in Germany have shown a new identical pulsed-field gel electrophoresis (PFGE) pattern since 2012 (n = 66). Almost all isolates (Listeria monocytogenes serotype 1/2a) belonged to cases living in southern Germany, indicating an outbreak with a so far unknown source. Case numbers in 2015 are high (n = 28). No outbreak cases outside Germany have been reported. Next generation sequencing revealed the unique cluster type CT1248 and confirmed the outbreak. Investigations into the source are ongoing.

A light-up probe with aggregation-induced emission characteristics (AIE) for selective imaging, naked-eye detection and photodynamic killing of Gram-positive bacteria.

PubMed

Feng, Guangxue; Yuan, Youyong; Fang, Hu; Zhang, Ruoyu; Xing, Bengang; Zhang, Guanxin; Zhang, Deqing; Liu, Bin

2015-08-11

We report the design and synthesis of a red fluorescent AIE light-up probe for selective recognition, naked-eye detection, and image-guided photodynamic killing of Gram-positive bacteria, including vancomycin-resistant Enterococcus strains.

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.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-01-01

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

Phylodynamic Analysis of Clinical and Environmental Vibrio cholerae Isolates from Haiti Reveals Diversification Driven by Positive Selection

PubMed Central

Azarian, Taj; Ali, Afsar; Johnson, Judith A.; Mohr, David; Prosperi, Mattia; Veras, Nazle M.; Jubair, Mohammed; Strickland, Samantha L.; Rashid, Mohammad H.; Alam, Meer T.; Weppelmann, Thomas A.; Katz, Lee S.; Tarr, Cheryl L.; Colwell, Rita R.

2014-01-01

ABSTRACT Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. PMID:25538191

An approach for filtering hyperbolically positioned underwater acoustic telemetry data with position precision estimates

USGS Publications Warehouse

Meckley, Trevor D.; Holbrook, Christopher M.; Wagner, C. Michael; Binder, Thomas R.

2014-01-01

The use of position precision estimates that reflect the confidence in the positioning process should be considered prior to the use of biological filters that rely on a priori expectations of the subject’s movement capacities and tendencies. Position confidence goals should be determined based upon the needs of the research questions and analysis requirements versus arbitrary selection, in which filters of previous studies are adopted. Data filtering with this approach ensures that data quality is sufficient for the selected analyses and presents the opportunity to adjust or identify a different analysis in the event that the requisite precision was not attained. Ignoring these steps puts a practitioner at risk of reporting errant findings.

Thymopentin treatment of selective IgA deficiency.

PubMed

Fiorilli, M; Quinti, I; Russi, G; Seminara, R; Ensoli, B; Aiuti, F

1985-01-01

Thymic hormones have been shown to modulate immunoglobulin production in a number of experiments and it is generally agreed that this action is mediated by modulation of helper and/or suppressor T cell activities. The possibility of upregulating the immunoglobulins is of particular relevance in patients with hypogammaglobulinemias and this paper reports on the results of thymopentin treatment in 9 patients with selective IgA deficiency. Two out of 4 patients responded positively in an open-label trial; in one the serum IgA values remained stable up to 8 weeks after discontinuation of treatment whereas there was a rapid fall in the other. Both responders had consistently normal T4/T8 ratios during the treatment, whereas the nonresponders revealed high ratios with large fluctuations of the T4/T8 ratio. In a subsequent (still ongoing) double-blind trial in 5 patients (3 thymopentin, 2 placebo) no significant change of serum or secretory IgA levels has been observed. Taken together, the data suggest that the tested dose regimen of thymopentin (i.e. daily i.m. injections of 1 mg/kg for 2 weeks, then same dose 3 time weekly for 10 weeks) may only work in a subset of patients with selective IgA deficiency. In the present study we did not attempt to distinguish to which of the three known subgroups the 9 patients belonged, nor did we try alternative dose regimens of thymopentin.

Hormone activation induces nucleosome positioning in vivo

PubMed Central

Belikov, Sergey; Gelius, Birgitta; Almouzni, Geneviève; Wrange, Örjan

2000-01-01

The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone. PMID:10698943

Dealing with prospective memory demands while performing an ongoing task: Shared processing, increased on-task focus, or both?

PubMed

Rummel, Jan; Smeekens, Bridget A; Kane, Michael J

2017-07-01

Prospective memory (PM) is the cognitive ability to remember to fulfill intended action plans at the appropriate future moment. Current theories assume that PM fulfillment draws on attentional processes. Accordingly, pending PM intentions interfere with other ongoing tasks to the extent to which both tasks rely on the same processes. How do people manage the competition between PM and ongoing-task demands? Based on research relating mind wandering and attentional control (Kane & McVay, 2012), we argue that people may not only change the way they process ongoing-task stimuli when given a PM intention, but they may also engage in less off-task thinking than they otherwise would. That is, people focus more strongly on the tasks at hand and dedicate considerable conscious thought to the PM goal. We tested this hypothesis by asking subjects to periodically report on their thoughts during prototypical PM (and control) tasks. Task-unrelated thought rates dropped when participants performed an ongoing task while holding a PM intention versus performing the ongoing task alone (Experiment 1), even when PM demands were minimized (Experiment 2) and more so when PM execution was especially rewarded (Experiment 3). Our findings suggest that PM demands not only elicit a cost to ongoing-task processing, but they also induce a stronger on-task focus and promote conscious thoughts about the PM intention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-July 7, 2016.

PubMed

Adams, Laura; Bello-Pagan, Melissa; Lozier, Matthew; Ryff, Kyle R; Espinet, Carla; Torres, Jomil; Perez-Padilla, Janice; Febo, Mitchelle Flores; Dirlikov, Emilio; Martinez, Alma; Munoz-Jordan, Jorge; Garcia, Myriam; Segarra, Marangely Olivero; Malave, Graciela; Rivera, Aidsa; Shapiro-Mendoza, Carrie; Rosinger, Asher; Kuehnert, Matthew J; Chung, Koo-Whang; Pate, Lisa L; Harris, Angela; Hemme, Ryan R; Lenhart, Audrey; Aquino, Gustavo; Zaki, Sherif; Read, Jennifer S; Waterman, Stephen H; Alvarado, Luisa I; Alvarado-Ramy, Francisco; Valencia-Prado, Miguel; Thomas, Dana; Sharp, Tyler M; Rivera-Garcia, Brenda

2016-08-05

Zika virus is a flavivirus transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes, and infection can be asymptomatic or result in an acute febrile illness with rash (1). Zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects (2). Infection has also been associated with Guillain-Barré syndrome (GBS) (3) and severe thrombocytopenia (4,5). In December 2015, the Puerto Rico Department of Health (PRDH) reported the first locally acquired case of Zika virus infection. This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico (6,7). A confirmed case of Zika virus infection is defined as a positive result for Zika virus testing by reverse transcription-polymerase chain reaction (RT-PCR) for Zika virus in a blood or urine specimen. A presumptive case is defined as a positive result by Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (MAC-ELISA)* and a negative result by dengue virus IgM ELISA, or a positive test result by Zika IgM MAC-ELISA in a pregnant woman. An unspecified flavivirus case is defined as positive or equivocal results for both Zika and dengue virus by IgM ELISA. During November 1, 2015-July 7, 2016, a total of 23,487 persons were evaluated by PRDH and CDC Dengue Branch for Zika virus infection, including asymptomatic pregnant women and persons with signs or symptoms consistent with Zika virus disease or suspected GBS; 5,582 (24%) confirmed and presumptive Zika virus cases were identified. Persons with Zika virus infection were residents of 77 (99%) of Puerto Rico's 78 municipalities. During 2016, the percentage of positive Zika virus infection cases among symptomatic males and nonpregnant females who were tested increased from 14% in February to 64% in June. Among 9,343 pregnant women tested, 672 had confirmed or presumptive Zika virus infection, including 441 (66%) symptomatic women and 231 (34%) asymptomatic

Consequences of ongoing civil conflict in Somalia: evidence for public health responses.

PubMed

Guha-Sapir, Debarati; Ratnayake, Ruwan

2009-08-01

Debarati Guha-Sapir and Ruwan Ratnayake use field data to demonstrate the severe vulnerability faced by much of the Somalian population due to ongoing conflict, and call for concerted public health interventions and access to food aid especially in southern Somalia.

Prestin and the cholinergic receptor of hair cells: positively-selected proteins in mammals

PubMed Central

Elgoyhen, Ana Belén; Franchini, Lucía F.

2010-01-01

The hair cells of the vertebrate inner ear posses active mechanical processes to amplify their inputs. The stereocilia bundle of various vertebrate animals can produce active movements. Though standard stereocilia-based mechanisms to promote amplification persist in mammals, an additional radically different mechanism evolved: the so called somatic electromotility which refers to the elongation/contraction of the outer hair cells’ (OHC) cylindrical cell body in response to membrane voltage changes. Somatic electromotility in OHCs, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon the properties of the unique motor protein prestin. We review recent literature which has demonstrated that although the gene encoding prestin is present in all vertebrate species, mammalian prestin has been under positive selective pressure to acquire motor properties, probably rendering it fit to serve somatic motility in outer hair cells. Moreover, we discuss data which indicates that a modified α10 nicotinic cholinergic receptor subunit has coevolved in mammals, most likely to give the auditory feedback system the capability to control somatic electromotility. PMID:20056140

Put on Your Dancing Shoes! Choreographing Positive Partnerships with Parents of Gifted Children.

ERIC Educational Resources Information Center

Riley, Tracy L.

1999-01-01

Uses the analogy of dance to discuss development of positive relationships between teachers and parents of gifted children. Emphasis is on providing parents with necessary information, overcoming barriers to true partnerships, and rules of thumb for implementing the partnership on an ongoing basis, such as following the golden rule in…

Assessing the Impact of Ongoing National Terror: Social Workers in Israel

ERIC Educational Resources Information Center

Ron, Pnina; Shamai, Michal

2011-01-01

The main goal of this study was to explore the connections between social workers' personal and professional exposure to national terror in Israel and their professional and personal distress experienced due to ongoing terror attacks. Data were collected from 406 social workers from Israel who worked in agencies that provide help to victims of…

From Further to Higher Education: Transition as an On-Going Process

ERIC Educational Resources Information Center

Tett, Lyn; Cree, Viviene E; Christie, Hazel

2017-01-01

This paper argues that transition is not a one-off event that occurs when students first enter universities but is an on-going process that is repeated over time. We draw on qualitative data from a longitudinal project on "non-traditional" students who entered a research-intensive university in Scotland direct from further education…

Aftershocks of Chile's Earthquake for an Ongoing, Large-Scale Experimental Evaluation

ERIC Educational Resources Information Center

Moreno, Lorenzo; Trevino, Ernesto; Yoshikawa, Hirokazu; Mendive, Susana; Reyes, Joaquin; Godoy, Felipe; Del Rio, Francisca; Snow, Catherine; Leyva, Diana; Barata, Clara; Arbour, MaryCatherine; Rolla, Andrea

2011-01-01

Evaluation designs for social programs are developed assuming minimal or no disruption from external shocks, such as natural disasters. This is because extremely rare shocks may not make it worthwhile to account for them in the design. Among extreme shocks is the 2010 Chile earthquake. Un Buen Comienzo (UBC), an ongoing early childhood program in…

Immune Checkpoint Inhibition in Hepatocellular Carcinoma: Basics and Ongoing Clinical Trials.

PubMed

Kudo, Masatoshi

2017-01-01

Clinical trials of antibodies targeting the immune checkpoint inhibitors programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for the treatment of advanced hepatocellular carcinoma (HCC) are ongoing. Expansion cohorts of a phase I/II trial of the anti-PD-1 antibody nivolumab in advanced HCC showed favorable results. Two phase III studies are currently ongoing: a comparison of nivolumab and sorafenib in the first-line setting for advanced HCC, and a comparison of the anti-PD-1 antibody pembrolizumab and a placebo in the second-line setting for patients with advanced HCC who progressed on sorafenib therapy. The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. Immune checkpoint inhibitors may therefore open new doors to the treatment of HCC. © 2017 S. Karger AG, Basel.

An ongoing six-year innovative osteoporosis disease management program: challenges and success in an IPA physician group environment.

PubMed

Woo, Ann; Hittell, Jodi; Beardsley, Carrie; Noh, Charles; Stoukides, Cheryl A; Kaul, Alan F

2004-01-01

The goal of this ongoing comprehensive osteoporosis disease management initiative is to provide the adult primary care physicians' (PCPs) offices with a program enabling them to systematically identify and manage their population for osteoporosis. For over six years, Hill Physicians Medical Group (Hill Physicians) has implemented multiple strategies to develop a best practice for identifying and treating members who were candidates for osteoporosis therapy. Numerous tools were used to support this disease management effort, including: evidence-based clinical practice guidelines, patient education sessions, the Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire tool, member specific reports for PCPs, targeted member mailings, office-based Peripheral Instantaneous X-ray Imaging (PIXI) test and counseling, dual x-ray absorptiometry (DEXA) scan guidelines, and web-based Electronic Simple Calculated Osteoporosis Risk Estimation (eSCORE) questionnaire tools. Hill Physicians tabulated results for patients who completed 2649 SCORE tests, screened 978 patients with PIXI tests, and identified 338 osteopenic and 124 osteoporotic patients. The preliminary results of this unique six-year ongoing educational initiative are slow but promising. New physician offices express interest in participating and those offices that have participated in the program continue to screen for osteoporosis. Hill Physicians' message is consistent and is communicated to the physicians repeatedly in different ways in accordance with the principles of educational outreach. Physicians who have conducted the program have positive feedback from their patients and office staff and have begun to communicate their experience to their peers.

The facilitating effect of positive emotions during an emotional Stroop task.

PubMed

Liu, Xingyu; Yang, Yisheng; Jiang, Songxiu; Li, Jie

2018-05-08

Prior research has shown that negative emotions, even though task irrelevant, are capable of delaying a participant's response to the color in which a negative emotional word is presented, a phenomenon known as the 'emotional Stroop effect'. However, relatively little is known about whether positive emotions have a similar or an opposite effect. The current study sets out to confirm the facilitating effect of positive emotions on color naming, which is predicted by Barbara Fredrickson's 'broaden and build' theory. Our results indicate that positive emotions did facilitate such processing in both of the study's experiments. We also found a significant difference in early posterior negativity amplitudes between positive and neutral stimuli, which was related to the 'fast effect'. Overall, the study's findings suggest that positive emotions can be detected quickly and automatically, and that this kind of prioritizing facilitates the ongoing cognitive processing.

EXPOSURE TO DIESEL EXHAUST ENHANCES THE SEVERITY OF AN ONGOING INFLUENZA INFECTION.

EPA Science Inventory

Numerous studies have shown that air pollutants including diesel exhaust (DE), alter host defense responses to decrease resistance to respiratory infection. The purpose of this study was to evaluate the effects of DE exposure on the severity of an ongoing influenza infection in ...

Social phobia and selective mutism.

PubMed

Keeton, Courtney P; Crosby Budinger, Meghan

2012-07-01

Social phobia (SOP) and selective mutism (SM) are related anxiety disorders characterized by distress and dysfunction in social situations. SOP typically onsets in adolescence and affects about 8% of the general population, whereas SM onsets before age 5 and is prevalent in up to 2% of youth. Prognosis includes a chronic course that confers risk for other disorders or ongoing social disability, but more favorable outcomes may be associated with young age and low symptom severity. SOP treatments are relatively more established, whereas dissemination of promising and innovative SM-treatment strategies is needed.

Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.

PubMed

Gribble, Phillip A; Delahunt, Eamonn; Bleakley, Chris; Caulfield, Brian; Docherty, Carrie; Fourchet, François; Fong, Daniel Tik-Pui; Hertel, Jay; Hiller, Claire; Kaminski, Thomas; McKeon, Patrick; Refshauge, Kathryn; van der Wees, Philip; Vincenzino, Bill; Wikstrom, Erik

2014-07-01

While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

Self-Leadership Change Project: The Continuation of an Ongoing Experiential Program

ERIC Educational Resources Information Center

Phillips, James I.; Kern, Dave; Tewari, Jitendra; Jones, Kenneth E.; Beemraj, Eshwar Prasad; Ettigi, Chaitra Ashok

2017-01-01

Purpose: The self-leadership change project (SLCP) is an ongoing program for senior level students at a regional university designed to provide hands-on experience in building self-management skills, which is considered a pre-requisite by many leaders and scholars (e.g. Drucker, 1996; Schaetti et al., 2008). The paper aims to discuss this issue.…

Using two on-going HIV studies to obtain clinical data from before, during and after pregnancy for HIV-positive women.

PubMed

Huntington, Susie E; Bansi, Loveleen K; Thorne, Claire; Anderson, Jane; Newell, Marie-Louise; Taylor, Graham P; Pillay, Deenan; Hill, Teresa; Tookey, Pat A; Sabin, Caroline A

2012-07-28

The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone. Women in UK CHIC receiving HIV-clinical care in 1996-2009, were found in the NSHPC dataset by initially 'linking' records with identical date-of-birth, linked records were then accepted as a genuine 'match', if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively). Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.

Differential effects of ongoing EEG beta and theta power on memory formation

PubMed Central

Scholz, Sebastian; Schneider, Signe Luisa

2017-01-01

Recently, elevated ongoing pre-stimulus beta power (13–17 Hz) at encoding has been associated with subsequent memory formation for visual stimulus material. It is unclear whether this activity is merely specific to visual processing or whether it reflects a state facilitating general memory formation, independent of stimulus modality. To answer that question, the present study investigated the relationship between neural pre-stimulus oscillations and verbal memory formation in different sensory modalities. For that purpose, a within-subject design was employed to explore differences between successful and failed memory formation in the visual and auditory modality. Furthermore, associative memory was addressed by presenting the stimuli in combination with background images. Results revealed that similar EEG activity in the low beta frequency range (13–17 Hz) is associated with subsequent memory success, independent of stimulus modality. Elevated power prior to stimulus onset differentiated successful from failed memory formation. In contrast, differential effects between modalities were found in the theta band (3–7 Hz), with an increased oscillatory activity before the onset of later remembered visually presented words. In addition, pre-stimulus theta power dissociated between successful and failed encoding of associated context, independent of the stimulus modality of the item itself. We therefore suggest that increased ongoing low beta activity reflects a memory promoting state, which is likely to be moderated by modality-independent attentional or inhibitory processes, whereas high ongoing theta power is suggested as an indicator of the enhanced binding of incoming interlinked information. PMID:28192459

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

PubMed

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

2016-03-01

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

24 CFR 35.1355 - Ongoing lead-based paint maintenance and reevaluation activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Ongoing lead-based paint...

24 CFR 35.1355 - Ongoing lead-based paint maintenance and reevaluation activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Ongoing lead-based paint...

24 CFR 35.1355 - Ongoing lead-based paint maintenance and reevaluation activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Ongoing lead-based paint...

24 CFR 35.1355 - Ongoing lead-based paint maintenance and reevaluation activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Secretary, Department of Housing and Urban Development LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Methods and Standards for Lead-Paint Hazard Evaluation and Hazard Reduction Activities... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Ongoing lead-based paint...

Positive interventions: An emotion regulation perspective.

PubMed

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

2015-05-01

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

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia.

PubMed

Liu, Xuanyao; Yunus, Yushimah; Lu, Dongsheng; Aghakhanian, Farhang; Saw, Woei-Yuh; Deng, Lian; Ali, Mohammad; Wang, Xu; Nor, Fadzilah Mohd; Ghazali, Fadzilah; Rahman, Thuhairah Abdul; Shaari, Shahrul Azlin; Salleh, Mohd Zaki; Phipps, Maude E; Ong, Rick Twee-Hee; Xu, Shuhua; Teo, Yik-Ying; Hoh, Boon-Peng

2015-04-01

The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

Ongoing Speciation and Gene Flow between Taxonomically Challenging Trochulus Species Complex (Gastropoda: Hygromiidae).

PubMed

Proćków, Małgorzata; Strzała, Tomasz; Kuźnik-Kowalska, Elżbieta; Proćków, Jarosław; Mackiewicz, Paweł

2017-01-01

Geographical isolation, selection and genetic drift can cause the geographical diversification of populations and lead to speciation. Land snail species in the genus Trochulus show overlaps in geographical ranges as well as in morphology, but genetic data do not always support the species-level taxonomy based on morphological characters. Such a group offers an excellent opportunity to explore the processes involved. We have addressed the problem by determining the status of the restricted endemic T. graminicola within the larger context of Trochulus taxonomy. We used an integrated approach based on morphological features, ecological preferences and two molecular markers: mitochondrial COI sequences and microsatellites. Comparison of these results demonstrated: (i) conchological distinction of T. striolatus and T. sericeus; (ii) anatomical, ecological and genetic differentiation of T. graminicola and (iii) concordance between morphological characters and mtDNA markers in T. striolatus. Moreover, our data showed an intricate evolutionary history within the genus Trochulus, which can be best explained by: (i) recent or ongoing gene flow between taxa or (ii) their large ancestral polymorphism. Both of these hypotheses suggest that diversification within this group of snails has occurred relatively recently. The mismatches between species defined on morphology and on molecular genetics indicate the complexity of the processes involved in the diversification of this genus.

Ongoing Speciation and Gene Flow between Taxonomically Challenging Trochulus Species Complex (Gastropoda: Hygromiidae)

PubMed Central

Proćków, Małgorzata; Strzała, Tomasz; Kuźnik-Kowalska, Elżbieta; Proćków, Jarosław; Mackiewicz, Paweł

2017-01-01

Geographical isolation, selection and genetic drift can cause the geographical diversification of populations and lead to speciation. Land snail species in the genus Trochulus show overlaps in geographical ranges as well as in morphology, but genetic data do not always support the species-level taxonomy based on morphological characters. Such a group offers an excellent opportunity to explore the processes involved. We have addressed the problem by determining the status of the restricted endemic T. graminicola within the larger context of Trochulus taxonomy. We used an integrated approach based on morphological features, ecological preferences and two molecular markers: mitochondrial COI sequences and microsatellites. Comparison of these results demonstrated: (i) conchological distinction of T. striolatus and T. sericeus; (ii) anatomical, ecological and genetic differentiation of T. graminicola and (iii) concordance between morphological characters and mtDNA markers in T. striolatus. Moreover, our data showed an intricate evolutionary history within the genus Trochulus, which can be best explained by: (i) recent or ongoing gene flow between taxa or (ii) their large ancestral polymorphism. Both of these hypotheses suggest that diversification within this group of snails has occurred relatively recently. The mismatches between species defined on morphology and on molecular genetics indicate the complexity of the processes involved in the diversification of this genus. PMID:28107432

Ongoing hydrothermal activities within Enceladus

NASA Astrophysics Data System (ADS)

Hsu, Hsiang-Wen; Postberg, Frank; Sekine, Yasuhito; Shibuya, Takazo; Kempf, Sascha; Horányi, Mihály; Juhász, Antal; Altobelli, Nicolas; Suzuki, Katsuhiko; Masaki, Yuka; Kuwatani, Tatsu; Tachibana, Shogo; Sirono, Sin-Iti; Moragas-Klostermeyer, Georg; Srama, Ralf

2015-03-01

Detection of sodium-salt-rich ice grains emitted from the plume of the Saturnian moon Enceladus suggests that the grains formed as frozen droplets from a liquid water reservoir that is, or has been, in contact with rock. Gravitational field measurements suggest a regional south polar subsurface ocean of about 10 kilometres thickness located beneath an ice crust 30 to 40 kilometres thick. These findings imply rock-water interactions in regions surrounding the core of Enceladus. The resulting chemical `footprints' are expected to be preserved in the liquid and subsequently transported upwards to the near-surface plume sources, where they eventually would be ejected and could be measured by a spacecraft. Here we report an analysis of silicon-rich, nanometre-sized dust particles (so-called stream particles) that stand out from the water-ice-dominated objects characteristic of Saturn. We interpret these grains as nanometre-sized SiO2 (silica) particles, initially embedded in icy grains emitted from Enceladus' subsurface waters and released by sputter erosion in Saturn's E ring. The composition and the limited size range (2 to 8 nanometres in radius) of stream particles indicate ongoing high-temperature (>90 °C) hydrothermal reactions associated with global-scale geothermal activity that quickly transports hydrothermal products from the ocean floor at a depth of at least 40 kilometres up to the plume of Enceladus.

Explaining the apparent paradox of persistent selection for early flowering.

PubMed

Austen, Emily J; Rowe, Locke; Stinchcombe, John R; Forrest, Jessica R K

2017-08-01

Decades of observation in natural plant populations have revealed pervasive phenotypic selection for early flowering onset. This consistent pattern seems at odds with life-history theory, which predicts stabilizing selection on age and size at reproduction. Why is selection for later flowering rare? Moreover, extensive evidence demonstrates that flowering time can and does evolve. What maintains ongoing directional selection for early flowering? Several non-mutually exclusive processes can help to reconcile the apparent paradox of selection for early flowering. We outline four: selection through other fitness components may counter observed fecundity selection for early flowering; asymmetry in the flowering-time-fitness function may make selection for later flowering hard to detect; flowering time and fitness may be condition-dependent; and selection on flowering duration is largely unaccounted for. In this Viewpoint, we develop these four mechanisms, and highlight areas where further study will improve our understanding of flowering-time evolution. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

A strategy for position-selective epoxidation of polyprenols.

PubMed

Gnanadesikan, Vijay; Corey, E J

2008-06-25

An effective strategy has been developed for the efficient site-selective epoxidation of poylolefinic isoprenoid alcohols, based on the use of an internal control element for intramolecular reaction. The approach is illustrated by application to a series of polyisoprenoid alcohols (polyprenols) at substrate concentration of 0.5 mM. With polyprenol substrates having the hydroxyl function at one terminus, the internal epoxidation can be directed at the double bond of the polyprenol, which is either four or five away from the terminal hydroxyprenyl subunit.

A SURVEY OF EPA/OPP AND OPEN LITERATURE ON SELECTED PESTICIDE CHEMICALS III. MUTAGENICITY AND CARCINOGENICITY OF BENOMYL AND CARBENDAZIM

EPA Science Inventory

Abstract
The known aneuploidogens, benomyl and its metabolite, carbendazim (methyl 2- benzimidazole carbamate or MBC), were selected for the third in a series of ongoing projects with selected pesticides. Mutagenicity and carcinogenicity data submitted to the U.S. Environmen...

Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy.

PubMed

Xie, Jennifer Y; Qu, Chaoling; Patwardhan, Amol; Ossipov, Michael H; Navratilova, Edita; Becerra, Lino; Borsook, David; Porreca, Frank

2014-08-01

Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically, including gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1 day after incision) or neuropathic (14 days after spinal nerve ligation [SNL]) pain to determine whether the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups, and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain, produced increased NAc DA in rats with SNL but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional but not neuropathic pain. Increased extracellular NAc DA release was consistent with CPP and was observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

An ongoing process: a qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence.

PubMed

Yeh, Mei-Yu; Che, Hui-Lian; Wu, Shu-Mei

2009-11-24

Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services.

An ongoing process: A qualitative study of how the alcohol-dependent free themselves of addiction through progressive abstinence

PubMed Central

2009-01-01

Background Most people being treated for alcoholism are unable to successfully quit drinking within their treatment programs. In few cases do we know the full picture of how abstinence is achieved in Taiwan. We tracked processes of abstinence in alcohol-dependency disorders, based on study evidence and results. This research explores the process of recovery from the viewpoint of the alcohol-dependent. Methods Semi-structured interviews were conducted in two different settings, using purpose sampling, during 2003-2004. The data were analyzed using content analysis. Participants were 32 adults, purposefully selected from an Alcoholics Anonymous group and a psychiatric hospital in North Taiwan. Results We found that the abstinence process is an ongoing process, in which the alcohol-dependent free themselves of addiction progressively. This process never ends or resolves in complete recovery. We have identified three stages in the struggle against alcoholism: the Indulgence, Ambivalence and Attempt (IAA) cycle, in which the sufferer is trapped in a cycle of attempting to give up and failing; the Turning Point, in which a Personal Nadir is reached, and the Ongoing Process of abstinence, in which a constant effort is made to remain sober through willpower and with the help of support groups. We also discuss Influencing Factors that can derail abstinence attempts, pushing the sufferer back into the IAA cycle. Conclusion This study provides important points of reference for alcohol and drug service workers and community healthcare professionals in Taiwan, casting light on the abstinence process and providing a basis for intervention or rehabilitation services. PMID:19930698

New evidence for positive selection helps explain the paternal age effect observed in achondroplasia

PubMed Central

Shinde, Deepali N.; Elmer, Dominik P.; Calabrese, Peter; Boulanger, Jérôme; Arnheim, Norman; Tiemann-Boege, Irene

2013-01-01

There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10−6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism. PMID:23740942

Natural Selection in the Great Apes

PubMed Central

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

2016-01-01

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

Quality Matters™: An Educational Input in an Ongoing Design-Based Research Project

ERIC Educational Resources Information Center

Adair, Deborah; Shattuck, Kay

2015-01-01

Quality Matters (QM) has been transforming established best practices and online education-based research into an applicable, scalable course level improvement process for the last decade. In this article, the authors describe QM as an ongoing design-based research project and an educational input for improving online education.

Binaural frequency selectivity in humans.

PubMed

Verhey, Jesko L; van de Par, Steven

2018-01-23

Several behavioural studies in humans have shown that listening to sounds with two ears that is binaural hearing, provides the human auditory system with extra information on the sound source that is not available when sounds are only perceived through one ear that is monaurally. Binaural processing involves the analysis of phase and level differences between the two ear signals. As monaural cochlea processing (in each ear) precedes the neural stages responsible for binaural processing properties it is reasonable to assume that properties of the cochlea may also be observed in binaural processing. A main characteristic of cochlea processing is its frequency selectivity. In psychoacoustics, there is an ongoing discussion on the frequency selectivity of the binaural auditory system. While some psychoacoustic experiments seem to indicate poorer frequency selectivity of the binaural system than that of the monaural processing others seem to indicate the same frequency selectivity for monaural and binaural processing. This study provides an overview of these seemingly controversial results and the different explanations that were provided to account for the different results. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Natural positive selection and north-south genetic diversity in East Asia.

PubMed

Suo, Chen; Xu, Haiyan; Khor, Chiea-Chuen; Ong, Rick Th; Sim, Xueling; Chen, Jieming; Tay, Wan-Ting; Sim, Kar-Seng; Zeng, Yi-Xin; Zhang, Xuejun; Liu, Jianjun; Tai, E-Shyong; Wong, Tien-Yin; Chia, Kee-Seng; Teo, Yik-Ying

2012-01-01

Recent reports have identified a north-south cline in genetic variation in East and South-East Asia, but these studies have not formally explored the basis of these clinical differences. Understanding the origins of these variations may provide valuable insights in tracking down the functional variants in genomic regions identified by genetic association studies. Here we investigate the genetic basis of these differences with genome-wide data from the HapMap, the Human Genome Diversity Project and the Singapore Genome Variation Project. We implemented four bioinformatic measures to discover genomic regions that are considerably differentiated either between two Han Chinese populations in the north and south of China, or across 22 populations in East and South-East Asia. These measures prioritized genomic stretches with: (i) regional differences in the allelic spectrum for SNPs common to the two Han Chinese populations; (ii) differential evidence of positive selection between the two populations as quantified by integrated haplotype score (iHS) and cross-population extended haplotype homozygosity (XP-EHH); (iii) significant correlation between allele frequencies and geographical latitudes of the 22 populations. We also explored the extent of linkage disequilibrium variations in these regions, which is important in combining genetic association studies from North and South Chinese. Two of the regions that emerged are found in HLA class I and II, suggesting that the HLA imputation panel from the HapMap may not be directly applicable to every Chinese sample. This has important implications to autoimmune studies that plan to impute the classical HLA alleles to fine map the SNP association signals.

Natural positive selection and north–south genetic diversity in East Asia

PubMed Central

Suo, Chen; Xu, Haiyan; Khor, Chiea-Chuen; Ong, Rick TH; Sim, Xueling; Chen, Jieming; Tay, Wan-Ting; Sim, Kar-Seng; Zeng, Yi-Xin; Zhang, Xuejun; Liu, Jianjun; Tai, E-Shyong; Wong, Tien-Yin; Chia, Kee-Seng; Teo, Yik-Ying

2012-01-01

Recent reports have identified a north–south cline in genetic variation in East and South-East Asia, but these studies have not formally explored the basis of these clinical differences. Understanding the origins of these variations may provide valuable insights in tracking down the functional variants in genomic regions identified by genetic association studies. Here we investigate the genetic basis of these differences with genome-wide data from the HapMap, the Human Genome Diversity Project and the Singapore Genome Variation Project. We implemented four bioinformatic measures to discover genomic regions that are considerably differentiated either between two Han Chinese populations in the north and south of China, or across 22 populations in East and South-East Asia. These measures prioritized genomic stretches with: (i) regional differences in the allelic spectrum for SNPs common to the two Han Chinese populations; (ii) differential evidence of positive selection between the two populations as quantified by integrated haplotype score (iHS) and cross-population extended haplotype homozygosity (XP-EHH); (iii) significant correlation between allele frequencies and geographical latitudes of the 22 populations. We also explored the extent of linkage disequilibrium variations in these regions, which is important in combining genetic association studies from North and South Chinese. Two of the regions that emerged are found in HLA class I and II, suggesting that the HLA imputation panel from the HapMap may not be directly applicable to every Chinese sample. This has important implications to autoimmune studies that plan to impute the classical HLA alleles to fine map the SNP association signals. PMID:21792231

Molecular Population Genetics of Human CYP3A Locus: Signatures of Positive Selection and Implications for Evolutionary Environmental Medicine

PubMed Central

Chen, Xiaoping; Wang, Haijian; Zhou, Gangqiao; Zhang, Xiumei; Dong, Xiaojia; Zhi, Lianteng; Jin, Li; He, Fuchu

2009-01-01

Background The human CYP3A gene cluster codes for cytochrome P450 (CYP) subfamily enzymes that catalyze the metabolism of various exogenous and endogenous chemicals and is an obvious candidate for evolutionary and environmental genomic study. Functional variants in the CYP3A locus may have undergone a selective sweep in response to various environmental conditions. Objective The goal of this study was to profile the allelic structure across the human CYP3A locus and investigate natural selection on that locus. Methods From the CYP3A locus spanning 231 kb, we resequenced 54 genomic DNA fragments (a total of 43,675 bases) spanning four genes (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) and two pseudogenes (CYP3AP1 and CYP3AP2), and randomly selected intergenic regions at the CYP3A locus in Africans (24 individuals), Caucasians (24 individuals), and Chinese (29 individuals). We comprehensively investigated the nucleotide diversity and haplotype structure and examined the possible role of natural selection in shaping the sequence variation throughout the gene cluster. Results Neutrality tests with Tajima’s D, Fu and Li’s D* and F*, and Fay and Wu’s H indicated possible roles of positive selection on the entire CYP3A locus in non-Africans. Sliding-window analyses of nucleotide diversity and frequency spectrum, as well as haplotype diversity and phylogenetically inferred haplotype structure, revealed that CYP3A4 and CYP3A7 had recently undergone or were undergoing a selective sweep in all three populations, whereas CYP3A43 and CYP3A5 were undergoing a selective sweep in non-Africans and Caucasians, respectively. Conclusion The refined allelic architecture and selection spectrum for the human CYP3A locus highlight that evolutionary dynamics of molecular adaptation may underlie the phenotypic variation of the xenobiotic disposition system and varied predisposition to complex disorders in which xenobiotics play a role. PMID:20019904

Dietary patterns and the phenotype of polycystic ovary syndrome: the chance of ongoing pregnancy.

PubMed

Huijgen, Nicole A; Louwers, Yvonne V; Willemsen, Sten P; de Vries, Jeanne H M; Steegers-Theunissen, Régine P M; Laven, Joop S E

2017-06-01

Polycystic ovary syndrome (PCOS) is generally considered a complex disorder caused by interactions between genetic and environmental factors. In a sub-cohort of women with PCOS visiting the preconception outpatient clinic of a tertiary hospital with follow-up in a periconception cohort, we identified specific dietary patterns and adherence in patients with PCOS with and without hyperandrogenism and the chance of ongoing pregnancy. Food frequency questionnaires were available from 55 patients diagnosed with PCOS during follow-up in routine clinical practice, including 25 with hyperandrogenism and 30 without hyperandrogenism. Strong adherence to the healthy dietary pattern was inversely associated with the hyperandrogenic PCOS phenotype (Adjusted OR 0.27; 95% CI 0.07 to 0.99). In women with PCOS overall, a strong adherence to the healthy dietary pattern showed a three-fold higher chance of ongoing pregnancy (adjusted OR 3.38; 95% CI 1.01 to 11.36) and an association with anti-Müllerian hormone concentration (β -0.569 µg/L; 95% CI -0.97 to -0.17). The effect of this dietary pattern on the chance of ongoing pregnancy and AMH suggests causality, which needs further investigation in prospective studies in the general population. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Initial and Ongoing Teacher Preparation and Support: Current Problems and Possible Solutions

ERIC Educational Resources Information Center

Johnson, Harold A.

2013-01-01

The effective initial preparation and ongoing support of teachers of students who are deaf and hard of hearing has always been a difficult and controversial task. Changes in student demographic characteristics and educational settings, combined with the rapidly diminishing number and diversity of deaf education teacher preparation (DETP) programs,…

Shared and Unique Components of Human Population Structure and Genome-Wide Signals of Positive Selection in South Asia

PubMed Central

Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-01-01

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. PMID:22152676

Prospective Memory Deficits in Ecstasy Users: Effects of Longer Ongoing Task Delay Interval

PubMed Central

WEINBORN, MICHAEL; WOODS, STEVEN PAUL; NULSEN, CLAIRE; PARK, KATHERINE

2011-01-01

Ecstasy use has been associated with neurotoxicity and neurocognitive impairment in a variety of domains, including prospective memory (ProM), which involves the delayed execution of a previously encoded intention in response to a specific cue. The present study adopted the multiprocess theory of ProM to evaluate the hypothesis that ecstasy users would evidence differentially impaired ProM on longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk alcohol users (n = 21) and healthy nonusers (n = 31) completed the short (2-min) and long (15-min) delay ProM scales of the Memory for Intentions Screening Test. Results showed a significant group by ProM delay interaction, such that ecstasy users performed comparably to the comparison groups on short-delay trials, but were impaired on long-delay ProM, particularly for time-based cues. Among the ecstasy users, long-delay ProM was positively associated with risky decision-making, but not with retrospective memory or other aspects of executive functions. These findings suggest that ecstasy users may be particularly susceptible to deficits in strategic target monitoring and maintenance of cue-intention pairings over longer ProM delays. Findings are discussed in the context of their potential everyday functioning (e.g., academic, vocational) and treatment implications for ecstasy users. PMID:22047194

Development of practice principles for the management of ongoing suicidal ideation in young people diagnosed with major depressive disorder.

PubMed

Rice, Simon M; Simmons, Magenta B; Bailey, Alan P; Parker, Alexandra G; Hetrick, Sarah E; Davey, Christopher G; Phelan, Mark; Blaikie, Simon; Edwards, Jane

2014-01-01

There is a lack of clear guidance regarding the management of ongoing suicidality in young people experiencing major depressive disorder. This study utilised an expert consensus approach in identifying practice principles to complement relevant clinical guidelines for the treatment of major depressive disorder in young people. The study also sought to outline a broad treatment framework for clinical intervention with young people experiencing ongoing suicidal ideation. In-depth focus groups were undertaken with a specialist multidisciplinary clinical team (the Youth Mood Clinic at Orygen Youth Health Clinical Program, Melbourne) working with young people aged 15-25 years experiencing ongoing suicidal ideation. Each focus group was audio recorded and transcribed verbatim using orthographic conventions. Principles of grounded theory and thematic analysis were used to analyse and code the resultant data. The identified codes were subsequently synthesised into eight practice principles reflecting engagement and consistency of care, ongoing risk assessment and documentation, individualised crisis planning, engaging systems of support, engendering hopefulness, development of adaptive coping, management of acute risk, and consultation and supervision. The identified practice principles provide a broad management framework, and may assist to improve treatment consistency and clinical management of young people experiencing ongoing suicidal ideation. The practice principles may be of use to health professionals working within a team-based setting involved in the provision of care, even if peripherally, to young people with ongoing suicidal ideation. Findings address the lack of treatment consistency and shared terminology and may provide containment and guidance to multidisciplinary clinicians working with this at-risk group.

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

PubMed

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

2014-01-01

Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important

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.

Duplication and concerted evolution in a master sex determiner under balancing selection.

PubMed

Privman, Eyal; Wurm, Yannick; Keller, Laurent

2013-05-07

The transformer (tra) gene is a key regulator in the signalling hierarchy controlling all aspects of somatic sexual differentiation in Drosophila and other insects. Here, we show that six of the seven sequenced ants have two copies of tra. Surprisingly, the two paralogues are always more similar within species than among species. Comparative sequence analyses indicate that this pattern is owing to the ongoing concerted evolution after an ancestral duplication rather than independent duplications in each of the six species. In particular, there was strong support for inter-locus recombination between the paralogues of the ant Atta cephalotes. In the five species where the location of paralogues is known, they are adjacent to each other in four cases and separated by only few genes in the fifth case. Because there have been extensive genomic rearrangements in these lineages, this suggests selection acting to conserve their synteny. In three species, we also find a signature of positive selection in one of the paralogues. In three bee species where information is available, the tra gene is also duplicated, the copies are adjacent and in at least one species there was recombination between paralogues. These results suggest that concerted evolution plays an adaptive role in the evolution of this gene family.

Constraints on the richness-mass relation and the optical-SZE positional offset distribution for SZE-selected clusters

DOE PAGES

Saro, A.

2015-10-12

In this study, we cross-match galaxy cluster candidates selected via their Sunyaev–Zel'dovich effect (SZE) signatures in 129.1 deg 2 of the South Pole Telescope 2500d SPT-SZ survey with optically identified clusters selected from the Dark Energy Survey science verification data. We identify 25 clusters between 0.1 ≲ z ≲ 0.8 in the union of the SPT-SZ and redMaPPer (RM) samples. RM is an optical cluster finding algorithm that also returns a richness estimate for each cluster. We model the richness λ-mass relation with the following function 500> ∝ B λlnM 500 + C λlnE(z) and use SPT-SZ cluster masses andmore » RM richnesses λ to constrain the parameters. We find B λ = 1.14 +0.21 –0.18 and C λ = 0.73 +0.77 –0.75. The associated scatter in mass at fixed richness is σ lnM|λ = 0.18 +0.08 –0.05 at a characteristic richness λ = 70. We demonstrate that our model provides an adequate description of the matched sample, showing that the fraction of SPT-SZ-selected clusters with RM counterparts is consistent with expectations and that the fraction of RM-selected clusters with SPT-SZ counterparts is in mild tension with expectation. We model the optical-SZE cluster positional offset distribution with the sum of two Gaussians, showing that it is consistent with a dominant, centrally peaked population and a subdominant population characterized by larger offsets. We also cross-match the RM catalogue with SPT-SZ candidates below the official catalogue threshold significance ξ = 4.5, using the RM catalogue to provide optical confirmation and redshifts for 15 additional clusters with ξ ϵ [4, 4.5].« less

CRANE POSITIONING APPARATUS

DOEpatents

Landsiedel, F.W.; Wolff, H.

1960-06-28

An apparatus is described for automatically accomplishing the final accurate horizontal positioning of a crane after the latter has been placed to within 1/8 in. of its selected position. For this purpose there is provided a tiltable member on the crane mast for lowering into contact with a stationary probe. Misalignment of the tiltable member, with respect to the probe as the member is lowered, causes tilting of the latter to actuate appropriate switches that energize motors for bringing the mast into proper position. When properly aligned the member is not tilted and a central switch is actuated to indicate the final alignment of the crane.

Planned and ongoing projects (pop) database: development and results.

PubMed

Wild, Claudia; Erdös, Judit; Warmuth, Marisa; Hinterreiter, Gerda; Krämer, Peter; Chalon, Patrice

2014-11-01

The aim of this study was to present the development, structure and results of a database on planned and ongoing health technology assessment (HTA) projects (POP Database) in Europe. The POP Database (POP DB) was set up in an iterative process from a basic Excel sheet to a multifunctional electronic online database. The functionalities, such as the search terminology, the procedures to fill and update the database, the access rules to enter the database, as well as the maintenance roles, were defined in a multistep participatory feedback loop with EUnetHTA Partners. The POP Database has become an online database that hosts not only the titles and MeSH categorizations, but also some basic information on status and contact details about the listed projects of EUnetHTA Partners. Currently, it stores more than 1,200 planned, ongoing or recently published projects of forty-three EUnetHTA Partners from twenty-four countries. Because the POP Database aims to facilitate collaboration, it also provides a matching system to assist in identifying similar projects. Overall, more than 10 percent of the projects in the database are identical both in terms of pathology (indication or disease) and technology (drug, medical device, intervention). In addition, approximately 30 percent of the projects are similar, meaning that they have at least some overlap in content. Although the POP DB is successful concerning regular updates of most national HTA agencies within EUnetHTA, little is known about its actual effects on collaborations in Europe. Moreover, many non-nationally nominated HTA producing agencies neither have access to the POP DB nor can share their projects.

Chiral Selective Chemistry Induced by Natural Selection of Spin-Polarized Electrons.

PubMed

Rosenberg, Richard A; Mishra, Debabrata; Naaman, Ron

2015-06-15

The search to understand the origin of homochirality in nature has been ongoing since the time of Pasteur. Previous work has shown that DNA can act as a spin filter for low-energy electrons and that spin-polarized secondary electrons produced by X-ray irradiation of a magnetic substrate can induce chiral selective chemistry. In the present work it is demonstrated that secondary electrons from a substrate that are transmitted through a chiral overlayer cause enantiomeric selective chemistry in an adsorbed adlayer. We determine the quantum yields (QYs) for dissociation of (R)- or (S)-epichlorohydrin adsorbed on a chiral self-assembled layer of DNA on gold and on bare gold (for control). The results show that there is a significant difference in the QYs between the two enantiomers when adsorbed on DNA, but none when they are adsorbed on bare Au. We propose that the effect results from natural spin filtering effects cause by the chiral monolayer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlling Working Memory Operations by Selective Gating: The Roles of Oscillations and Synchrony

PubMed Central

Dipoppa, Mario; Szwed, Marcin; Gutkin, Boris S.

2016-01-01

Working memory (WM) is a primary cognitive function that corresponds to the ability to update, stably maintain, and manipulate short-term memory (ST M) rapidly to perform ongoing cognitive tasks. A prevalent neural substrate of WM coding is persistent neural activity, the property of neurons to remain active after having been activated by a transient sensory stimulus. This persistent activity allows for online maintenance of memory as well as its active manipulation necessary for task performance. WM is tightly capacity limited. Therefore, selective gating of sensory and internally generated information is crucial for WM function. While the exact neural substrate of selective gating remains unclear, increasing evidence suggests that it might be controlled by modulating ongoing oscillatory brain activity. Here, we review experiments and models that linked selective gating, persistent activity, and brain oscillations, putting them in the more general mechanistic context of WM. We do so by defining several operations necessary for successful WM function and then discussing how such operations may be carried out by mechanisms suggested by computational models. We specifically show how oscillatory mechanisms may provide a rapid and flexible active gating mechanism for WM operations. PMID:28154616

Controlling Working Memory Operations by Selective Gating: The Roles of Oscillations and Synchrony.

PubMed

Dipoppa, Mario; Szwed, Marcin; Gutkin, Boris S

2016-01-01

Working memory (WM) is a primary cognitive function that corresponds to the ability to update, stably maintain, and manipulate short-term memory (ST M) rapidly to perform ongoing cognitive tasks. A prevalent neural substrate of WM coding is persistent neural activity , the property of neurons to remain active after having been activated by a transient sensory stimulus. This persistent activity allows for online maintenance of memory as well as its active manipulation necessary for task performance. WM is tightly capacity limited. Therefore, selective gating of sensory and internally generated information is crucial for WM function. While the exact neural substrate of selective gating remains unclear, increasing evidence suggests that it might be controlled by modulating ongoing oscillatory brain activity. Here, we review experiments and models that linked selective gating, persistent activity, and brain oscillations, putting them in the more general mechanistic context of WM. We do so by defining several operations necessary for successful WM function and then discussing how such operations may be carried out by mechanisms suggested by computational models. We specifically show how oscillatory mechanisms may provide a rapid and flexible active gating mechanism for WM operations.

GI-POP: a combinational annotation and genomic island prediction pipeline for ongoing microbial genome projects.

PubMed

Lee, Chi-Ching; Chen, Yi-Ping Phoebe; Yao, Tzu-Jung; Ma, Cheng-Yu; Lo, Wei-Cheng; Lyu, Ping-Chiang; Tang, Chuan Yi

2013-04-10

Sequencing of microbial genomes is important because of microbial-carrying antibiotic and pathogenetic activities. However, even with the help of new assembling software, finishing a whole genome is a time-consuming task. In most bacteria, pathogenetic or antibiotic genes are carried in genomic islands. Therefore, a quick genomic island (GI) prediction method is useful for ongoing sequencing genomes. In this work, we built a Web server called GI-POP (http://gipop.life.nthu.edu.tw) which integrates a sequence assembling tool, a functional annotation pipeline, and a high-performance GI predicting module, in a support vector machine (SVM)-based method called genomic island genomic profile scanning (GI-GPS). The draft genomes of the ongoing genome projects in contigs or scaffolds can be submitted to our Web server, and it provides the functional annotation and highly probable GI-predicting results. GI-POP is a comprehensive annotation Web server designed for ongoing genome project analysis. Researchers can perform annotation and obtain pre-analytic information include possible GIs, coding/non-coding sequences and functional analysis from their draft genomes. This pre-analytic system can provide useful information for finishing a genome sequencing project. Copyright © 2012 Elsevier B.V. All rights reserved.

Methadone maintenance patients show a selective deficit to reverse positive outcomes in drug-related conditions compared to medication free prolonged opiate abstinence.

PubMed

Levy-Gigi, Einat; Kéri, Szabolcs; Shapiro, Alla R; Sason, Anat; Adelson, Miriam; Peles, Einat

2014-11-01

Drug addiction is a chronic relapsing disease. Most users will relapse back to using drugs over and over again throughout their life. These relapses may become more frequent in the presence of contextual reminders. We aimed to examine associations between the ability to maintain a medication-free life-style and the capability to learn and reverse positive and negative stimulus-outcome associations in the presence of neutral and drug-related contextual reminders. We conducted a highly unique comparison of former opiate-dependent individuals who are either medication free or methadone maintenance patients for the last ten years. Groups were matched for age, gender and education. Participants were tested on a novel partial reversal paradigm, which tests the ability to acquire and reverse stimulus-outcome associations in neutral and drug-related context. Both groups were equally able to acquire and reverse positive and negative outcomes in conditions of neutral context. However, methadone maintenance patients showed a selective deficit in reversing the outcomes of positive stimulus in drug-related context. Hence, after learning a positive stimulus-outcome association in one drug-related context, methadone maintenance patients struggled to learn that the same stimulus predicts negative outcome when presented later in a different drug-related context. Methadone maintenance patients demonstrate a selective difficulty to learn negative outcomes when exposed to a drug, but not neutral, related environment. The results may reflect the core mechanisms of addiction and provide a possible explanation for the inability of methadone maintenance patients to illicit drug abuse without the need of agonist treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Intraocular lens power selection and positioning with and without intraoperative aberrometry.

PubMed

Hatch, Kathryn M; Woodcock, Emily C; Talamo, Jonathan H

2015-04-01

To determine the value of intraoperative aberrometry in cases of toric intraocular lens (IOL) implantation and positioning. In this non-randomized retrospective comparative trial, two groups of eyes underwent cataract extraction with toric IOL implantation: the aberrometry group (n = 37 eyes), where toric IOL power and alignment were determined before surgery with automated keratometry, standard optical biometry, and an online calculator and then refined using intraoperative aberrometry, and the toric calculator group (n = 27 eyes), where IOL selection was performed in a similar manner but without intraoperative aberrometry. The primary outcome measure was mean postoperative residual refractive astigmatism (RRA). Mean RRA measured at follow-up after surgery was 0.46 ± 0.42 and 0.68 ± 0.34 diopters (D) in the aberrometry and toric calculator groups, respectively (P = .0153). A 75% and 57% reduction in cylinder was noted between preoperative keratometric astigmatism and postoperative RRA in the aberrometry and toric calculator groups, respectively (P = .0027). RRA of 0.25 D or less, 0.50 D or less, 0.75 D or less, and 1.00 D or less was seen 38%, 78%, 86%, and 95% of the time, respectively, in the aberrometry group and 22%, 33%, 74%, and 89% of the time, respectively, in the toric calculator group. These data show that the chance of a patient being in a lower postoperative RRA range increased when intraoperative aberrometry was used (P = .0130). Patients undergoing cataract extraction with toric IOL placement aided by intraoperative aberrometry were 2.4 times more likely to have less than 0.50 D of RRA compared to standard methods. Copyright 2015, SLACK Incorporated.

The TRacking Adolescents' Individual Lives Survey (TRAILS): Design, Current Status, and Selected Findings

ERIC Educational Resources Information Center

Ormel, Johan; Oldehinkel, Albertine J.; Sijtsema, Jelle; van Oort, Floor; Raven, Dennis; Veenstra, Rene; Vollebergh, Wilma A. M.; Verhulst, Frank C.

2012-01-01

Objectives: The objectives of this study were as follows: to present a concise overview of the sample, outcomes, determinants, non-response and attrition of the ongoing TRacking Adolescents' Individual Lives Survey (TRAILS), which started in 2001; to summarize a selection of recent findings on continuity, discontinuity, risk, and protective…

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

PubMed

Andrews, T Daniel; Gojobori, Takashi

2004-01-01

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

Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

PubMed

Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

2011-12-09

South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

ARHGAP18 is a novel gene under positive natural selection that influences HbF levels in β-thalassaemia.

PubMed

He, Yunyan; Luo, Jianming; Chen, Yang; Zhou, Xiaoheng; Yu, Shanjuan; Jin, Ling; Xiao, Xuan; Jia, Siyuan; Liu, Qiang

2018-02-01

Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of β-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of β-thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with β-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with β-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Ρ = 5.1 × 10 -4 ). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in β-thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF.

Practical support aids addiction recovery: the positive identity model of change.

PubMed

Johansen, Ayna B; Brendryen, Håvar; Darnell, Farnad J; Wennesland, Dag K

2013-07-31

There is a need for studies that can highlight principles of addiction recovery. Because social relationships are involved in all change processes, understanding how social motivations affect the recovery process is vital to guide support programs. The objective was to develop a model of recovery by examining addicted individuals' social motivations through longitudinal assessment of non-professional support dyads. A qualitative, longitudinal study design was used, combining focus groups and in-depth interviews with addicted individuals and their sponsors. Data were analyzed using the principles of grounded theory: open coding and memos for conceptual labelling, axial coding for category building, and selective coding for theory building. The setting was an addiction recovery social support program in Oslo, Norway. The informants included nine adults affected by addiction, six sponsors, and the program coordinator. The participants were addicted to either alcohol (2), benzodiazepines (1), pain killers (1) or polydrug-use (5). The sponsors were unpaid, and had no history of addiction problems. Support perceived to be ineffective emerged in dyads with no operationalized goal, and high emotional availability with low degree of practical support. Support perceived to be effective was signified by the sponsor attending to power imbalance and the addict coming into position to help others and feel useful. The findings appear best understood as a positive identity-model of recovery, indicated by the pursuit of skill building relevant to a non-drug using identity, and enabled by the on-going availability of instrumental support. This produced situations where role reversals were made possible, leading to increased self-esteem. Social support programs should be based on a positive identity-model of recovery that enable the building of a life-sustainable identity.

Practical support aids addiction recovery: the positive identity model of change

PubMed Central

2013-01-01

Background There is a need for studies that can highlight principles of addiction recovery. Because social relationships are involved in all change processes, understanding how social motivations affect the recovery process is vital to guide support programs. Methods The objective was to develop a model of recovery by examining addicted individuals’ social motivations through longitudinal assessment of non-professional support dyads. A qualitative, longitudinal study design was used, combining focus groups and in-depth interviews with addicted individuals and their sponsors. Data were analyzed using the principles of grounded theory: open coding and memos for conceptual labelling, axial coding for category building, and selective coding for theory building. The setting was an addiction recovery social support program in Oslo, Norway. The informants included nine adults affected by addiction, six sponsors, and the program coordinator. The participants were addicted to either alcohol (2), benzodiazepines (1), pain killers (1) or polydrug-use (5). The sponsors were unpaid, and had no history of addiction problems. Results Support perceived to be ineffective emerged in dyads with no operationalized goal, and high emotional availability with low degree of practical support. Support perceived to be effective was signified by the sponsor attending to power imbalance and the addict coming into position to help others and feel useful. Conclusions The findings appear best understood as a positive identity-model of recovery, indicated by the pursuit of skill building relevant to a non-drug using identity, and enabled by the on-going availability of instrumental support. This produced situations where role reversals were made possible, leading to increased self-esteem. Social support programs should be based on a positive identity-model of recovery that enable the building of a life-sustainable identity. PMID:23898827

Ongoing calving-frontal dynamics of glaciers in the Northern Patagonia Icefield, Chile

NASA Astrophysics Data System (ADS)

Bown, F.; Rivera, A.; Burger, F.; Carrión, D.; Cisternas, S.; Gacitúa, G.; Pena, M.; Oberreuter, J.; Silva, R.; Uribe, J. A.; Wendt, A.; Zamora, R.

2013-05-01

Patagonian glaciers are increasingly contributing to the global-sea level rise due to negative mass balances in recent decades, in spite of moderated temperature and precipitation changes taking place in the region. The Austral Chilean glaciers retreat and thinning are strongly influenced by local topography and frontal characteristics, both playing a key role in disrupting glacier responses. One of the main ice bodies in this region is the Northern Patagonian Icefield ( NPI, 46S/73W, 3953 km2), a plateau from where tens of outlet glaciers have been inventoried. Many of these glaciers are ending at sea or freshwater lakes where they are calving. This calving feature is typically associated to non-climatic fluctuations characterized by abnormally-high and sudden retreat and other exacerbated behaviors such as ice flow acceleration and dynamical thinning. The main aim of this work is the study of recent calving dynamics of three glaciers of the NPI, in order to analyze similarities versus differences associated to their location, topographical constraints and bathymetry, among other features. With this aim, airborne LIDAR and radar surveys, as well as field trips were conducted to the area in year 2012 where several instruments and sensors were installed. The selected study sites were the NPI eastern side freshwater calving glaciers Colonia (47.19S/73.29W) and Nef (47.03S/73.27W), and the NPI western margin tidewater calving San Rafael glacier (46.70S/73.76W). With all the collected data, calving fluxes of 0.03 km3 a-1 and 0.08 km3 a-1 were detected at Glaciares Colonia and Nef respectively. At San Rafael, the calving flux was much higher (0.94 km3 a-1) mainly due to a deeper bathymetry near the glacier front, and very high velocities (10m d-1) compared to the eastern side glaciers. At Glaciar San Rafael the calving flux is very likely modulated by tidal components and local buoyancy conditions, while at the eastern glaciers, calving is a near marginal feature

Selection of Phototransduction Genes in Homo sapiens.

PubMed

Christopher, Mark; Scheetz, Todd E; Mullins, Robert F; Abràmoff, Michael D

2013-08-13

We investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level. SNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively. Six of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes. There is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.